acyclovir and Acquired-Immunodeficiency-Syndrome

Neurological complications of varicella-zoster virus (VZV) are infrequent and include various clinical pictures. The reactivation of VZV in patients with AIDS is generally associated with an acute and severe meningoencephalitis. We report the epidemiological, clinical and virological data from 11 consecutive patients with diagnosis of HIV/AIDS and central nervous system (CNS) involvement due to VZV. All patients were male and seropositive for HIV. The primary risk factor for HIV infection was unprotected sexual contact. The median of CD4 T cell count was 142 cells/µL. All of them presented signs and symptoms of meningoencephalitis. Six patients (54.5%) presented pleocytosis; they all showed high CSF protein concentrations with a median of 2.1 g/dL. Polymerase chain reaction of cerebrospinal fluid specimen was positive for VZV in all of them and they were treated with intravenous acyclovir at doses of 30/mg/kg/day for 21 days. Overall survival was 63% (7 of 11 patients). The four dead patients had low cellular counts in CSF, below the median of this parameter. VZV should be included among the opportunistic pathogens that can involve CNS with a diffuse and severe meningoencephalitis in patients with advanced HIV/AIDS disease.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Encephalitis, Varicella Zoster; Fatal Outcome; Herpesvirus 3, Human; HIV Seropositivity; Humans; Leukocytosis; Male; Middle Aged; Polymerase Chain Reaction; Risk Factors; Unsafe Sex; Young Adult

Over the last thirty years, epidemiologic and molecular studies indicate a strong and synergist relationship between the dual epidemics of herpes simplex type 2 (HSV-2) and HIV-1 infection. While prospective studies show that HSV-2 infection increases the risk for HIV-1 acquisition by 2- to 3-fold, HSV-2 suppression with standard prophylactic doses of HSV-2 therapy did not prevent HIV-1 acquisition. Reconciling these discrepancies requires understanding recent HSV-2 pathogenesis research, which indicates HSV-2 infection is not a latent infection with infrequent recurrence but a near constant state of reactivation and viral shedding which is not completely suppressed by standard antivirals. Because current antivirals do not prevent or fully suppress HSV-2 replication, priorities are HSV-2 vaccine development and antivirals that reach high concentrations in the genital mucosa and suppress the persistent genital inflammation associated with genital herpes reactivation in order to reduce the increased susceptibility to HIV-1 infection associated with HSV-2. HIV-1 and HSV-2 synergy is also seen among co-infected individuals who exhibit higher HIV-1 viral load compared to HSV-2 uninfected individuals. Standard HSV-2 therapy modestly lowers HIV-1 viral load and is associated with slower HIV-1 disease progression. A promising area of research is higher doses of HSV-2 suppressive therapy achieving a greater reduction in plasma HIV-1 RNA, which could translate to greater reductions in HIV-1 disease progression and infectiousness. However, many questions remain to be answered including potential effectiveness and cost-effectiveness of higher dose HSV-2 suppressive therapy. Mathematical models of HSV-2 and HIV-1 at a population level would be useful tools to estimate the potential impact and cost-effectiveness of higher dose HSV-2 suppressive therapy.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Dose-Response Relationship, Drug; Female; Herpes Genitalis; Herpesvirus 2, Human; HIV-1; Humans; Male; Risk Factors; Viral Load; Virus Replication; Virus Shedding

Herpes simplex virus (HSV) infections are among the infections most frequently encountered by humans. Two types of HSV infections have been identified-HSV-1, which usually causes orolabial disease, and HSV-2, which is associated more frequently with genital and newborn infections. Usually, HSV causes mild and self-limited disease of the mouth and lips or at genital sites. However, on occasion, the disease can be life-threatening. Such is the case with neonatal HSV infection and HSV infections of the central nervous system. Furthermore, in the immunocompromised host, severe infection has been encountered and is a source of morbidity. Even in the immunocompetent host, frequent recurrences, particularly those of the genital tract, can be debilitating. Because HSV does cause genital ulcerative disease, it is associated with an increased risk of acquiring a human immunodeficiency virus infection. During the past 2 decades, selective and specific inhibitors of HSV replication have been developed. These agents, acyclovir, valaciclovir, and famciclovir, all accelerate the events of healing and decrease the probability of excreting the virus when they are taken in a suppressive fashion. The long-term safety of acyclovir has been unequivocally established. Its prodrug, valaciclovir, and the prodrug of penciclovir, famciclovir, have not been used in practice as long and, therefore, less is known about these agents; however, neither is available as a pediatric formulation.

Topics: 2-Aminopurine; Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Adult; Antiviral Agents; Central Nervous System Viral Diseases; Child, Preschool; Drug Resistance, Viral; Famciclovir; Herpes Genitalis; Herpes Labialis; Herpes Simplex; Humans; Infant; Infant, Newborn; Injections, Intravenous; Simplexvirus; Valacyclovir; Valine; Virus Replication

Controlled trials suggest that acyclovir/valacyclovir can provide significant clinical benefits when used for prophylaxis in the immunocompromised host. These findings implicate herpesvirus(es) in the pathogenesis of complex medical conditions, including graft rejection and death. However, it is not known which of the 8 herpesviruses are important under particular circumstances. Prime candidates for triggering adverse outcomes are cytomegalovirus (CMV) in solid organ transplant recipients (causing rejection), CMV and human herpesvirus type 6 (HHV-6) in bone marrow transplant patients (causing marrow suppression), and herpes simplex virus, HHV-6, and CMV in AIDS patients (accelerating the rate of human immunodeficiency virus disease progression and death). Other diseases that may have a herpesvirus component or trigger susceptible antiviral agents include atherosclerosis and multiple sclerosis. In the future, clinicians should be alert to novel findings of randomized trials that may provide insight into the pathogenesis of these diseases and the contributions made by clinically silent herpesvirus infections.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Arteriosclerosis; Bone Marrow Transplantation; Clinical Trials as Topic; Disease Progression; Herpesviridae; Herpesviridae Infections; Humans; Multiple Sclerosis; Organ Transplantation; Postoperative Complications; Valacyclovir; Valine

An ever-increasing variety of antiviral medications are being used clinically for an array of viral infections ranging from hepatitis to HIV. Some of these medications, such as acyclovir and foscarnet, have significant nephrotoxicity, whereas others are associated only rarely with renal failure. The spectrum of renal lesions associated with antiviral nephrotoxicity suggests that these medications may cause renal failure by affecting tubular cells or glomeruli. In most instances of antiviral-related nephrotoxicity, discontinuation of the offending agent results in a rapid return to normal renal function.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Foscarnet; Humans; Immunoglobulins, Intravenous; Influenza, Human; Interferon Type I; Kidney; Recombinant Proteins; Reverse Transcriptase Inhibitors

Much controversy surrounds the use of antiretroviral drugs in HIV-infected patients. The many studies involving large numbers of patients that have been and are being conducted have raised as many questions as they have sought to answer. Given that no cure exists and that all clinically available drugs have only limited activity despite their high toxicity, the question of which drug (or combination of drugs) to use, and in whom, continues to vex both the clinician and the patient. Only three specific antiretroviral agents are currently licensed for use: zidovudine (ZDV), didanosine (dideoxyinosine, ddI) and zalcitabine (dideoxycytidine, ddC). This article reviews the major studies comparing the clinical efficacy of these drugs and the possible benefits of adding acyclovir to zidovudine therapy. The questions of when to begin antiretroviral therapy and the role of combination chemotherapy are discussed. Whenever possible, 'clinical' endpoints (death or clinical progression) are distinguished from 'softer' endpoints (surrogate markers of progression, such as the CD4 lymphocyte count) in the studies reviewed. Recommendations for the use of antiretroviral agents based on currently available published data are made.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Complex; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Didanosine; Drug Therapy, Combination; Drug Tolerance; HIV Infections; HIV-1; Humans; Zalcitabine; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Chickenpox; Cytomegalovirus Infections; Herpes Simplex; Humans

Persons with AIDS who have CD4+ counts < or = 100 and transplant patients, especially bone marrow allograft recipients, may experience clinically significant infections with acyclovir-resistant herpes simplex virus (HSV) or varicella-zoster virus (VZV). Patients who have received prior repeated acyclovir treatment appear to be at the highest risk of harboring acyclovir-resistant strains. Algorithms for the management of these infections were developed at a recent roundtable symposium. The consensus of the panelists was that treatment with foscarnet should be initiated within 7-10 days in patients suspected to have acyclovir-resistant HSV or VZV infections. Foscarnet therapy should be continued for at least 10 days or until lesions are completely healed.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Algorithms; Drug Resistance, Microbial; Female; Foscarnet; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Herpesvirus 3, Human; Humans; Immunocompromised Host; Male; Recurrence; Simplexvirus; Trifluridine; Vidarabine

The treatment of infectious complications in the cancer patient has evolved as a consequence of the developments in cancer chemotherapy, which significantly impair immune function. Broad-spectrum, single-agent antibiotics have replaced more cumbersome multidrug regimens for empiric coverage of fever and neutropenia in many institutions. The use of new, potent oral antibiotics may be a next step toward further simplifications. Several new antivirals have come into clinical use in the past decade, and reports of viral resistance to the standard agent, acyclovir, have come forth. Increasing experience with new (and older) antifungal and antiparasitic agents has given a better understanding of the use of these drugs for both prophylaxis and treatment. This overview includes a critical appraisal of the attributes and limitations of current antibiotics, antivirals, antifungals, and antiparasitic agents for the immunocompromised host.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Aminoglycosides; Amphotericin B; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Azoles; Aztreonam; Cephalosporins; Fluoroquinolones; Foscarnet; Ganciclovir; Humans; Imipenem; Immunocompromised Host; Infections; Neoplasms; Pneumonia, Pneumocystis; Vancomycin

Over the last few years we have seen the advent of effective antiviral drug therapy, the major ramifications being in the area of herpes infections. Acyclovir has become an established part of clinical practice, and other compounds are being increasingly used in the immunocompromised host. An effective vaccine is available for chickenpox, but herpes simplex and cytomegalovirus vaccines are still in early development. Thus, antiviral agents will continue to play a major role in the management of all herpesvirus infections for the foreseeable future. Current work includes the development of increased bioavailability prodrugs (BW 256, famciclovir), which are converted to active drug once absorbed, enabling rapid high serum levels, and hence may turn out to have increased efficacy in HSV- and VZV-induced diseases, for which oral acyclovir currently is the treatment of choice. Markedly increased efficacy against VZV in vitro has been demonstrated by two current agents under study (BVaraU, BW 882). HPMPC is now entering clinical trials with a markedly improved efficacy profile against CMV and HSV in animal models. Finally, drug combinations that are being investigated in AIDS may offer a means to avoid resistance in herpes infections in immunocompromised patients.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Animals; Antiviral Agents; Clinical Trials as Topic; Foscarnet; Ganciclovir; Herpesviridae Infections; Humans; Vidarabine

The nucleoside analog acyclovir is remarkably effective and selective in herpes simplex virus (HSF) infections. Acyclovir inhibits the viral enzyme DNA polymerase. Emergence of acyclovir-resistant HSV mutants occurs in immunocompromised patients, especially those with AIDS. Detection of HSV strains with resistance to antiviral drugs requires rapid in vitro tests to determine the IC50, i.e., the concentration of drug which inhibits viral replication by 50%. Studies of patterns of HSV resistance to the various antiviral agents used in medicine and characterization of mutant HSV strains have shown resistance to be due to loss or modification of the viral enzyme thymidine kinase or to changes in the viral DNA polymerase. The main clinically-significant acyclovir-resistant mutants are thymidine kinase-deficient and retain sensitivity to vidarabine and foscarnet. Development of resistance to both acyclovir and foscarnet due to changes in viral DNA polymerase is considerably less common but emphasizes the urgent need for new antiviral strategies for use in immunocompromised patients.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Opportunistic Infections; DNA-Directed DNA Polymerase; Drug Resistance, Microbial; Foscarnet; Herpes Simplex; In Vitro Techniques; Simplexvirus; Thymidine Kinase; Vidarabine

Resistance to acyclovir in vitro in herpes simplex virus (HSV) isolates has been associated with failure of acyclovir therapy in immunosuppressed patients, and the frequency of reports of clinical resistance in patients with human immunodeficiency virus (HIV) infection is increasing. The primary mechanism of clinical resistance is mutation, producing deficiency in the virus-specified thymidine kinase. A number of case reports and patient series have suggested the efficacy of foscarnet in the treatment of acyclovir-resistant HSV infection in HIV-infected patients. In a recent AIDS Clinical Trials Group study comparing the efficacy of vidarabine and foscarnet in this indication, foscarnet therapy was found to be associated with statistically significant reductions in time to complete healing of lesions, cessation of viral shedding, and 50% reduction in pain, and all patients randomized to receive foscarnet had complete re-epithelialization of lesions. The majority of initial recurrences of herpetic lesions in patients in this study were susceptible to acyclovir; however, all patients ultimately experienced a recurrence due to acyclovir-resistant HSV. A trial comparing acyclovir suppression, foscarnet maintenance therapy, and no chronic antiviral therapy after successful initial treatment of acyclovir-resistant HSV infection would be useful in defining the optimal management of recurrent disease.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Drug Resistance; Herpes Simplex; Humans

Current data about oral hairy leukoplakia are reported. Clinical manifestations, histological and ultrastructural features and pathogenic mechanisms are firstly described. Then diagnosis are exposed. Finally, management is discussed.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Herpesvirus 4, Human; Humans; Leukoplakia, Oral; Male; Tongue Diseases

The development of new antiviral agents has gained increasing momentum. It has kept pace with the identification of specific sites ("targets") in the virus replicative cycle at which potential antiviral drug can interact. The current armamentarium of available antiviral drugs consists of amantadine and rimantadine (against influenza A), ribavirin (against respiratory syncytial virus infection), idoxuridine and trifluridine (against herpetic keratitis), vidarabine and acyclovir (against herpes simplex virus infections), ganciclovir (against cytomegalovirus infections) and Retrovir (against AIDS). Various new compounds have been found which selectively inhibit those viruses [i.e. adenovirus, varicella-zoster virus, thymidine kinase-deficient (TK-) herpes simplex virus strains, and rhinoviruses] that are insensitive or poorly sensitive to the presently available antivirals. Several new compounds have also proven active against human immunodeficiency virus, the causative agent of AIDS; and, as a spin-off of the search for anti-AIDS drugs, new agents may also be expected that are effective against other retrovirus infections as well as hepadnavirus (i.e. hepatitis B virus) infections.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Chemical Phenomena; Chemistry; Cytomegalovirus Infections; Ganciclovir; Humans; Zidovudine

Though the reported experience with zidovudine in human pregnancies is very limited, it would seem unreasonable at this time to withhold zidovudine therapy for fetal considerations in the treatment of pregnant women with AIDS and ARC. Whether the treatment of HIV-positive women with zidovudine at any time during pregnancy reduces the risk of perinatal transmission is unknown. Therefore, the use of zidovudine for that indication should await the results of controlled trials. At present, if zidovudine therapy is required during pregnancy, the standard dosage of 200 mg every 4 hours should be used. The woman and her fetus should be monitored carefully for signs of toxicity.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Female; Humans; Pregnancy; Pregnancy Complications, Infectious; Virus Diseases; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Herpes Zoster; Humans; Immune Tolerance; Immunocompetence; Immunologic Deficiency Syndromes; Virus Replication

It appears that true otologic manifestations of AIDS are rare and that incidental otologic disease associated with AIDS is more common. A review of the literature revealed that otitis externa, acute otitis media, recurrent acute otitis media, otitis media with effusion, chronic suppurative otitis media with cholesteatoma, and herpes zoster oticus may all represent incidental otologic disease occurring in patients with AIDS. Chronic otitis media without cholesteatoma (P carinii-infected aural polyps), sensorineural hearing loss, acceleration of otosyphilis from the latent stage, and development of Kaposi's sarcoma of the external auricle or nasopharynx may represent true otologic manifestations of AIDS.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Ear Diseases; Humans; Interferon Type I; Opportunistic Infections; Penicillins; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Herpes Simplex; Humans; Vidarabine

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Cytomegalovirus Infections; Diabetic Retinopathy; Diagnosis, Differential; Foscarnet; Ganciclovir; Humans; Phosphonoacetic Acid; Pneumonia, Pneumocystis; Prognosis; Retinal Diseases; Retinitis; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Acyclovir; Chorioretinitis; Cytomegalovirus Infections; Diagnosis, Differential; Ganciclovir; Herpes Zoster Ophthalmicus; Humans; Keratitis, Dendritic; Light Coagulation; Mycoses; Necrosis; Opportunistic Infections; Retina; Retinitis; Syphilis; Toxoplasmosis

Viral pneumonitides are among the known pulmonary complications of human immunodeficiency virus (HIV) infection. Cytomegalovirus (CMV) pneumonitis is the most frequently recognized viral infection involving the lung. Although CMV may occasionally be the sole pathogen found to be responsible for severe pneumonitis in patients with the acquired immunodeficiency syndrome (AIDS), in most cases, its role in causing pulmonary disease is less clear, primarily because of the propensity to infect with a variety of other copathogens. CMV pneumonitis has been difficult to diagnose during life, although techniques utilizing in situ DNA hybridization or monoclonal antibodies for detection of the virus may improve the diagnostic yield of less invasive procedures such as bronchoalveolar lavage. Pneumonitis due to herpes simplex virus, varicella-zoster, and respiratory syncytial virus have occasionally been reported in AIDS patients, and are of practical importance because of the availability of effective treatment. The role of influenza and adenoviruses in causing HIV-related pulmonary complications is unknown, but could be of importance during outbreaks of these infections. Finally, data from several studies now suggest that Epstein-Barr virus or HIV itself or both have a role in the pneumonitis. Further study in this area could provide information leading to more effective management of this common complication of childhood AIDS.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Herpes Simplex; Herpesviridae Infections; Humans; Infectious Mononucleosis; Influenza, Human; Pneumonia, Viral; Retroviridae Infections

Serious disease due to cytomegalovirus (CMV) is almost totally confined to congenitally infected infants and the immunocompromised. Cell-mediated immunity is primarily responsible for the control of infection following primary infection and for prevention of disease after reactivation. In patients receiving active immunosuppression for transplantation, the choice of drug regimens is important in determining the likelihood of disseminated CMV infection and disease and it may be possible to control the infection by reducing the doses used. A number of strategies have been introduced in attempts to reduce the morbidity and mortality of CMV in the immunocompromised. These include prophylactic administration of specific immunoglobulin or acyclovir and the therapeutic use of several antiviral agents shown to have activity against CMV in vitro. Ganciclovir (DHPG) and foscarnet (phosphonoformate) have shown the most promise in clinical trials and ganciclovir has now been licensed for use in the UK, in sight- and life-threatening infections.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Immune Tolerance; Immunosuppression Therapy

CMV disease is a major problem in AIDS, though with a different profile from that seen in other immunosuppressed patients. The novel treatments, ganciclovir and phosphonoformate, have a major role in the management of such infections, but maintenance therapy is often required. Optimal maintenance regimens have yet to be established, especially where zidovudine is also being used.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Addison Disease; Antiviral Agents; Colitis; Cytomegalovirus Infections; Encephalitis; Esophageal Diseases; Foscarnet; Ganciclovir; Humans; Phosphonoacetic Acid; Pneumonia, Viral; Retinitis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Chickenpox; Child; Chronic Disease; Herpes Zoster; Herpesvirus 3, Human; Humans; Immune Tolerance; Neoplasms; Pneumonia, Viral

Life-threatening opportunistic cytomegalovirus infection is a complication of the acquired immunodeficiency syndrome (AIDS) that occurs in 7.4% or more of patients with AIDS. Cytomegalovirus retinitis, colitis, esophagitis, and gastritis are the commonest manifestations of severe cytomegalovirus end-organ disease. Extensive trials with intravenous ganciclovir, a nucleoside analogue with myelosuppressive toxicity, have shown that ganciclovir halts the progression of cytomegalovirus retinitis and gastrointestinal disease. Since relapse is common when therapy is discontinued, most patients with AIDS need life-long maintenance therapy. The clinical response to ganciclovir therapy is usually accompanied by diminished shedding of the virus. Based on limited data, foscarnet, a pyrophosphate analogue, also appears to have some efficacy in treating cytomegalovirus infection. Unlike ganciclovir, foscarnet does not cause myelosuppression. An important direction for future clinical research is the development of more effective and less toxic therapy, as well as orally bioavailable drugs for maintenance therapy.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Foscarnet; Ganciclovir; Gastroenteritis; Humans; Opportunistic Infections; Phosphonoacetic Acid; Pneumonia, Viral; Retinitis

Both oral and intravenous acyclovir administration for seven days in the early stages of infectious mononucleosis caused an inhibition of oropharyngeal Epstein-Barr virus (EBV) replication. Minimal effect on clinical symptoms was observed. Development of normal cellular and humoral EBV-specific immunity was seen in all patients. The combination of intravenous acyclovir and prednisolone treatment for 10 days in 11 patients with fulminant mononucleosis caused transient cessation of virus shedding in all patients. A dramatic clinical effect on pharyngeal symptoms and on fever was seen in nine of 11 patients within 72 hours. Treatment with chemotherapy or irradiation is recommended in EBV-associated B cell lymphomas seen in immunosuppressed, transplanted, and human immunodeficiency virus-I seropositive patients. No effect of acyclovir has been reported, but such therapy may be considered in the early stage when EBV induces a polyclonal B cell activation. Acyclovir treatment is effective in the EBV-genome positive hairy leukoplakia in human immunodeficiency virus-seropositive patients. No effect of antiviral therapy has been reported in the X-linked lymphoproliferative syndrome. Prophylactic use of immunoglobulin or acyclovir has been suggested in susceptible children.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Burkitt Lymphoma; Clinical Trials as Topic; Female; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immune Tolerance; Infectious Mononucleosis; Lymphoproliferative Disorders; Male; Prednisolone

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Animals; Bone Marrow Transplantation; Combined Modality Therapy; Cytomegalovirus Infections; Ganciclovir; Humans; Immunization, Passive; Opportunistic Infections; Pneumonia, Viral; Postoperative Complications

Immunosuppressed patients are at risk for developing cytomegalovirus retinitis. This disorder is the most common cause of vision loss in patients with the acquired immunodeficiency syndrome (AIDS). Cytomegalovirus retinitis is probably the result of hematogenous spread of the virus to the retina after systemic reactivation of a latent cytomegalovirus infection. Although the ophthalmic infection may initially be asymptomatic, the retinal necrosis it produces may result in both loss of visual field and decreased visual acuity. Routine screening of these patients is required for early diagnosis. The retinitis is detected with ophthalmoscopy as either a perivascular yellow-white retinal lesion frequently associated with retinal hemorrhage or as a focal white granular infiltrate, often without hemorrhage. Both lesions enlarge in a progressively expanding "brushfire" pattern. The diagnosis of cytomegalovirus retinitis, as well as the evaluation of its response to therapy, is determined primarily by clinical criteria. Serial retinal photography is an objective method to assess the changing appearance of these lesions. Ganciclovir and foscarnet are investigational antiviral drugs that appear to be effective in treating cytomegalovirus retinitis. However, maintenance therapy with these medications is required after initial treatment because the disease often relapses. The combined expertise of the internist and the ophthalmologist is needed to diagnose and treat these patients.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Diagnosis, Differential; Foscarnet; Fundus Oculi; Ganciclovir; Humans; Opportunistic Infections; Phosphonoacetic Acid; Retinitis; Vision Disorders

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adrenal Cortex Hormones; Capsaicin; Carbamazepine; Demyelinating Diseases; Ganciclovir; HIV-1; HTLV-I Infections; Humans; Muscular Diseases; Neuritis; Neuromuscular Diseases; Peripheral Nervous System Diseases; Polyneuropathies; Zidovudine

Herpes viruses (HSV, CMV, VZ) are very frequent in AIDS patients and often exist in a chronic or progressive form. Clinically evident CMV retinitis occurs in approximately 10 per cent of AIDS patients but can be effectively treated with a new nucleoside analogue DHPG (Gancyclovir). Perianal ulcers, proctitis, and other clinical syndromes caused by HSV can be effectively treated with acyclovir (ACV) and HSV recurrences can be prevented by daily administration of ACV. Zoster in a young adult may be the first indication of immunodeficiency due to HIV. Because VZV is less susceptible to ACV than HSV, intravenous ACV or high-dose oral therapy is required to achieve inhibitory blood levels.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Cytomegalovirus; Ganciclovir; Herpesviridae Infections; Herpesvirus 3, Human; Humans; Opportunistic Infections; Simplexvirus

Acyclovir (Zovirax) and zidovudine (Retrovir) dominate antiviral therapy. They interfere with the multiplication of herpes viruses (acyclovir) and HIV (zidovudine) by incorporation into nascent DNA chains and interruption of the further linking of nucleotides. All types of infection caused by herpes simplex virus are potentially treatable by acyclovir, but treatment has to start to be effective. It is especially important to treat immunosuppressed patients because their infections are more prolonged and severe. A typical attack of herpes zoster in an immunocompetent patient is shortened by about 2 days if high doses of acyclovir are given within 3 days of the start of the skin lesions, but unfortunately the incidence of post-herpetic neuralgia is not diminished. Zidovudine lowers early mortality in patients with AIDS and pneumocystis carinii pneumonia. However, much of the effectiveness of zidovudine is lost later; the average prolongation of life in treated patients is estimated to be about 1 year. Some two thirds of patients with AIDS can be treated with zidovudine; in the others the drug is ineffective (Kaposi's sarcoma) or contraindicated. Frequent blood counts are necessary to monitor myelotoxicity.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Herpesviridae Infections; Humans; Virus Replication; Zidovudine

Cytomegalovirus, herpes simplex, and herpes zoster are responsible for the majority of cases of viral retinitis. Herpes zoster also has been strongly incriminated as a causal agent in acute retinal necrosis. Effective chemotherapy exists for retinitis caused by herpes simplex and herpes zoster, along with acute retinal necrosis. Conventional antiviral therapy and immunomodulators are ineffective in the treatment of cytomegalovirus retinitis in patients with acquired immune deficiency disorder. Ganciclovir, a new antiviral agent, has significantly reduced visual morbidity in these patients. Recurrence of the infection is not uncommon while patients are on the drug or when the agent is discontinued, because ganciclovir is virostatic and does not stop viral replication in the retina. The inability to control this viral retinitis using presently available chemotherapy indicates a need to examine other therapeutic modalities.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Cytomegalovirus Infections; Ganciclovir; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Humans; Retinitis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Foscarnet; Ganciclovir; Humans; Immunologic Deficiency Syndromes; Organophosphorus Compounds; Phosphonoacetic Acid

Potent effective antiviral drugs recently have been licensed for several viral diseases, ushering in a new era in the treatment of viral diseases. Several unique features in the process of a viral infection have been identified as target points for inhibition. The unique steps and the interfering compounds are the subject of this review.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Amantadine; Antiviral Agents; Ganciclovir; Humans; Ribavirin; Vidarabine; Virus Diseases

ACV is an effective agent for the treatment and prophylaxis of HSV infections in both IC and immunologically normal individuals. The drug is well tolerated in both populations and is not significantly associated with clinical or laboratory toxicities. Because of the great potential benefit and low risk, organ transplant recipients and patients with hematologic malignancies undergoing induction chemotherapy should be screened routinely for HSV antibodies; seropositive individuals should receive prophylactic ACV during the period of most profound immunosuppression. Immunologically normal individuals with frequently recurring genital HSV or serious complications associated with outbreaks are candidates for long-term suppression with ACV.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Drug Resistance, Microbial; Herpes Simplex; Humans; Immune Tolerance

New therapies and diseases causing immunosuppression have provoked new and devastating ocular diseases. The possible reasons for the vulnerability of the retina to opportunistic infections are discussed. The clinical patterns of disease caused by common opportunistic agents are described, and current treatment available is reviewed.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Candidiasis; Chorioretinitis; Cytomegalovirus Infections; Eye Diseases; Herpes Simplex; Herpes Zoster; Humans; Immunity, Cellular; Immunosuppression Therapy; Infant, Newborn; Retina; Retinal Diseases; Retinal Vessels

We studied 39 AIDS patients from 1989 to 1996, with previous history of herpes zoster. Twelve of them received acyclovir (ACV) secondary prophylaxis. There were 31 males and 8 females, mean age 33.9 years (19-60) during first herpes zoster. Transmission was sexual in 71.8%. Among these 39 patients, 78 herpes zoster episodes occurred. Median CD4 lymphocytes was 18/mm3 (0-232) among the 12 patients with ACV prophylaxis. Mean posology of ACV was 2,400 mg (1,600-4,000) per day, during mean 10 months (median 4 months). ACV prophylaxis was used because of high frequence of herpes zoster (more than 4) (4 cases), neurologic complications in 4 cases (1 myelitis, 1 myeloradiculitis, 1 vascularitis and 1 meningo-encephalitis), disseminated herpes zoster in 4 cases and one hyperalgic zoster. Ten from these 12 patients occurred no zoster recurrence. Among patients without prophylaxis, zoster recurrences were more frequent at 12 months (68% versus 22% among patients with prophylaxis). This prophylaxis seems to be interesting, particularly in deep immunocompromised patients (CD4 < 50/mm3) with serious herpes zoster or frequent recurrences (more than 4). However, since protease inhibitors treatments, zoster incidence is decreasing in HIV+ patients. This prophylaxis will probably be less usefull than before.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Female; Follow-Up Studies; Herpes Zoster; Humans; Male; Middle Aged; Treatment Outcome

The safety and efficacy of cidofovir gel for treatment of acyclovir-unresponsive herpes simplex virus infections in AIDS patients was evaluated in a randomized, double-blind, multicenter trial. Cidofovir (0.3% or 1%) or placebo gel was applied once daily for 5 days. Ten of 20 cidofovir-treated and none of 10 placebo-treated patients had complete healing or >50% decreased area (P = .008); 30% of cidofovir-treated patients versus 0 placebo recipients had complete healing (P = .031). Viral shedding ceased in 13 (87%) of 15 cidofovir-treated and 0 of 9 placebo-treated patients (P = .00004). For cidofovir-treated patients, median time to complete or good response was 21 days, and median time to negative viral culture was 2 days (P = .025, P = .0001, respectively). Median lesion area decreases were 58% for cidofovir-treated versus 0 for placebo-treated patients (P = .005), and mean pain score changes were -1.84 versus -0.34 (P = .042). Application site reactions occurred in 25% of cidofovir-treated and 20% of placebo-treated patients; none was dose-limiting. Cidofovir therapy provided significant benefits in lesion healing, virologic effect, and pain reduction.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Animals; Antiviral Agents; Cells, Cultured; Chlorocebus aethiops; Cidofovir; Cytosine; Double-Blind Method; Drug Resistance, Microbial; Female; Foscarnet; Gels; Herpes Simplex; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Mouth Mucosa; Organophosphonates; Organophosphorus Compounds; Simplexvirus; Vero Cells

To evaluate the association between acyclovir use and survival in patients with advanced human immunodeficiency virus infection, observational data from 1044 persons with AIDS or AIDS-related complex (ARC) and < or = 250 CD4 cells/mm3 following initiation of zidovudine were analyzed. Of these patients, 336 (32%) received regular acyclovir (> or = 6 weeks in 2 months). There were no differences in mortality data between acyclovir users and nonusers overall or when analyzed from 1 year after first use of zidovudine, from time of AIDS in those with ARC at enrollment, from patients with AIDS or < 100 CD4 cells/mm3 at enrollment, or from patients taking acyclovir for up to 10 months. Acyclovir use was associated with increased mortality (relative hazard, 1.28; P = .057) independent of herpesvirus infections and of other characteristics associated with mortality. In this study, the use of acyclovir at doses for treatment of herpes simplex virus infection in combination with zidovudine was not associated with prolonged survival.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Complex; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Prospective Studies; Survival Rate; Zidovudine

We examined the recurrence rate of herpetic uveitis (HU) in 13 patients (group A) treated prophylactically with long-term systemic acyclovir (600-800 mg/day) and compared it with that of 7 patients with no prophylactic therapy (group B). HU was diagnosed on the basis of a history of dendritic or disciform keratitis accompanied by iridocyclitis and iris atrophy. The study population consisted of 12 men and 8 women with a mean age at onset of uveitis of 52.9 years (range 19-78 years). All patients were followed for at least 8 months. The mean follow-up time of patients on long-term oral acyclovir was 26.0 months. In this group, only one patient experienced a single recurrent episode of uveitis while on 600-800 mg/day of acyclovir therapy; two additional patients had recurrence of HU within 16.2 months after the acyclovir dose was tapered below 600 mg/day. In striking contrast, 16 recurrences occurred in the 7 patients of group B (p < 0.05). Of these, the initial recurrence occurred within an average of 4.3 months following cessation of therapy. There was a significant difference (p < 0.05) in the mean recurrence-free interval between patients in group A (24.6 months) and those in group B (3.4 months). Herpetic uveitis is a serious ocular disease in which recurrence of inflammation results in severe ocular complications. The long-term use of oral acyclovir may be of benefit in the prevention of recurrences, and hence may reduce the blinding complications of this disease. Efforts at completing a randomized, placebo-controlled trial on this matter by the Herpes Epithelial Disease Study Group were unsuccessful due to insufficient patient recruitment.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Adult; Aged; Antiviral Agents; Atrophy; Female; Humans; Iridocyclitis; Iris; Keratitis, Dendritic; Keratitis, Herpetic; Male; Middle Aged; Recurrence; Treatment Outcome; Uveitis; Visual Acuity

To examine the effect of acyclovir use on disease progression and survival in human immunodeficiency virus (HIV)-seropositive persons treated with zidovudine.. Four university-based or -affiliated clinics.. Prospective cohort study of homosexual and bisexual men with semi-annual follow-up. Intent-to-treat Cox models were fit to determine the relation between the use of acyclovir (modeled as a time-dependent covariate) and disease progression, controlling for baseline and time-dependent clinical and laboratory prognostic variables. The acquired immunodeficiency syndrome (AIDS)-free duration and survival time were calculated from the first use of zidovudine. Analysis included study visits 7 to 17 (from 1987 to 1992).. 786 HIV-seropositive participants in the Multicenter AIDS Cohort Study who began zidovudine therapy before a clinical diagnosis of AIDS; of these, 515 subsequently received acyclovir. Participants were asked at each visit whether they had "used any medication for health reasons not related to AIDS or if they had taken any medication to help fight AIDS or the HIV virus"; 488 patients indicated acyclovir use under either or both questions, and 242 patients indicated only the latter use.. The use of acyclovir for any indication was not associated with an effect on progression to AIDS but was associated with a 26% decrease in the risk for death (relative hazard, 0.74; P = 0.07). The use of acyclovir for HIV infection was also not associated with an effect on progression to AIDS but was associated with a 36% decrease in the risk for death (relative hazard, 0.64; P = 0.01). To further investigate these findings, we examined dose, constancy, and timing of acyclovir use. The median daily dose of acyclovir used for HIV infection was between 600 and 800 mg. No apparent dose effect on survival was found. Longer uninterrupted use of acyclovir for any indication was associated with an 18% decrease in the risk for death for three or more consecutive visits (relative hazard, 0.82; P = 0.23), a 28% decrease for four or more consecutive visits (relative hazard, 0.72; P = 0.09), and a 7% decrease per visit based on the cumulative number of visits while the patient received acyclovir (relative hazard, 0.93 per visit increase; P = 0.03). Use of acyclovir for any indication and use of acyclovir for HIV infection were each associated with a 44% decreased probability of death if the drug was used after AIDS developed (P = 0.007 and P = 0.005, respectively) but not before. To further investigate the prolongation of survival, two landmark analyses were done. The first analysis began at a landmark of 1 year after initiation of zidovudine therapy and compared three groups of patients: those who used acyclovir at or before this landmark, those who had never started acyclovir or started the drug after the landmark, and those who had never used acyclovir. The 90% survival times were 1325, 1059, and 982 days, respectively. The second analysis began at a landmark of developing either a CD4 count less than 50 cells/microL or clinical AIDS. The 90% survival times for the three groups were 398, 261, and 176 days, respectively.. Our analysis suggests that consistent use of acyclovir at a dose sufficient to suppress herpetic recurrences (that is, 600 to 800 mg/d) has a clinically significant effect on prolonging survival in a well-characterized cohort with extensive previous exposure to herpesvirus infections. Further clinical investigation of low-dose acyclovir with concomitant antiretroviral therapy is warranted.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; HIV Infections; Humans; Male; Proportional Hazards Models; Prospective Studies; Survival Analysis; Treatment Outcome; Zidovudine

To determine the efficacy of high-dose oral acyclovir in preventing cytomegalovirus (CMV) and other herpesvirus disease in patients with advanced HIV disease and to evaluate its effect on patient survival.. Double-blind, placebo-controlled randomized trial of up to 1 year's therapy.. Outpatient clinics in 16 hospitals in Europe and Australia.. A total of 302 patients with Centers for Disease Control and Prevention stage IV HIV disease, seropositive for CMV and with CD4+ lymphocyte counts < or = 150 x 10(6)/l.. Oral acyclovir (800 mg, four times daily) or matching placebo for 48 weeks.. Time to development of CMV and other herpesvirus disease. Following the results of another study, the protocol was amended to make survival a second major endpoint.. Acyclovir failed to reduce the incidence of CMV disease: the probability of developing CMV disease at 1 year was 0.24 and 0.23 in the placebo and acyclovir groups, respectively (P = 0.53). However, acyclovir significantly reduced the probability of dying at 1 year of follow-up (from 0.39 to 0.23; P = 0.018). As expected, acyclovir significantly reduced the incidence and frequency of herpes simplex virus disease. There were no notable differences between treatment groups in clinically adverse experiences and no changes in haematological parameters to indicate clinically significant drug-induced toxicity.. High-dose acyclovir failed to reduce the incidence of CMV disease, but significantly reduced the probability of dying at 1 year of follow-up.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Adult; Antiviral Agents; Australia; Cytomegalovirus Infections; Double-Blind Method; Europe; Female; Follow-Up Studies; Herpesviridae Infections; HIV Core Protein p24; Humans; Leukocyte Count; Male; Middle Aged; Pneumonia, Pneumocystis; Proportional Hazards Models; Survival Analysis; Time Factors; Treatment Outcome

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Cohort Studies; Drug Synergism; Humans; Male; Survival Rate; Zidovudine

To evaluate the efficacy and safety of zidovudine (ZDV) at a maintenance dose of 250 mg every 6 h alone or as cotherapy with acyclovir (ACV; 800 mg every 6 h) as treatment for AIDS and AIDS-related complex (ARC).. Double-blind, randomized, placebo-controlled clinical trial of up to 1 year's therapy.. Teaching hospital ambulatory clinics in eight European countries and Australia.. A total of 131 patients with AIDS and 134 with ARC were enrolled and followed from 1986 to 1988.. Time to development of AIDS-defining opportunistic infections and AIDS-associated neoplasms, survival assessed at 1 year after entry, performance status, body weight, CD4+ cell counts.. During the study period, 46 (36%) ZDV recipients and 37 (27%) cotherapy recipients developed opportunistic infections. The probability of an ARC patient progressing to AIDS (1982 Centers for Disease Control criteria) was 0.18 and 0.15 [95% confidence interval (CI) for difference, -0.17 to 0.11] for the ZDV alone and cotherapy recipients, respectively. After excluding patients who experienced an opportunistic infection during the first 4 weeks of therapy, the probability was 0.13 and 0.099 (95% CI for difference, -0.16 to 0.10) for the ZDV and cotherapy recipients, respectively. Thirty-six patients treated with single-agent therapy [28 (41%) AIDS and eight (12%) ARC patients] and 15 cotherapy recipients [13 (21%) AIDS and two (3%) ARC patients] died during the study. There was a significant difference in time to death between the cotherapy and ZDV alone groups for both AIDS (P = 0.014) and ARC (P = 0.045) patients, with cotherapy patients surviving longer. Infections related to herpesviruses, but not cytomegalovirus, were reduced in patients receiving ACV therapy. CD4+ cell counts in both arms generally increased initially and then declined. Forty-six per cent of patients in the ZDV group (59% of AIDS and 31% of ARC patients) and 52% of patients in the cotherapy group (69% of AIDS and 34% of ARC patients) experienced bone-marrow suppression. Red cell transfusions were administered to 33% of ZDV alone recipients and 34% of cotherapy recipients.. These data show that the addition of high-dose ACV cotherapy to ZDV for patients with AIDS and advanced ARC results in a statistically significant improvement in survival with minimal increase in the risk of toxicity.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Complex; AIDS-Related Opportunistic Infections; CD4-Positive T-Lymphocytes; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Leukocyte Count; Male; Safety; Zidovudine

To evaluate changes in serum HIV p24-antigen levels in a subset of patients who participated in a European/Australian double-blind, placebo-controlled trial evaluating the efficacy of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) in patients with AIDS, AIDS-related complex (ARC) or Kaposi's sarcoma (KS).. Double-blind, placebo-controlled randomized clinical trial of less than or equal to 6 months' therapy.. Samples were obtained from patients attending teaching hospital outpatient clinics in seven European countries and Australia.. One hundred and ninety-seven HIV-infected patients (60 with AIDS and 137 with ARC or KS).. Serum HIV p24-antigen levels measured using the Abbott HIV solid-phase enzyme immunoassay.. Of 76 ARC/KS patients who were initially HIV p24-antigen-positive, one out of 25 randomized to placebo, eight out of 23 to zidovudine and 11 out of 28 to the zidovudine/acyclovir combination became antigen-negative. The proportion of patients who became antigen-negative was significantly higher in both the zidovudine group (P = 0.016) and the zidovudine/acyclovir group (P = 0.004), compared with the placebo group. There were no statistical differences between the zidovudine and the zidovudine/acyclovir groups. During the trial p24-antigen levels in the zidovudine-treated patients reached their minimum after 4-8 weeks of therapy, and tended to increase gradually thereafter. Disease progression occurred irrespective of whether p24-antigen levels declined during therapy. No association between p24-antigen responses to therapy and baseline disease stage, Karnofsky score or baseline CD4 cell count was detectable.. Acyclovir does not potentiate the effect of zidovudine on p24-antigen levels. Change in antigen level in response to antiviral therapy needs further investigation before it is used as a surrogate marker for clinical efficacy of antiviral therapy.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Complex; Double-Blind Method; Drug Therapy, Combination; HIV Core Protein p24; Humans; Zidovudine

Herpes simplex virus (HSV) resistant to acyclovir can produce persistent mucocutaneous ulcerative disease in patients with the acquired immunodeficiency syndrome (AIDS). The incidence of clinically significant acyclovir-resistant HSV disease has dramatically increased since the advent of the AIDS epidemic. The primary mechanism of acyclovir resistance is induction of viral mutants defective or deficient in thymidine kinase, the viral-encoded enzyme, which catalyzes the rate-limiting step in the triphosphorylation of acyclovir to its active form (acyclovir triphosphate). Foscarnet, a potent inhibitor of HSV DNA polymerase, does not require phosphorylation for its antiviral activity. This compound has been found to be effective in the treatment of acyclovir-resistant HSV infection by several investigators. A recently completed dose-comparative trial of foscarnet in AIDS patients with acyclovir-resistant HSV has confirmed the safety and efficacy of two doses of foscarnet (40 mg/kg every 8 or 12 hours) in the treatment of this disease, as well as providing preliminary evidence supporting the utility of foscarnet maintenance therapy in delaying recurrence of HSV lesions. Analysis of data from this trial has been complicated by the tremendous variability in lesion size at initiation of therapy, making any statistically valid comparison of treatment regimens almost impossible. A further trial in AIDS patients with acyclovir-resistant HSV infection has been designed to define better the role of foscarnet maintenance and, in light of evidence that a significant proportion of initial recurrences are due to acyclovir-sensitive HSV, to examine the potential utility of acyclovir maintenance following foscarnet induction therapy.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Drug Resistance, Microbial; Foscarnet; Herpes Simplex; Humans; Phosphonoacetic Acid

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Drug Therapy, Combination; Humans; United Kingdom; Zidovudine

Most strains of herpes simplex virus that are resistant to acyclovir are susceptible in vitro to both foscarnet and vidarabine. We conducted a randomized trial to compare foscarnet with vidarabine in 14 patients with the acquired immunodeficiency syndrome (AIDS) and mucocutaneous herpetic lesions that had been unresponsive to intravenous therapy with acyclovir for a minimum of 10 days. The patients were randomly assigned to receive either foscarnet (40 mg per kilogram of body weight intravenously every 8 hours) or vidarabine (15 mg per kilogram per day intravenously) for 10 to 42 days. In the isolates of herpes simplex virus we documented in vitro resistance to acyclovir and susceptibility to foscarnet and vidarabine.. The lesions in all eight patients assigned to foscarnet healed completely after 10 to 24 days of therapy. In contrast, vidarabine was discontinued because of failure in all six patients assigned to receive it. The time to complete healing (P = 0.01), time to 50 percent reductions in the size of the lesions (P = 0.01) and the pain score (P = 0.004), and time to the end of viral shedding (P = 0.006) were all significantly shorter in the patients assigned to foscarnet. Three patients had new neurologic abnormalities while receiving vidarabine. No patient discontinued foscarnet because of toxicity. Although initial recurrences of herpes simplex infection after the index lesion had healed tended to be susceptible to acyclovir, acyclovir-resistant infection eventually recurred in every healed patient, a median of 42.5 days (range, 14 to 191) after foscarnet was discontinued.. For the treatment of acyclovir-resistant herpes simplex infection in patients with AIDS, foscarnet has superior efficacy and less frequent serious toxicity than vidarabine. Once the treatment is stopped, however; there is a high frequency of relapse.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Drug Resistance, Microbial; Female; Foscarnet; Herpes Genitalis; Humans; Male; Phosphonoacetic Acid; Recurrence; Simplexvirus; Stomatitis, Herpetic; Vidarabine

To evaluate the efficacy and safety of high-dose intravenous acyclovir combined with oral zidovudine as suppressive therapy for cytomegalovirus retinitis in patients with AIDS, a single-arm, outpatient, open-label, phase II pilot study was performed. Between July 1989 and July 1990, 12 men with AIDS, cytomegalovirus retinitis, and salvageable vision received intravenous acyclovir, 10 mg/kg of body weight every 8 h, and oral zidovudine after successful induction therapy with intravenous ganciclovir, 5 mg/kg every 12 h for 14 days. Patients were evaluated weekly. Ten of 12 patients were followed to the time of retinitis progression; two were withdrawn from the study because of concomitant life-threatening infection. The median duration of acyclovir and zidovudine therapy before retinitis progression occurred was 32 days. None of the eight uninvolved eyes in the 10 evaluatable patients developed cytomegalovirus retinitis during study participation. These data suggest that high-dose intravenous acyclovir with zidovudine provides some benefit in suppressing cytomegalovirus retinitis.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Adult; Cytomegalovirus Infections; Drug Evaluation; Drug Therapy, Combination; Eye Infections, Viral; Follow-Up Studies; Humans; Injections, Intravenous; Male; Middle Aged; Ophthalmoscopy; Pilot Projects; Retinitis; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Anemia; Antiviral Agents; Clinical Trials as Topic; Cytomegalovirus Infections; Erythropoietin; Ganciclovir; Humans; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Cytomegalovirus Infections; Humans

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Complex; Clinical Trials as Topic; Double-Blind Method; Humans; Multicenter Studies as Topic; Opportunistic Infections; Random Allocation; Zidovudine

Both oral and intravenous acyclovir administration for seven days in the early stages of infectious mononucleosis caused an inhibition of oropharyngeal Epstein-Barr virus (EBV) replication. Minimal effect on clinical symptoms was observed. Development of normal cellular and humoral EBV-specific immunity was seen in all patients. The combination of intravenous acyclovir and prednisolone treatment for 10 days in 11 patients with fulminant mononucleosis caused transient cessation of virus shedding in all patients. A dramatic clinical effect on pharyngeal symptoms and on fever was seen in nine of 11 patients within 72 hours. Treatment with chemotherapy or irradiation is recommended in EBV-associated B cell lymphomas seen in immunosuppressed, transplanted, and human immunodeficiency virus-I seropositive patients. No effect of acyclovir has been reported, but such therapy may be considered in the early stage when EBV induces a polyclonal B cell activation. Acyclovir treatment is effective in the EBV-genome positive hairy leukoplakia in human immunodeficiency virus-seropositive patients. No effect of antiviral therapy has been reported in the X-linked lymphoproliferative syndrome. Prophylactic use of immunoglobulin or acyclovir has been suggested in susceptible children.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Burkitt Lymphoma; Clinical Trials as Topic; Female; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immune Tolerance; Infectious Mononucleosis; Lymphoproliferative Disorders; Male; Prednisolone

We report the first randomized prospective comparative study of long-term maintenance ganciclovir (9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine, BW759U, DHPG) therapy for cytomegalovirus retinitis in patients with the acquired immunodeficiency syndrome (AIDS). Eleven retinitis patients who received a 10-day course of ganciclovir induction therapy and then were randomized to receive either immediate daily ganciclovir maintenance therapy or deferred maintenance (eight deferred maintenance, three immediate maintenance) were evaluated for drug efficacy. Median time to retinitis progression was 42 days for the immediate maintenance group compared with 16 days for the deferred maintenance group, (P = 0.07). After crossing over to maintenance therapy, patients in the deferred group had a median time to retinitis progression of 58 days compared to 16 days while not on maintenance therapy (P = 0.13). Only 9% of cultures obtained while patients received maintenance therapy were positive for cytomegalovirus, vs 40% of those obtained off maintenance (P less than 0.001). We can state then that maintenance therapy with ganciclovir delays, but does not halt, progression of cytomegalovirus retinitis and suppresses, but does not eradicate, cytomegalovirus shedding in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Clinical Trials as Topic; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Middle Aged; Prospective Studies; Random Allocation; Retinitis

Ganciclovir (BW B759U, DHPG, dihydroxy propoxymethyl guanine) was injected directly into the vitreous in 14 eyes of 11 patients with severe acquired immune deficiency syndrome (AIDS)-associated cytomegalovirus (CMV) retinitis. All 11 patients either demonstrated serious myelosuppression which precluded the continuation of intravenous ganciclovir therapy (5 patients) or were experiencing progressive CMV retinitis despite therapy with maximum-tolerable dosages of intravenous ganciclovir (6 patients). Suppression of the retinitis was observed in 11 (78%) of the 14 treated eyes. Three eyes (22%) showed no improvement after the initial intravitreal injection. One rhegmatogenous retinal detachment (RD) occurred during an injection. There were no other complications, and no intraocular drug toxicity was observed. Reactivation of CMV retinitis necessitated repeated injections in 9 (64%) of the 14 eyes. The authors' experience with these 30 intravitreal injections indicates that the procedure is safe and effective both as an alternative to intravenous ganciclovir therapy in myelosuppressed patients and as a supplement to intravenous therapy in uncontrolled CMV retinitis.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Clinical Trials as Topic; Cytomegalovirus Infections; Fundus Oculi; Ganciclovir; Humans; Injections; Injections, Intravenous; Male; Ophthalmoscopy; Retinal Detachment; Retinitis; Retrospective Studies; Vitreous Body

The effect of different dosages of ganciclovir on proved cytomegalovirus chorioretinitis was tested in a randomized trial on 11 homosexual men with AIDS. The effect of 5 mg/kg/day was as good as 10 mg/kg/day. The lower dosage had less toxicity.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Chorioretinitis; Clinical Trials as Topic; Cytomegalovirus Infections; Ganciclovir; Humans; Male; Middle Aged; Random Allocation

18 men with longstanding human immunodeficiency virus (HIV) antigenaemia but no symptoms received zidovudine in low-dose regimens (250 mg 6-hourly, 500 mg 6-hourly, or 500 mg 12-hourly) with or without acyclovir. Serum HIV antigen rose in only 1 patient and declined significantly in 13 (to below cut-off values in 9). In the 1 subject from whom HIV antigen positive cerebrospinal fluid was obtained, the fluid was antigen negative after 12 weeks of treatment. Acyclovir treatment alone or in addition did not seem to influence serum antigen levels. In 7 untreated men serum antigen levels rose or remained stable during follow-up. CD4+ cell counts increased in 14/18 treated subjects and 1/7 untreated subjects. No disease progression was observed in either group. Regression of enlarged lymph nodes was seen in the zidovudine-treated subjects. Adverse reactions to the study drugs were infrequent and mild. Anaemia caused symptoms in 2, but serious leucopenia or neutropenia was not observed.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antigens, Viral; Antiviral Agents; Double-Blind Method; Drug Evaluation; Drug Therapy, Combination; HIV; Homosexuality; Humans; Male; Random Allocation; Thymidine; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Random Allocation; Zidovudine

During 1 year of continuous suppressive therapy for frequent recurrent genital herpes, about 44% of patients taking 400 mg acyclovir twice a day had no recurrences and 4% of patients taking placebo had no recurrences (i.e., fewer patients taking acyclovir had recurrences, and when they did there were fewer recurrences). Toxicity of continuous suppressive acyclovir treatment appears to be minimal, and viral resistance developing to the drug during use of suppressive therapy has not been a problem, although it does occur. Patients with acquired immunodeficiency syndrome with recurrent herpes may be given 400 mg acyclovir five times a day for 5 days or until the eruption clears and then 400 mg three times a day for 1 or 2 months followed by 400 mg twice a day thereafter. Herpes zoster of immunocompromised patients, including patients with acquired immunodeficiency syndrome, may be treated with 800 mg oral acyclovir five or six times a day for 5 to 10 days depending on the response, and they may derive additional benefit from concomitant topical acyclovir.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Drug Administration Schedule; Female; Herpes Genitalis; Herpes Zoster; Humans; Male; Recurrence

Ganciclovir is a congener of acyclovir with in vitro activity against cytomegalovirus. Ninety-seven patients with the acquired immune deficiency syndrome (AIDS) and a serious cytomegalovirus infection received ganciclovir, 3.0 to 15 mg/kg per day. Viremia cleared during drug therapy in 88 percent of patients. Viral shedding from urine and throat ceased or became inapparent during treatment in 78 percent and 68 percent of patients, respectively. Among patients with cytomegalovirus retinitis, 87 percent of evaluable patients had improvement in (30 of 60) or stabilization (22 of 60) of their disease. However, when the drug was discontinued, progression or recurrence of disease always occurred. Long-term suppressive therapy with ganciclovir, 5.0 mg/kg five to seven times weekly, prevented the recurrence of cytomegalovirus disease (p less than 0.001). The drug was eliminated by renal excretion, and in patients without renal impairment (creatinine clearance rates of more than 60 ml/minute/1.73 m2), ganciclovir has a mean half-life of 4.2 hours. Significant neutropenia and leukopenia occurred in 55 percent and 32 percent of patients, respectively.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Clinical Trials as Topic; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Kinetics; Male; Opportunistic Infections; Time Factors; Viremia

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Anti-Retroviral Agents; Antiviral Agents; Bronchial Neoplasms; Bronchoscopy; Cerebrospinal Fluid; Encephalitis, Varicella Zoster; Fatal Outcome; Herpesvirus 3, Human; Herpesvirus 8, Human; Humans; Male; Medication Adherence; Sarcoma, Kaposi; Spinal Puncture; Young Adult

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Follow-Up Studies; Herpes Simplex; HIV Infections; Humans; Simplexvirus

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Anti-Infective Agents, Local; Antiviral Agents; Foot Ulcer; Herpesvirus 1, Human; Humans; Male; Middle Aged; Treatment Outcome; Valacyclovir; Valine

To report a case of progressive outer retinal necrosis (PORN) presenting as a cherry red spot.. Case report.. A 53-year-old woman with recently diagnosed HIV and varicella-zoster virus (VZV) aseptic meningitis developed rapid sequential vision loss in both eyes over 2 months. Her exam showed a "cherry red spot" in both maculae with peripheral atrophy and pigmentary changes, consistent with PORN. Due to her late presentation and the rapid progression of her condition, she quickly developed end-stage vision loss in both eyes.. PORN should be considered within the differential diagnosis of a "cherry red spot." Immune-deficient patients with a history of herpetic infection who present with visual loss warrant prompt ophthalmological evaluation.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Antiviral Agents; Blindness; Disease Progression; Eye Infections, Viral; Female; Herpes Zoster Ophthalmicus; Humans; Middle Aged; Mucolipidoses; Retinal Necrosis Syndrome, Acute; Valacyclovir; Valine

Pseudoepitheliomatous hyperplasia (PEH) clinically and histologically mimics squamous cell carcinoma (SCC), specifically in patients with HIV and AIDS.. A 51-year-old G3P2 with AIDS and history of vulvar cancer presented with large bilateral exophytic lesions on the vulva, grossly appearing neoplastic. Initial biopsies of the lesions were interpreted as vulvar SCC. After resolution with empiric treatment with acyclovir for possible herpes simplex virus type 2 outbreak, additional slides were reviewed, and cells with viral inclusions were identified, making the final diagnosis PEH in association with herpes simplex virus type 2 infection.. Although PEH is infrequently encountered, PEH should be considered in the differential diagnosis of vulvar lesions. A multidisciplinary approach including the gynecologist, pathologist, and infectious disease specialists can optimize patient outcome.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Carcinoma, Squamous Cell; Diagnosis, Differential; Female; Herpes Genitalis; Herpesvirus 2, Human; Humans; Hyperplasia; Middle Aged; Treatment Outcome; Vulvar Neoplasms

To study the demographics, clinical features, treatment, and visual outcomes of progressive outer retinal necrosis (PORN) in a group of Thai patients.. All cases of AIDS with a clinical diagnosis of PORN in a major tertiary referral hospital in southern Thailand between January 2003 and June 2007 were retrospectively reviewed. Demographic data, clinical features, treatment regimens, and visual outcomes were analyzed.. Seven patients (11 eyes) were studied. The mean age was 44.7 years. The median CD4 count was 12 cells/mm3. A known history of cutaneous zoster was documented in 57% of cases. The median follow-up period was 17 weeks. Fifty-seven percent of the patients had bilateral disease. A majority of eyes (45.4%) had initial visual acuity of less than 20/50 to equal to or better than 20/200. About two-thirds of the eyes had anterior chamber cells. Vitritis and retinal lesions scattered throughout both posterior pole and peripheral retina were found in 72.7%. Either intravenous acyclovir in combination with intravitreal ganciclovir injections or intravenous aclyclovir alone was used for initial treatment. Retinal detachment occurred in 54.5%. Final visual acuity worsened (loss of 3 lines on the ETDRS chart or more) in 60%. Visual acuity was no light perception in 45.5% at the final recorded follow-up.. Demographics, clinical features and treatment outcomes of PORN in this group of Thai patients were comparable with studies from other countries. Visual prognosis is still poor with current treatment regimens.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Asian People; Disease Progression; Drug Therapy, Combination; Female; Follow-Up Studies; Ganciclovir; Humans; Injections, Intravenous; Male; Middle Aged; Prognosis; Retinal Detachment; Retinal Necrosis Syndrome, Acute; Retrospective Studies; Thailand; Treatment Outcome; Visual Acuity

Typical progressive outer retinal necrosis (PORN) is an acute ocular infectious disease in acquired immunodeficiency syndrome (AIDS) patients with extremely low CD4+ T-cell counts. It is a form of the Varicella- zoster virus (VZV) infection. This destructive infection has an extremely rapid course that may lead to blindness in affected eyes within days or weeks. Attempts at its treatment have had limited success. We describe the case of a bilateral PORN in an AIDS patient with an initial CD4+ T-cell count >100 cells/microL that developed after initiation of highly active antiretroviral therapy (HAART). A 29-year-old Thai female initially diagnosed with human immunodeficiency virus (HIV) in 1998, presented with bilaterally decreased visual acuity after initiating HAART two months earlier. Multiple yellowish spots appeared in the deep retina without evidence of intraocular inflammation or retinal vasculitis. Her CD4+ T-cell count was 127 cells/microL. She was diagnosed as having PORN based on clinical features and positive VZV in the aqueous humor and vitreous by polymerase chain reaction (PCR). Despite combined treatment with intravenous acyclovir and intravitreous ganciclovir, the patient's visual acuity worsened with no light-perception in either eye. This case suggests that PORN should be included in the differential diagnosis of reduced visual acuity in AIDS patients initiating HAART with higher CD4+ T-cell counts. PORN may be a manifestation of the immune reconstitution syndrome.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; Female; Ganciclovir; Herpesvirus 3, Human; Humans; Necrosis; Polymerase Chain Reaction; Retina; Retinal Diseases; Thailand

Viral syndromes can present with various cutaneous manifestations, from the morbilliform eruption of measles to the papular lesions of molluscum. The systemic manifestations of viral illness can be similarly varied, with different presentations in each individual. We describe a patient with recently diagnosed AIDS who presented to the emergency department with hemorrhagic papules and shortness of breath. She was found to be severely thrombocytopenic, and a Tzanck smear revealed multinucleate giant cells. She received a diagnosis of immune thrombocytopenic purpura (ITP) and primary varicella pneumonia. Acyclovir and intravenous immunoglobulin (IVIG) were initiated. Her respiratory status improved after 5 days of treatment and her cutaneous lesions healed, with some scarring. We believe the rapid resolution and benign outcome of this patient's varicella infection may have been attributed to the concomitant initiation of IVIG with antiviral therapy.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Chickenpox; Drug Therapy, Combination; Female; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Pneumonia, Viral; Purpura, Thrombocytopenic

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Aqueous Humor; DNA, Viral; Drug Therapy, Combination; Female; Fluorescein Angiography; Foscarnet; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Macula Lutea; Middle Aged; Polymerase Chain Reaction; Retinal Necrosis Syndrome, Acute; Tomography, Optical Coherence

Herpes simplex virus (HSV) infections are usually chronically recurrent in the normal population and represent a significant cause of morbidity in immunocompromised patients. Acyclovir (ACV) is widely used for the treatment and prophylaxis of HSV infections. The emergence of ACV-resistant strains has been frequently reported as a result of long-term ACV therapy.. Despite the widespread use of ACV, there are no data available in our area on the frequency of ACV-resistant HSVs. The purpose of this study was to evaluate the susceptibility of HSV isolated from normal subjects and patients with acquired immunodeficiency syndrome (AIDS) to ACV.. HSVs were isolated from the orofacial region of normal individuals and patients with AIDS. The susceptibility of isolated HSV strains to various concentrations of ACV was determined by plaque reduction assay. The sensitivity of the viral strains was expressed as IC(50) (the concentration of drug reducing the viral plaque by 50%).. One hundred and thirty-three isolates from 102 normal subjects and 31 patients with AIDS were tested. One HSV-1 isolate from normal individuals had intermediate susceptibility. Two ACV-resistant isolates (one HSV-1 and one HSV-2), with IC(50) > or = 2 to < or = 3 microg/mL, and one highly resistant HSV-2 isolate, with IC(50) > or = 5 microg/mL, were detected in patients with AIDS.. Our data show that the prevalence of ACV-resistant strains is very low in the general immunocompetent population; however, in patients with AIDS, the prevalence of ACV-resistant strains is remarkable (P = 0.001). Alternative antiherpetic agents should be employed to control and reduce the emergence of ACV-resistant strains in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adolescent; Adult; AIDS-Related Opportunistic Infections; Animals; Antiviral Agents; Child; Chlorocebus aethiops; Drug Resistance, Viral; Female; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Immunocompetence; Male; Microbial Sensitivity Tests; Middle Aged; Polymerase Chain Reaction; Vero Cells

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Brain; Cerebral Ventricles; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Epstein-Barr Virus Infections; Fatal Outcome; Ganciclovir; Humans; Hydrocephalus; Immunoglobulin G; Magnetic Resonance Imaging; Male; Toxoplasmosis, Cerebral

Five patients (4 males; mean age, 46.4 years) with painful verrucous perianal lesions caused by herpes simplex virus are described. All patients had had AIDS for a long time and were using highly active antiretroviral therapy. CD4+ counts ranged from 73 to 370/mm3. All lesions were submitted to resection under subdural anesthesia. Histologic examinations revealed epithelial hyperplasia and dense inflammatory process, composed mainly of lymphocytes and plasma cells, extended just to the hypodermis. Immunohistochemistry was positive for herpes simplex virus Type 2 in four patients and for herpes simplex virus Type 1 in one patient, and did not detect human papillomavirus antigens. Three patients had recurrences after 3, 10, and 12 months. Resection was performed on two patients; one had a new recurrence after three months. Oral acyclovir eliminated the lesion in the third patient. The analysis of our patients suggests that herpes simplex virus, Types 1 and 2, may cause verrucous lesions simulating neoplasia in patients with AIDS using antiretroviral therapy.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Anal Canal; Anus Neoplasms; Diagnosis, Differential; Female; Herpes Simplex; Humans; Hypertrophy; Immunohistochemistry; Inflammation; Male; Middle Aged; Recurrence

A heterogeneous herpes simplex virus type 2 (HSV-2) population was characterised from an AIDS patient with relapsing genital ulcer. The isolate had an unusual antiviral spectrum, showing resistance to penciclovir and susceptibility to acyclovir. Two viral populations were plaque purified, one resistant and the other susceptible to both antiviral drugs. The resistant clone was deficient in thymidine kinase (TK) activity and a nucleotide substitution, thymine for cytosine, at position 153 was identified in its TK gene. This mutation resulted in an amino acid change, arginine to tryptophan, in the ATP binding site. In the deficient mutant, a loss of virulence was observed in mice.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Amino Acid Substitution; Animals; Antiviral Agents; Base Sequence; Chlorocebus aethiops; DNA, Viral; Drug Resistance, Viral; Female; Genes, Viral; Guanine; Herpes Genitalis; Herpesvirus 2, Human; Humans; Male; Mice; Thymidine Kinase; Vero Cells; Virulence

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cidofovir; Cytosine; Drug Resistance, Viral; Fatal Outcome; Female; Foscarnet; Herpes Zoster; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Organophosphonates

An 8-year-old girl with acquired immunodeficiency syndrome presented with fever and alteration of consciousness. She had a history of persistent cryptococcal meningitis. She developed multiple discrete umbilicated papules that resembled cutaneous cryptococcosis on the second day of admission. Skin biopsy revealed an ulcer with a wedge-shaped necrosis of the dermis. The edge of the ulcer showed intracellular edema, margination of nucleoplasm and multinucleated cells, consistent with herpes infection. The diagnosis of varicella-zoster virus infection was confirmed by the identification of herpesvirus DNA from the lesion and differentiation from other herpesviruses by restriction fragment length polymorphism (RFLP) method. Intravenous acyclovir was given at a dose of 500 mg/m2, three times daily for 14 days which resulted in resolution of the skin lesions within 2 weeks.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Chickenpox; Child; DNA, Viral; Exanthema; Fatal Outcome; Female; Herpesvirus 3, Human; Humans; Polymorphism, Restriction Fragment Length; Skin Ulcer

We developed and evaluated methods for the analysis and interpretation of the baseline risk heterogeneity in meta-analysis of individual patient data (MIPD) based on information on predictive factors. We used data from a typical MIPD of eight clinical trials (1792 patients, 2947 years of follow-up) on the efficacy of high-dose acyclovir in human immunodeficiency virus infection. Cox models with four predictive factors (age, disease state, CD4 cell count and hemoglobin levels) were used to estimate predicted individual hazards both for single trials and for various MIPD modeling methods (simple pooling, adjusted for study, stratified per study, fixed and random effects for predictors). For each study and for each method of MIPD synthesis, we estimated the odds ratio for death in the upper versus the lower quartile of predicted risk (Extreme Quartile Odds Ratio, EQuOR) and the respective rate ratio (Extreme Quartile Rate Ratio, EQuRR). Only the CD4 cell count showed a significantly heterogeneous predictive effect across the eight studies (P =.024). The EQuOR of single studies ranged from 3.5 (little heterogeneity) to 24 (intermediate heterogeneity), substantially lower than the EQuOR of the MIPD (167 to 275, depending on the model used). The EQuRR values ranged from 3.5 to 77 for single studies and from 77 to 116 for the various MIPD models. Predictive modeling can be a major strength of MIPD, when performed and interpreted with standardized approaches. All models consistently show that MIPD may be a study design with extreme heterogeneity of patient baseline risk.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Biometry; CD4 Lymphocyte Count; Data Interpretation, Statistical; HIV Infections; Humans; Meta-Analysis as Topic; Models, Statistical; Predictive Value of Tests; Proportional Hazards Models; Randomized Controlled Trials as Topic

The features of oral hairy leukoplakia (OHL) have been widely reported in the literature. However, no studies have described this lesion in the Australian setting. This study retrospectively examines, with respect to specific clinical factors, the prevalence of OHL in a South Australian HIV-infected population.. Clinical data were collected from the records of 197 HIV-infected patients who had attended the Adelaide Dental Hospital between January 1986 and February 1995. Data were analysed using the chi-square test.. The prevalence of OHL in South Australian HIV-infected patients was 45.2 per cent. The study found the presence of OHL was not related to CD4+ T-lymphocyte count or AIDS-defining illness nor did the length of time a patient had been infected with HIV relate to the presence of OHL. An association was observed between a reduced prevalence of OHL in patients who were taking antiviral medication.. The prevalence of OHL in South Australia is comparable with results of other studies. This study supports the notion that OHL is not an indicator of immunosuppression in South Australian HIV-infected patients. Further longitudinal studies are required to ascertain the relationship of OHL to HIV disease progression.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Aged; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiviral Agents; CD4 Lymphocyte Count; Chi-Square Distribution; Female; HIV Infections; Humans; Leukoplakia, Hairy; Male; Middle Aged; Prevalence; Retrospective Studies; South Australia; Time Factors; Zidovudine

A 46-year-old man with HIV infection and AIDS presented with a large perianal ulcerated vegetative lesion that developed over a 1-year period. He had a past history of recurrent genital herpes infection, treated successfully each time with acyclovir. The perianal lesion developed while he was taking prophylactic acyclovir. Clinically, there were features suspicious of a carcinoma and a biopsy was reported as showing dysplasia. Therefore, the lesion was resected in its entirety. Histologically, there were prominent pseudo-epitheliomatous hyperplasia and chronic ulceration associated with herpesvirus infection. There was no evidence of dysplasia or malignancy. It is important to be aware of chronic vegetant herpesvirus infection, as clinical appearances are unusual and some methods of identification, such as smears or biopsy, may not be sufficient for diagnosis. Viral culture or PCR may need to be performed for a definite diagnosis to alleviate prolonged discomfort and avoid unnecessary radical surgery.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Anus Neoplasms; Carcinoma; Diagnosis, Differential; Epithelial Cells; Fissure in Ano; Herpes Simplex; Humans; Hyperplasia; Immunocompromised Host; Male; Middle Aged; Papillomaviridae

This case confirms that cutaneous herpes simplex virus (HSV) infections in many AIDS patients is important not only for the difficulty in diagnosis of herpetic lesions, but also for the possibility that co-infection by HSV and HIV can adversely affect prognosis in these patients.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Female; Fingers; Herpes Simplex; Humans; Skin Ulcer; Wound Healing

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Drug Resistance; Female; Foscarnet; Herpes Genitalis; Humans; Pregnancy; Pregnancy Complications, Infectious

We report on a 29-year-old severely compromised acquired immunodeficiency syndrome patient who developed retrobulbar optic neuritis 5 weeks after an episode of cutaneous herpes zoster infection. During the optic neuritis, varicella zoster virus could be demonstrated in the cerebrospinal fluid. The neuritis responded well to treatment with foscarnet, but, 3 weeks into therapy, varicella zoster retinitis developed. Additional treatment with intravenous acyclovir stopped progression of the retinitis and resulted in healing of the retinal lesions. This case suggests that retrobulbar optic neuritis can be regarded as a prodrome of imminent acute retinal necrosis. Early recognition and prompt therapy with combined antivirals may prevent the development of this devastating ocular complication of varicella zoster infection.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Female; Foscarnet; Herpes Zoster; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Male; Optic Neuritis; Visual Acuity

Twenty-eight patients with upper extremity infections and positive for the human immunodeficiency virus (HIV) were identified. The risk factor for HIV infection was intravenous drug injection in 24 patients, homosexual contact in 3, and heterosexual contact in 1. Eight of the patients had the acquired immunodeficiency syndrome. Two of the cases were prolonged herpetic infections of more than 6 months' duration that did not respond to oral acyclovir. The other 26 cases were bacterial in origin. Twenty-six of 28 cases responded to therapy with resolution of the infection. One patient refused surgical treatment and one died of systemic illness before resolution of the hand infection.

Topics: Abscess; Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Arm; Cause of Death; Cohort Studies; Drug Resistance, Microbial; Female; Hand; Herpes Simplex; Heterosexuality; HIV Infections; Homosexuality, Male; Humans; Male; Middle Aged; Retrospective Studies; Risk Factors; Sepsis; Soft Tissue Infections; Staphylococcal Infections; Streptococcal Infections; Substance Abuse, Intravenous

We report the case of an adult patient with acquired immune deficiency syndrome (AIDS) presenting with acute dyspnoea and cutaneous disseminated lesions suggestive of an atypical varicella. The chest radiograph and the computed tomography (CT)-scan revealed a miliary pneumonia. On a previous serum sample varicella-zoster (VZV)-specific serum immunoglobulin (Ig)G titre was 1/200. A high dose acyclovir treatment was effective, but recurrences occurred twice when the treatment was discontinued. During the first recurrence the polymerase chain reaction (PCR) detected the presence of VZV in the bronchoalveolar lavage (BAL) sample. These findings confirmed the diagnosis of secondary varicella with pulmonary involvement. Secondary varicella pneumonia has not been reported in a human immunodeficiency virus (HIV)-infected adult until now. The use of PCR on a BAL sample was very useful in this case because viral culture remained negative. Recurrences of the varicella pneumonia suggested that a maintenance treatment was required in this deeply immunocompromised patient.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Bronchoalveolar Lavage Fluid; Chickenpox; Herpesvirus 3, Human; Humans; Male; Pneumonia, Viral; Polymerase Chain Reaction; Recurrence

To characterize further a chronic epithelial keratitis caused by varicella-zoster virus infection in patients with acquired immunodeficiency syndrome (AIDS).. Patients with AIDS and chronic epithelial keratitis associated with varicella-zoster virus from 3 institutions were identified. Patient records were reviewed retrospectively for the following data: medical and demographic characteristics, techniques of diagnosis, physical findings, course, response to treatment, and outcome.. Sixteen patients were studied. CD4+ T-lymphocyte cell counts were available in 11 patients, with a median of 0.034 x 10(9)/L (range, 0-0.094 x 10(9)/L). Two patients had no history of a zosteriform rash. In the remaining patients, the interval between rash and keratitis ranged from 0 days to 6 years. In all cases, the keratitis was chronic and characterized by gray, elevated, dendriform epithelial lesions that stained variably with fluorescein and rose bengal. The peripheral and midperipheral cornea was most commonly affected, and, in 13 of the 16 patients, the lesions crossed the limbus. Pain was a prominent feature, occurring in 12 of 16 patients. In 9 of 12 patients tested, varicella-zoster virus was identified by culture, direct fluorescent antibody testing, polymerase chain reaction testing, or a combination of these studies, with direct fluorescent antibody testing (6 of 8 positive results) and polymerase chain reaction testing (3 of 3 positive results) appearing to be the most sensitive. Response to antiviral medication was variable.. In patients with AIDS, varicella-zoster virus may cause a chronic infection of the corneal epithelium. The keratitis is characterized by dendriform lesions, prolonged course, and frequently by extreme pain. It can occur without an associated dermatitis.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Aged; Antiviral Agents; Arabinofuranosyluracil; CD4 Lymphocyte Count; Chronic Disease; Epithelium, Corneal; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Keratitis, Dendritic; Male; Middle Aged; Retrospective Studies

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Anti-HIV Agents; Child, Preschool; Cidofovir; Cytosine; Drug Resistance, Microbial; Facial Dermatoses; Foscarnet; Herpes Simplex; Humans; Male; Organophosphonates; Organophosphorus Compounds; Treatment Failure

Varicella zoster virus retinitis (VZVR) in patients with AIDS, also called progressive outer retinal necrosis (PORN), is a necrotising viral retinitis which has resulted in blindness in most patients. The purposes of this study were to investigate the clinical course and visual outcome, and to determine if the choice of a systemic antiviral therapy affected the final visual outcome in patients with VZVR and AIDS.. A review of the clinical records of 20 patients with VZVR from six centres was performed. Analysis of the clinical characteristics at presentation was performed. Kruskall-Wallis non-parametric one way analysis of variance (KWAOV) of the final visual acuities of patients treated with acyclovir, ganciclovir, foscarnet, or a combination of foscarnet and ganciclovir was carried out.. Median follow up was 6 months (range 1.3-26 months). On presentation, 14 of 20 patients (70%) had bilateral disease, and 75% (15 of 20 patients) had previous or concurrent extraocular manifestations of VZV infection. Median initial and final visual acuities were 20/40 and hand movements, respectively. Of 39 eyes involved, 19 eyes (49%) were no light perception at last follow up; 27 eyes (69%) developed rhegmatogenous retinal detachments. Patients treated with combination ganciclovir and foscarnet therapy or ganciclovir alone had significantly better final visual acuity than those treated with either acyclovir or foscarnet (KWAOV: p = 0.0051).. This study represents the second largest series, the longest follow up, and the first analysis of visual outcomes based on medical therapy for AIDS patients with VZVR. Aggressive medical treatment with appropriate systemic antivirals may improve long term visual outcome in patients with VZVR. Acyclovir appears to be relatively ineffective in treating this disease.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Analysis of Variance; Antiviral Agents; Eye Infections, Viral; Female; Foscarnet; Ganciclovir; Herpes Zoster; Herpesvirus 3, Human; Humans; Male; Middle Aged; Retinal Detachment; Retinitis; Retrospective Studies; Treatment Outcome; Visual Acuity

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Female; Fingers; Hand Dermatoses; Herpes Simplex; Humans

Patients with herpes lesions who do not respond to acyclovir are eligible for expanded access to topical cidofovir gel. Cidofovir is active against many viruses and is currently approved for use via injection to treat CMV retinitis in persons with AIDS (available under the name Vistide, or cidofovir for injection). To be eligible, patients must have mucocutaneous herpes simplex infection unresponsive to at least a 10-day course of treatment with acyclovir. For more information call Gilead Sciences Medical Information.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cidofovir; Cytosine; Drug Approval; Gels; Herpes Simplex; Humans; Organophosphonates; Organophosphorus Compounds

To determine the efficacy of recombinant interferon alpha in the treatment of progressive multifocal leukoencephalopathy associated with the acquired immunodeficiency syndrome (AIDS).. Open label, uncontrolled study.. Neurological unit and clinical AIDS program, Boston City Hospital, Boston, MA.. Four consecutive AIDS patients with pathologically confirmed progressive multifocal leukoencephalopathy.. Each patient received alpha interferon for 4-12 weeks in a dose of 5-10 million units daily, administered subcutaneously. In addition, two of the four were taking acyclovir 2400 mg/day orally over the same period.. None of the patients showed any clinical response to the therapy; the mean survival was 14 weeks. No adverse effects of the treatment were encountered.. Despite anecdotal evidence that alpha interferon is effective in the treatment of progressive multifocal leukoencephalo pathy in non-AIDS patients, the experience of these patients suggests that the drug is of no benefit in AIDS-related PML.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Opportunistic Infections; Humans; Interferon-alpha; Leukoencephalopathy, Progressive Multifocal

A man with acquired immunodeficiency syndrome developed a generalized rash and bilateral dendritic epithelial keratitis without retinitis. Cytologic examination of superficial corneal scrapings showed many megalosyncytial giant cells that were highly characteristic of cytomegalovirus (CMV) infection. Viral cultures yielded CMV from 2 separate specimens obtained by corneal epithelial debridement from both eyes. The slightly elevated, opaque, branching, nonulcerative epitheliopathy recurred after corneal scrapings and persisted despite oral and topical antiviral therapy. Stromal keratouveitis subsequently developed. This case report confirms that CMV can produce corneal involvement and suggests that CMV keratitis may be an emergent complication of acquired immunodeficiency syndrome.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Anti-Inflammatory Agents; Antigens, Viral; Antiviral Agents; Cornea; Corneal Stroma; Cytomegalovirus; Cytomegalovirus Infections; Epithelium; Eye Infections, Viral; Fibroblasts; Fluorometholone; Humans; Keratitis; Lung; Male

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Anti-Infective Agents; Antiviral Agents; Ceftazidime; Cephalosporins; Granulocyte Colony-Stimulating Factor; Humans; Male; Neutropenia; Pyrimethamine; Sulfadiazine; Trimethoprim, Sulfamethoxazole Drug Combination

Herpes simplex virus (HSV) strain 1737, acyclovir-resistant and uniformly thymidine kinase-deficient (tkD) by all conventional assays, clinically reactivated in an AIDS patient in the absence of antiviral drug pressure. Investigation of its neurovirulence and latency characteristics in a mouse model using a tkD plaque isolate (1737-14), however, yielded a neurovirulent, homogeneous, acyclovir-sensitive, tk wild type (tkWT) strain (1737-14ME), while trigeminal ganglia from a surviving animal yielded a heterogeneous tkD/tkWT population (1737-14/10(5)B). Heterogeneity may have arisen due to selection of a preexisting tkWT subpopulation or to genetic reversion. "Ultralow" levels of tk, undetectable by conventional means, may be sufficient for reactivation while retaining the acyclovir-resistant phenotype. A possible mechanism for spontaneous reactivation of 1737 is in vivo complementation between heterogeneous tk populations. Eradication of acyclovir-resistant, tkD virus does not ensure subsequent reactivations to be acyclovir-sensitive, and alternating antivirals may be required for effective therapy.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Animals; Drug Resistance, Microbial; Female; Herpesvirus 2, Human; Humans; Mice; Mice, Inbred BALB C; Middle Aged; Mutagenesis; Precipitin Tests; Thymidine Kinase; Viral Plaque Assay; Virus Activation; Virus Latency

Herpetic esophagitis (HE) associated with human immunodeficiency virus (HIV) is a rare condition mainly reported as isolated cases. We thus decided to study this association and analyze the possible predisposing factors, clinical and endoscopic presentations, and clinical response to treatment. Thirty-four HIV-1-infected patients were identified: 27 had histologically or virologically confirmed HE and seven had probable HE, a retrospective diagnosis based on the efficacy of acyclovir given alone. The median CD4 cell count was 15/mm3. Recent predisposing factors (such as nasogastric procedures, steroid therapy, and anticancer therapy) were noted with regard to 16 of the 34 patients (47%). Odynophagia and/or chest pain occurred in 30 patients (88%). At the time of diagnosis of HE, extraesophageal herpes was found in only 13 patients (38%). Superficial ulcers of the distal third of the esophagus were present in 17 (50%). Among 20 of the 27 patients with confirmed HE that could be evaluated, therapy with acyclovir led to complete resolution in 16 and partial response in 3; 1 patient died of HE. Five patients (15%) suffered confirmed or possible relapses. The mean interval between the diagnosis of HE and death was 8.8 months. Herpes simplex virus may be responsible for ulcerated esophagitis that occurs in the advanced stages of AIDS and that can be safely treated with acyclovir before a definitive diagnosis is made.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adrenal Cortex Hormones; Adult; Aged; AIDS-Related Opportunistic Infections; Antineoplastic Agents; CD4 Lymphocyte Count; Esophagitis; Esophagoscopy; Female; Herpes Simplex; Humans; Intubation, Gastrointestinal; Male; Middle Aged; Recurrence; Retrospective Studies; Risk Factors; Treatment Outcome

This report describes two patients with acquired immunodeficiency syndrome (AIDS) and herpes zoster myelopathy. Patient one had a T-8 myelitis that preceded the onset of T-8-distribution zoster and was followed by cervical myelopathy. Antibody to varicella zoster virus (VZV) was present in the CSF. He never received steroids or other immunosuppressive drugs, and his condition improved dramatically after treatment with intravenous acyclovir. The second patient had a rapidly progressive myelitis with paralysis of both legs. Detection of VZV DNA and antibody to VZV in his CSF led to successful treatment with famciclovir despite discontinuation of dexamethasone and earlier treatment failure with acyclovir. These cases support the idea that VZV myelopathy in the immunosuppressed host is caused by virus invasion. CSF analysis for antiviral antibody and for VZV DNA by polymerase chain reaction are helpful in establishing the diagnosis. Aggressive antiviral therapy is advised.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; DNA, Viral; Herpes Zoster; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myelitis

The purpose of this study was to describe the clinical characteristics and course of peripheral ulcerative keratitis (PUK) secondary to herpes varicella-zoster virus in patients with the acquired immunodeficiency syndrome (AIDS). Three AIDS patients with ocular herpes zoster infection (mean age at onset, 33.0 years; range, 30-42) developed PUK. The three patients had skin involvement, and two of them had bilateral keratouveitis. All were treated with high-dose oral acyclovir (4 g/day) with or without topical antiviral therapy. Two of the patients responded well to oral acyclovir, but one of them stopped the treatment, and bilateral progressive outer retinal necrosis and lethal encephalitis developed. The third patient had a recurrent episode of inflammation with PUK, extensive stromal scarring, and deep neovascularization. AIDS patients with herpes varicella-zoster virus infection may have severe and protracted corneal manifestations, including PUK. The correct diagnosis and aggressive early long-term systemic antiviral treatment must be instituted to control inflammation, ulcer progression, and complications.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Adult; Anti-Inflammatory Agents; Antiviral Agents; Corneal Ulcer; Herpes Zoster Ophthalmicus; Humans; Male; Ophthalmic Solutions; Prednisolone; Recurrence; Skin Diseases, Viral; Uveitis

Progressive outer retinal necrosis is a destructive retinopathy found in patients with acquired immune deficiency syndrome. Treatment of this disorder has been unsuccessful in reported patient series, with the patients experiencing profound bilateral loss of vision.. We treated six patients with combination antiviral therapy, usually with intravenous foscarnet and either ganciclovir or acyclovir.. These six patients retained a visual acuity of 20/100 or better in at least one eye for the remainder of their lives (a period > 4 months for each patient). Retinal detachments developed in four patients, for which vitrectomy and silicone oil tamponade were required.. A combination of intravenous antiviral therapy and aggressive vitrectomy techniques to repair any associated detachments may allow the preservation of useful visual acuity in patients with progressive outer retinal necrosis. This is the first reported series of successful long-term treatment of patients with this disorder.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Female; Foscarnet; Fundus Oculi; Ganciclovir; Herpes Zoster; Herpes Zoster Ophthalmicus; Humans; Infusions, Intravenous; Male; Retinal Detachment; Retinal Necrosis Syndrome, Acute; Silicone Oils; Visual Acuity; Vitrectomy

In persons with AIDS (PWAs), cytomegalovirus (CMV) infection can cause a broad spectrum of clinical manifestations. The most common clinical manifestations associated with CMV infection in PWAs and the most current approaches to treatment and prevention of CMV disease are reviewed. Manifestations discussed include those involving ocular disease, and diseases of the gastrointestinal and central nervous systems. Prophylactic treatment for CMV disease includes the use of oral ganciclovir and valaciclovir. Concluding comments address the development of antiviral resistance by CMV. Tables include listings of potential strategies for use of oral ganciclovir prophylaxis in PWAs, and mechanisms by which CMV strains become resistant to ganciclovir, foscarnet, and cidofovir.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Central Nervous System Diseases; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Digestive System Diseases; Foscarnet; Ganciclovir; Humans; Valacyclovir; Valine

Retinal infections caused by the varicella-zoster virus (VZV) have been reported in immunocompetent and immunocompromised individuals. Two cases of a VZV-related retinitis are described with the characteristic features of the recently described progressive outer retinal necrosis (PORN) syndrome. Both patients suffered from the acquired immunodeficiency syndrome (AIDS) with greatly reduced peripheral blood CD4+ T lymphocyte counts, and presented with macular retinitis without vitritis. The disease was bilateral in one case and unilateral in the other. The clinical course was rapidly progressive with widespread retinal involvement and the development of rhegmatogenous retinal detachment with complete loss of vision in the affected eyes despite intensive intravenous antiviral therapy. VZV DNA was identified in vitreous biopsies, by molecular techniques based on the polymerase chain reaction (PCR), in both patients. At present, the use of very high-dose intravenous acyclovir may be the best therapeutic option in these patients for whom the visual prognosis is poor. Intravitreal antiviral drugs could also contribute to the management of these cases.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; DNA, Viral; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Male; Necrosis; Polymerase Chain Reaction; Prognosis; Retina; Retinal Detachment; Retinitis; Vitreous Body

A Caucasian homosexual man with AIDS and cytomegalovirus retinitis presented with facial pain and episodic confusion, had several seizures and became obtunded. An electroencephalogram was suggestive of herpes simplex encephalitis. The diagnosis was confirmed by detection of herpes simplex virus type 2 (HSV 2), but not type 1, DNA in cell-free cerebrospinal fluid (CSF) after amplification by nested polymerase chain reaction. The patient also had evidence of concomitant cytomegalovirus (CMV) infection with detectable CMV DNA in CSF. With high-dose acyclovir the patient recovered. Analysis of a follow up CSF sample taken four months later showed no detectable HSV-2 DNA.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Cytomegalovirus Infections; DNA, Viral; Encephalitis, Viral; Herpes Simplex; Humans; Male; Middle Aged; Polymerase Chain Reaction

Certain drugs bind to anionic phospholipids of lysosomal membranes and produce progressive intracellular accumulation of lamellar inclusions. We studied two patients treated for opportunistic infections associated with the acquired immunodeficiency syndrome (AIDS), who developed bilateral ocular surface changes suggestive of drug-induced corneal lipidosis.. Two patients with AIDS had translucent vacuoles within the corneal epithelium and mild conjunctival hyperemia. Because the differential diagnosis included microsporidial keratoconjunctivitis, biopsies of the ocular surface were performed for histopathologic analysis.. Transmission electron microscopy of corneal epithelial debridement and conjunctival biopsy specimens showed intracellular, electron-dense lipoidal bodies and multilaminated lysosomal inclusions suggestive of a drug-induced lipidosis. Both patients also had tubuloreticular inclusions in conjunctival capillary endothelial cells. The ocular surface changes resolved within one to three months after dosage reduction or discontinuation of systemic ganciclovir and acyclovir.. Drug-induced phospholipidosis is a cause of punctate corneal epitheliopathy during AIDS, but the responsible agent remains to be identified.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Biopsy; Cornea; Corneal Diseases; Ganciclovir; Humans; Lipidoses; Male

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Opportunistic Infections; Female; Foscarnet; Ganciclovir; Herpesviridae Infections; Humans; Male; Retrospective Studies; Risk Factors; Sarcoma, Kaposi

We describe a fatal case of varicella-zoster virus myelitis that was preceded by neurological symptoms for 10 months in a patient with human immunodeficiency virus infection and an extremely low CD4 cell count (20/microL). The patient was also receiving chronic acylovir therapy for suppression of herpes complex. Despite chronic unilateral periauricular and facial pain, which was later accompanied by upper- and lower-extremity weakness, a cutaneous eruption never developed. It is hypothesized that a blunted inflammatory response in the spinal cord--possibly related to a very low CD4 cell count--and long-term acylovir administration might have contributed to the atypical manifestation might have contributed to the atypical manifestation of varicella-zoster virus-related neurological disease in this immunocompromised patient.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Chronic Disease; Fatal Outcome; Herpes Zoster; Herpesvirus 3, Human; Humans; Male; Myelitis, Transverse

The purpose of this study was to determine the frequency of HSV infections and recurrences among HIV-infected patients and to examine different regimens for suppression of HSV recurrence. A randomized retrospective chart review of HIV-infected patients at a public hospital in Los Angeles County was conducted. We reviewed 224 patients' charts; 26 percent had AIDS based on the 1987 CDC definition. HSV infection was documented as a clinical event in 51 records (23 percent). Patients with an AIDS diagnosis had a greater incidence (53 percent) of HSV infections than did those with a diagnosis of symptomatic or asymptomatic HIV infection (p < 0.001, Fisher's exact test). Recurrences of HSV occurred in 26 (51 percent) of the 51 HSV-infected persons during a period of 1042 patient months. Eighteen patients who had received acyclovir suppression at 600 mg/day had three HSV recurrences in 382 patient months, whereas 14 who received 400 mg/day had eight recurrences in 282 patient months (p = 0.02). HSV infections occur in 23 percent of HIV-infected patients, increasing to 53 percent in AIDS patients. Acyclovir suppression prevents recurrent HSV, and a dosage of 600 mg/day is more effective than 400 mg/day.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Decision Making; Female; Herpes Simplex; HIV Infections; Humans; Male; Middle Aged; Random Allocation; Recurrence; Retrospective Studies; Risk Factors; United States

Some clinical studies are indicating that acyclovir, combined with AZT, improves survival time for HIV-infected people, although exactly how acyclovir prolongs survival is not known. One study reveals a 26 percent decrease in the risk of death in persons taking both acyclovir and AZT. If acyclovir treatment was initiated after a clinical diagnosis of AIDS, the risk of death was reduced by 44 percent. These risk reductions are roughly equivalent to an increased survival time of six months to one year. Some researchers hypothesize that herpes viruses may be co-factors in the progression of HIV disease and that acyclovir suppresses herpes infections. A new clinical trial comparing low- and high-doses of a similar compound, valacyclovir, may shed light on this hypothesis.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; CD4 Lymphocyte Count; Clinical Trials as Topic; Drug Therapy, Combination; HIV Infections; Humans; Retrospective Studies; Survival Analysis; Zidovudine

Two reports submitted at the Second National Conference on Human Retroviruses reignited the controversy surrounding acyclovir's potential effect on survival in HIV-infected persons. One study found no differences in survival between those using acyclovir and those not using the drug, however, it is argued that the study did not take into account duration and continuity of acyclovir use, nor did it consider that acyclovir users were likely to have had lower CD4 counts than the nonusers. The second study involved acyclovir in combination with AZT, which also revealed no survival benefit. Large numbers of subjects withdrew, making results difficult to interpret. Also, the exclusion of people needing chronic acyclovir for suppression of frequent herpes outbreaks may have removed exactly the group in whom acyclovir would most likely extend survival. To resolve the issue, there is a need for large-scale trials with sufficient statistical power and a particular subpopulation of people with HIV who might gain the most benefit from acyclovir. Two observational studies, one utilizing the CPCRA's 5,000-person database, and the other looking at the 6,000 patients enrolled in the Adult Spectrum of Disease cohort based in Atlanta, are continuing to investigate the relationship between acyclovir and survival.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Clinical Trials as Topic; Cohort Studies; Follow-Up Studies; Humans; Multicenter Studies as Topic; Survival Analysis

In a two-part interview with AIDS Treatment News (ATN), Margaret Poscher, M.D., discusses treatment strategies, including her use of combination antiretrovirals and managed care. When asked what to do for individuals who have never been on treatment but have had a sudden dramatic drop in CD4, Dr. Poscher suggests trying the triple combination AZT plus 3TC plus ddI, as long as the viral load is very high. Unfortunately, 3TC is difficult to obtain for individuals with a CD4 count that is not below 100. Dr. Poscher shares the concerns of many others that patients under managed care are less likely to receive the care they need. If insurance does not cover certain tests or therapies, the patient is forced to pay out-of-pocket, which is often not possible. Dr. Poscher is also concerned that many patients are not receiving the aggressive combination treatments now available. Many patients are either on AZT monotherapy or ddc monotherapy, which she considers useless. She sites paperwork and time as major obstacles for physicians who are not getting involved in the 3TC expanded-access program and combination therapies. Dr. Poscher foresees an increase in treatment options, which will hopefully increase survival.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; CD4 Lymphocyte Count; Didanosine; Drug Approval; Drug Combinations; Drug Therapy, Combination; Health Services Accessibility; Humans; Insurance, Health; Lamivudine; Managed Care Programs; United States; Zalcitabine; Zidovudine

The Durable Medical Equipment Regional Carriers has recommended excluding ganciclovir, acyclovir, and vancomycin from the list of Medicare-covered drugs. Only drugs infused by a pump, as indicated in the drug's product labeling, will be covered. IV ganciclovir is not covered, even though it is the drug of choice for treating cytomegalovirus retinitis. IV acyclovir, a standard therapy for disseminated herpes simplex infection among people with AIDS, is also not covered.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Cytomegalovirus Retinitis; Foscarnet; Ganciclovir; Humans; Infusions, Intravenous; Insurance, Pharmaceutical Services; Medicare; Neoplasms; Vancomycin

The prevalence of mucocutaneous herpetic infection is especially high in patients with the acquired immunodeficiency syndrome (AIDS). In these patients, 8 p. 100 of the chronic or recurrent herpetic lesions are due to a mutant strain.. A case of very large (900 cm2) genital chronic herpetic infection is reported in a patient with AIDS (stade C3-CDC/WHO 1993). It was characterised by an acyclovir resistant strain which emerged after several anterior treatment with acyclovir. A treatment with foscarnet was administered and clinical improvement was observed as early as the fourth day, with complete reepithelialization 50 days later.. We discussed essentially the pathogenicity of the herpetic infections due to mutant strains in immunocompromised patients and on the therapeutic modalities. At the present time, foscarnet is the treatment of choice for acyclovir-resistant mucocutaneous herpes simplex.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Buttocks; Chronic Disease; Drug Resistance; Foscarnet; Herpesviridae Infections; Humans; Male; Skin Diseases, Viral

The naturally occurring polyphenolic biopolymer SP-303 has in vitro activity against both HSV-1 and HSV-2, including strains that are resistant to acyclovir. Nine AIDS patients with acyclovir-unresponsive mucocutaneous herpes simplex virus infection were treated with thrice daily topical SP-303T ointment in an open-label pilot study. Although a transient decrease in lesion size was observed in 4 patients during study drug therapy, and 3 patients sustained a quantitative decrease in virus burden, neither complete healing nor cessation of virus shedding occurred in any patient. Seven patients complained of pain or burning upon application of the study ointment, causing 1 patient to terminate the study. In summary, application of SP-303T ointment effected no significant improvement in the clinical course of 9 AIDS patients with acyclovir-unresponsive HSV infection.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Topical; Adult; Aged; Biopolymers; Catechin; Drug Resistance, Microbial; Herpes Simplex; Humans; Male; Middle Aged

The syndrome of inappropriate secretion of antidiuretic hormone is a common consequence of neurologic and pulmonary infections as well as drug intake and many other clinical situations. Its association with herpes varicella-zoster virus infections is scarcely reported in the literature. It generally appears in immunosuppressed patients suffering from serious underlying diseases. There are also a few cases of syndrome of inappropriate secretion of antidiuretic hormone related to vidarabine use. We report the case of a man infected by human immunodeficiency virus who developed a disseminated herpes varicella-zoster virus infection and symptoms due to hyponatremia caused by antidiuretic hormone excess. The patient was cured with saline hypertonic infusion, water restriction, and intravenous administration of acyclovir. To the best of our knowledge, this is the first case of this association in a human immunodeficiency virus infected patient. We propose the use of acyclovir instead of vidarabine in the management of these situations.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Herpes Zoster; HIV-1; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Syndrome

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Child, Preschool; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Infectious Disease Transmission, Vertical; Skin Diseases, Viral

We report four cases of varicella-zoster virus (VZV)-associated myelopathy in adults. Myelopathy was remitting-exacerbating in two remarkable instances, once acute and once chronic. VZV myelopathy was diagnosed based on the close temporal relationship between rash and onset of myelopathy, and for the first time, by polymerase chain reaction, which revealed VZV DNA in the cerebral spinal fluid of three patients with pleocytosis weeks to months later. Magnetic resonance imaging was abnormal in three of four patients. Although all four patients were treated at some time with intravenous acyclovir, concomitant treatment with steroids and the presence of acquired immunodeficiency syndrome in one patient prevented conclusions about a favorable response to therapy. Myelopathy after VZV infection may be remitting-exacerbating in addition to acute or chronic. Detection of VZV DNA in cerebral spinal fluid months after rash was useful for diagnosis and suggests a role for virus in the pathogenesis of myelopathy.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cerebrospinal Fluid; DNA, Viral; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myelitis; Polymerase Chain Reaction

Varicella zoster virus (VZV) is recognized as one of the major viral pathogens reactivated in patients with the acquired immune deficiency syndrome (AIDS). We report the case of meningoradiculoneuritis in an AIDS patient,associated with the isolation in the cerebrospinal fluid (CSF) of a thymidine kinase (TK)-deficient, acyclovir (ACV)-resistant strain of VZV. Although the virus was sensitive in vitro to phosphonoformate (PFA), the patient did not improve during PFA therapy and finally died. Several VZV strains isolated from this patient (including two isolates from the patient's CSF) were analyzed for their TK activity and subsequently the viral TK gene was sequenced showing a major deletion leading to a truncated protein. Their susceptibility to several antiviral agents including ACV, PFA, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU), 9-beta-D-arabinofuranosyladenine (vidarabine), (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (HPMPC), and (S)-9-(3-hydroxy-2-phosphonyl-methoxypropyl)adenine (HPMPA) was evaluated. All the virus strains isolated from this patient remained sensitive to HPMPA and HPMPC, pointing to the potential usefulness of these acyclic nucleoside phosphonates for the treatment of ACV-resistant VZV infections in immunocompromised patients.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Amino Acid Sequence; Base Sequence; Drug Resistance; Female; Herpes Zoster; Humans; Meningitis; Molecular Sequence Data; Neuritis; Radiculopathy; Thymidine Kinase

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Female; Ganciclovir; Humans; Necrosis; Retinal Diseases

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Hepatitis, Viral, Human; Herpes Simplex; Humans; Male

The spectrum of presentation of complications in patients with human immunodeficiency virus (HIV) disease is changing, in line with their improved survival. Infection of the colon with cytomegalovirus (CMV) is now more commonly encountered in clinical practice. We have reviewed the medical records of eleven patients with clinical and pathological evidence of CMV colitis. The clinical presentation, endoscopic and histological findings, and simultaneous infection of other organs with CMV are discussed. Diarrhoea in association with abdominal pain is the most frequent symptom complex in these patients and should raise the clinical index of suspicion for CMV colitis.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Colitis; Colon; Cytomegalovirus Infections; Diarrhea; Ganciclovir; Humans; Intestinal Mucosa; Male; Middle Aged; Rectum

A case of atypical varicella zoster in a 33-year-old AIDS patient is reported. The patient had had two attacks of herpes zoster within a year and was given high-dose acyclovir several times. Thereafter he developed small keratotic pellucid papules on fingers, wrists and face, which were found to contain varicella-zoster antigen by the ELISA test. Skin biopsy showed acanthosis and lack of vesication, as is usually seen in herpes infections. The atypical varicella-like lesions persisted despite repeated doses of acyclovir but cleared temporarily when the patient was given foscarnet. We believe that the prolonged therapy may have allowed selection of acyclovir-resistant varicella-zoster strains, resulting in the atypical clinical course.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Biopsy; Herpes Zoster; Humans; Male; Skin; Skin Diseases, Viral; Treatment Failure

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antibodies, Viral; CD4-CD8 Ratio; Chickenpox; Child; Female; Fundus Oculi; Herpesvirus 3, Human; Humans; Immunoglobulin G; Retinal Necrosis Syndrome, Acute; Visual Acuity

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Drug Resistance, Microbial; Herpesviridae Infections; Herpesvirus 3, Human; Humans; Meninges; Microbial Sensitivity Tests; Polyradiculoneuropathy

Infection with herpes simplex viruses (HSVs) resistant to treatment with acyclovir (9-[(2-hydroxyethoxy)-methyl]guanine, Zovirax) is a growing clinical problem in patients with AIDS and other immunosuppressed states. Most virus isolates resistant to acyclovir are deficient or defective in virally coded thymidine kinase (TK), which converts acyclovir to acyclovir monophosphate in virus-infected cells. To restore acyclovir efficacy, we synthesized acyclovir diphosphate dimyristoylglycerol, an analog of a naturally occurring phospholipid, CDP-diacylglycerol. Its biological activity was tested in WI38 human lung fibroblasts infected with the acyclovir-resistant DM21 strain of HSV, which is TK negative due to an 816-base-pair deletion in the TK coding region. Acyclovir diphosphate dimyristoylglycerol has substantial activity in DM21-infected cells (IC50 = 0.25 microM), whereas acyclovir and acyclovir monophosphate were ineffective (IC50 > 100 microM). Similar results were obtained in TK-altered and TK-deficient strains of HSV-1 and in acyclovir-resistant isolates of HSV-2 obtained from two AIDS patients. The phospholipid prodrug is active by means of TK-independent metabolic pathways that liberate acyclovir monophosphate inside the host cell. Acyclovir phosphates were 56 times greater in WI38 human lung fibroblasts incubated for 24 hr with [8-3H]acyclovir diphosphate dimyristoylglycerol relative to acyclovir. Acyclovir monophosphate added to the culture medium (outside the cell) did not circumvent the acyclovir resistance of the TK-negative DM21 mutant, presumably due to its conversion to acyclovir by phosphatases. Acyclovir diphosphate diacylglycerol prodrugs may be useful in treating TK-deficient mutant and wild-type strains of HSV.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cell Line; Defective Viruses; Drug Resistance, Microbial; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Lung; Male; Microbial Sensitivity Tests; Molecular Structure; Phosphatidylglycerols; Prodrugs; Thymidine Kinase; Virus Replication

Patients with AIDS often experience recurrent infections with varicella-zoster virus (VZV) requiring repeated or prolonged treatment with acyclovir (ACV), which may lead to the development of ACV resistance. The ACV resistance of isolates recovered from such patients is associated with diminished VZV thymidine kinase (TK) function. We determined the nucleotide sequences of the TK genes of 12 ACV-resistant VZV strains purified from nine patients with AIDS. Five VZV strains contained nucleotide deletions in their TK genes, introducing a premature termination codon which is expected to result in the production of a truncated protein. No detectable full-length TK protein could be immunoprecipitated from extracts of cells infected with these virus strains. These TK-deficient strains were cross resistant to the TK-dependent antiviral agents ACV, 9-(4-hydroxy-3-hydroxymethylbutyl-yl)guanine (penciclovir), and 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl) uracil (BVaraU). The remaining seven strains each contained a nucleotide change that resulted in an amino acid substitution in the TK protein. These substitutions occurred throughout the TK protein, namely, in the ATP-binding site, the nucleoside-binding site, between the two binding sites, and at the carboxy terminus of the protein. We determined the effects of these mutations on the stability of TK protein expression in virus-infected cells and on the sensitivity of mutants to the TK-dependent antiviral agents ACV, BVaraU, and penciclovir.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Opportunistic Infections; Amino Acid Sequence; Antiviral Agents; Arabinofuranosyluracil; Base Sequence; Drug Resistance, Microbial; Genes, Viral; Genetic Variation; Guanine; Herpesviridae Infections; Herpesvirus 3, Human; Humans; Molecular Sequence Data; Mutagenesis; Precipitin Tests; Sequence Analysis; Sequence Homology, Amino Acid; Thymidine Kinase; Viral Plaque Assay

A pilot study was initiated to explore a sequential combination antiretroviral regimen in 21 patients with AIDS or advanced human immunodeficiency virus (HIV) infection, who had received little or no prior anti-HIV therapy. The mean entry CD4 cell count was 184/mm3. Patients received 3-week cycles consisting of zidovudine plus acyclovir, dideoxyinosine, and dideoxycytidine for 1 week each. Overall, the regimen was well tolerated for up to 3 years. The principal toxicities were anemia, nausea, and vomiting; 1 patient developed retinal lesions. The mean CD4 cell count reached a peak of 64 cells/mm3 above baseline at week 8 (P = .005 compared to baseline) and remained above baseline for > 40 weeks. Patients also gained weight and had decreases in serum HIV p24 antigen. Eight patients developed opportunistic infections or tumors. Only 4 patients died during 3 years of follow-up. This regimen appears to be generally tolerable and to have anti-HIV activity. Additional studies will be needed, however, to learn how to best combine the available agents in patients with HIV infection.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Complex; Antigens, CD; Biomarkers; Body Weight; CD4 Antigens; Didanosine; Drug Administration Schedule; Drug Therapy, Combination; HIV Core Protein p24; Humans; Male; Middle Aged; Pilot Projects; T-Lymphocyte Subsets; Time Factors; Zalcitabine; Zidovudine

Severe neurotoxicity and acute renal failure developed in a patient with newly diagnosed AIDS while receiving high-dosage intravenous acyclovir for disseminated herpes zoster. Hemodialysis resulted in a rapid resolution of neurologic symptoms and was associated with a reduction in plasma acyclovir concentration. Acute hemodialysis therapy should be considered in cases of serious neurotoxicity secondary to acyclovir, especially when accompanied by renal failure.

Topics: Acquired Immunodeficiency Syndrome; Acute Kidney Injury; Acyclovir; Humans; Male; Middle Aged; Nervous System Diseases; Neurotoxins; Renal Dialysis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Arthritis; Humans; Male

A 65-year-old woman with the acquired immunodeficiency syndrome (AIDS) complicated by recurrent mucocutaneous herpes simplex virus (HSV) infection developed angioedema on the initiation of her second course of oral acyclovir therapy. Oral rechallenge in hospital three days later confirmed acyclovir hypersensitivity. Vidarabine and foscarnet therapies were abandoned after treatment failure and unacceptable toxicity. Acyclovir desensitization was accomplished using a protocol derived from oral penicillin desensitization regimens. Mucocutaneous HSV infection responded to intravenous acyclovir followed by chronic oral suppression without recurrences of HSV or hypersensitivity. This report is an example of acyclovir hypersensitivity and successful oral desensitization.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Aged; Desensitization, Immunologic; Drug Hypersensitivity; Female; Herpes Simplex; Humans; Skin Diseases, Infectious

In order to determine the sensitivity of herpes simplex virus (HSV) isolates from immunocompromised patients treated with antiviral compounds, a retrospective study was carried out in the Clinical Virology Department of the University Medical Centre, Amsterdam. Virus isolates from four AIDS patients and one bone marrow transplant recipient were examined for their sensitivity for the antiviral compounds used by means of plaque reduction assay. In some of the virus isolates, from patients in whom resistance was assumed on clinical grounds, in vitro resistance of the HSV to acyclovir (ACV) could be demonstrated, both after oral and after parenteral administration. There was a clear correlation between the clinical course of the HSV infection and in vitro resistance. ACV resistant virus isolates were sensitive to foscarnet, both clinically and in vitro. In immunocompromised patients treated for some time with ACV for HSV infection, resistance should be considered at lack of results or progression of the lesion and when necessary be demonstrated in vitro. Alternative therapy then consists of intravenous foscarnet treatment.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Bone Transplantation; Drug Resistance, Microbial; Female; Foscarnet; Herpes Simplex; Humans; Male; Phosphonoacetic Acid; Retrospective Studies; Simplexvirus

Three AIDS patients with severe cutaneous herpes simplex virus (HSV) infection refractory to therapy with acyclovir and foscarnet (2 patients) were treated with a topical preparation of trifluorothymidine (TFT) and interferon-alpha. Complete healing of lesions occurred in 1 patient; a second had significant regression of the infected area. In the third, the lesion was stabilized twice after application of the preparation and reduced in size after a subsequent treatment. In vitro studies confirmed that isolates from these patients were acyclovir- or acyclovir/foscarnet-resistant. In addition, they revealed strong synergy between TFT and interferon-alpha for these isolates and for strains with wild-type drug sensitivity profiles. Topical TFT/interferon-alpha may be of benefit in the therapy of mucocutaneous HSV infections, especially when they are resistant to treatment with systemic antiviral agents.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Combined Modality Therapy; Cytopathogenic Effect, Viral; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Female; Foscarnet; Herpes Simplex; Humans; Interferon Type I; Male; Phosphonoacetic Acid; Recombinant Proteins; Recurrence; Simplexvirus; Trifluridine; Virus Replication

A 38-year-old bisexual man with acquired immunodeficiency syndrome (AIDS) who was being treated with oral acyclovir for herpetic stomatitis had a history of blurred vision OS that was diagnosed as cytomegalovirus retinitis. The patient refused ganciclovir administration. Two additional lesions developed OS in the succeeding four months. All clinical evidence of active retinitis cleared after zidovudine was administered, and the patient has remained free of any clinically active retinal lesions for 28 months while continuing to receive acyclovir and zidovudine. Although ganciclovir and foscarnet are the drugs of choice to treat cytomegalovirus retinitis, this observation may be fortuitous for patients whose other AIDS manifestations suggest using zidovudine rather than ganciclovir or for patients whose cytomegalovirus retinitis appears to be resistant to agents currently used to treat this infection.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cytomegalovirus Infections; Eye Infections, Viral; Fluorescein Angiography; Follow-Up Studies; Fundus Oculi; HIV Seropositivity; Humans; Male; Retinitis; Visual Acuity; Zidovudine

A number of HSV-2 isolates, sequentially recovered from ulcerative ano-genital lesions of an AIDS patient during a prolonged treatment with acyclovir (ACV), have been studied at the molecular level. All of them were highly resistant to ACV (ACV-r) and shown to be virtually deficient in thymidine kinase (TK) activity. The ACV-r phenotype was demonstrated to be due to the production of truncated TK polypeptide. Structural alteration of this gene, as shown in one isolate, was caused by a chain-terminating mutation that originated from a cytidine deletion at position 520 of the TK open reading frame. This mutation generated a TGA stop codon 27 nucleotides downstream. An additional isolate was also recovered following ACV discontinuation and after a cycle of treatment with foscarnet. This isolate had lost the ACV-r trait and was characterized by a wild type TK sequence and by the production of a functional enzyme. Data presented confirm that a prolonged treatment with acyclovir can easily select ACV-r HSV-2 isolates carrying a TK- phenotype caused by a frameshift mutation. Although recovered from lesions tributary of different myelomers, these isolates may belong to the same strain that has undergone multiple cycles of reactivation and has possibly mutated during its axonal route to the skin.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Base Sequence; DNA, Viral; Drug Resistance, Microbial; Genes, Viral; Herpes Genitalis; Humans; Male; Molecular Sequence Data; Mutation; Opportunistic Infections; Simplexvirus; Thymidine Kinase

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Anus Diseases; Drug Resistance, Microbial; Herpes Genitalis; Humans; Male; Trifluridine

Hyperkeratotic lesions caused by varicella-zoster, herpes simplex, or cytomegalovirus occur in patients infected with human immunodeficiency virus type 1 (HIV-1). We have also observed this type of lesion with molluscum contagiosum.. These cases were studied to determine whether there are any pathologic changes unique to these lesions.. The cases were studied by routine microscopic examination and immunohistochemistry.. Each case showed changes diagnostic of the viral infection, which was confirmed by immunohistochemical stains for herpes simplex and cytomegalovirus. In the dermis there were fewer inflammatory cells than expected, but there was an increase in factor XIIIa-positive dendritic cells.. Varicella-zoster, herpes simplex virus, cytomegalovirus, and molluscum contagiosum can cause verrucous lesions in HIV-1-infected patients. These lesions may be related to an increase in factor XIIIa-positive dendritic cells.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cytomegalovirus Infections; Dendritic Cells; Herpes Simplex; HIV-1; Humans; Interleukins; Keratinocytes; Male; Skin Diseases, Viral; Transglutaminases; Tumor Necrosis Factor-alpha; Warts

The aim of this study was to determine the prevalence and type of symptomatic anal and perianal diseases in patients belonging to group IV of the Centers for Disease Control classification of infections with human immuno-deficiency virus. Among the 190 prospectively included patients, 31 (16.3 percent) (30 men, 29 homosexuals or bisexuals; 1 woman) had anal symptoms and were referred for proctological examination. Thirty-five "specific" diagnoses were reached in 25 (13.2 percent) patients: 21 ulcerations, 7 condyloma acuminata, 6 perianal sepsis and 1 non-Hodgkin malignant lymphoma. The causes of ulcerations were 16 herpes, one syphilitic chancre and one fissure-in-ano. Three ulcerations remained unexplained despite bacteriological, viral, and histological investigations. Eight patients underwent 10 surgical procedures without significantly delayed wound healing.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Anus Diseases; Anus Neoplasms; Condylomata Acuminata; Female; Herpes Simplex; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Opportunistic Infections; Prevalence; Prospective Studies; Ulcer

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Topical; Adult; Anti-Inflammatory Agents; Humans; Hydrocortisone; Levamisole; Male; Middle Aged; Mouthwashes; Nystatin; Pentamidine; Stomatitis, Aphthous; Tetracycline; Triamcinolone; Zidovudine

To determine whether foscarnet has potential efficacy in the treatment of acyclovir-resistant mucocutaneous varicella-zoster infection in patients with the acquired immunodeficiency syndrome (AIDS).. Open-label study.. Three university medical centers.. Five patients with AIDS who were infected with thymidine-kinase-deficient or -altered strains of varicella-zoster virus.. Foscarnet, 40 mg/kg body weight every 8 hours in 1-hour infusions for 10 or more days.. Four patients had healing in response to foscarnet therapy, and each of four tested patients became culture negative for virus during foscarnet therapy. Results of fluorescent antigen testing remained positive during therapy in two patients; one of these patients had concomitant clinical failure but the other patient healed fully. One patient had complete healing despite the emergence of resistance to foscarnet in serial specimens obtained during foscarnet therapy.. Foscarnet is a potentially effective and tolerable antiviral agent for patients with acyclovir-resistant, varicella-zoster virus infection; however, the optimal dosage and duration of therapy require further study, as does the relation between clinical findings and in-vitro susceptibility results.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cohort Studies; Drug Resistance, Microbial; Foscarnet; Herpes Zoster; Herpesvirus 3, Human; Humans; Middle Aged; Phosphonoacetic Acid; Skin Diseases, Infectious

We studied the natural history of herpes simplex virus (HSV) infection and its association with specific serum antibody in a sample of 68 HIV-infected patients with a first episode of Pneumocystis carinii pneumonia at San Francisco General Hospital in 1986. Seroprevalence was 66 and 77% for HSV-1 and HSV-2 antibody, respectively, by immunoblot assay. Twenty-seven patients had 45 HSV outbreaks diagnosed during 739 patient-months of follow-up. Median frequency of recurrence resulting in a medical visit was once every 6.5 months, and median duration of treated outbreak was 10 days. Fourteen of 48 evaluable patients seropositive for HSV-2 had no outbreak of HSV during a median follow-up of 7.5 months. Our data suggests that neither frequency nor severity of HSV were substantially increased in this group of patients, despite severe immunosuppression caused by HIV. However, validation of these results by a prospective study is required.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antibodies, Viral; Female; Herpes Simplex; HIV Infections; HIV-1; HIV-2; Humans; Immunoblotting; Male; Pneumonia, Pneumocystis; Prevalence; Recurrence; Simplexvirus

Three acyclovir resistant strains of HSV-2 were isolated from mucoulcerative lesions in a patient suffering from AIDS in whom the oral and intravenous acyclovir treatment was unsuccessful. All the isolates were classified by monoclonal antibodies and showed no differences in DNA restriction patterns.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Adult; Animals; Drug Resistance, Microbial; Herpes Genitalis; Humans; Injections, Intravenous; Male; Simplexvirus; Vero Cells

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS Vaccines; Anti-Bacterial Agents; Antiviral Agents; Clinical Trials as Topic; HIV Infections; Humans; Randomized Controlled Trials as Topic; Zidovudine

In an AIDS patient who had repeated successful treatment with acyclovir in his history, erosive herpes perianalis with herpes proctitis appeared, which persisted over several weeks. High-dose intravenous administration on of acyclovir (500-750 mg, 3 x daily, over 7 weeks) did not reveal any beneficial effects: However, almost complete clearing of the lesions occurred within 3 weeks of intravenous administration of Foscarnet (50 mg/kg body wt., 3 x daily). No relapse was seen in a follow-up period of 4 months. HSV type II was isolated by culture from the erosive lesions before treatment, but no virus was found 1 week after application of Foscarnet. The unusual chronic refractory course of a severe HSV type II infection in AIDS suggests the presence of an acyclovir-resistant HSV strain in this case. This is the first observation indicating acyclovir-resistance in the Federal Republic of Germany and a warning against the unlimited use of acyclovir in AIDS patients. Foscarnet may be beneficial in some of these cases.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Foscarnet; Herpes Genitalis; Humans; Infusions, Intravenous; Male; Opportunistic Infections; Phosphonoacetic Acid; Proctitis

The case of a 25-year-old homosexual man with large inguinal and perianal ulcers is reported. He had been pretreated extensively with acyclovir. Herpes simplex virus (HSV) was identified in the ulcer tissue by in-situ hybridization. No clinical improvement with acyclovir but a prompt response to foscarnet was noted. In a relapse after 11 weeks an acyclovir-resistant HSV type 2 was isolated. Again, a prompt response to foscarnet was noted. The case is presented in detail, and the clinical impact of resistance of HSV to acyclovir is discussed.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Anus Diseases; Drug Resistance, Microbial; Foscarnet; Herpes Simplex; Humans; Male; Phosphonoacetic Acid

The biological characterization of a number of sequential herpes simplex virus type 2 (HSV-2) isolates obtained from an AIDS patient undergoing sequential courses of antiviral treatment due to an extended mucocutaneous genital lesion is reported. Resistance to acyclovir (ACV) and related compounds was linked to a thymidine kinase-deficient (TK-) phenotype. After ACV discontinuation and a course of treatment with foscarnet, a new isolate was recovered, characterized by loss of the ACV-resistant trait and production of a functional TK enzyme. Data presented stress the need for monitoring chemosensitivity of HSV isolates in AIDS patients while suggesting that for better control of the infection, these patients should benefit from alternative treatments with drugs aimed at different viral targets.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Drug Resistance, Microbial; Follow-Up Studies; Foscarnet; Herpes Simplex; HIV-2; Humans; Male; Microbial Sensitivity Tests; Phosphonoacetic Acid

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Drug Resistance, Microbial; Foscarnet; Herpes Simplex; Humans; Injections, Intravenous; Phosphonoacetic Acid; Recurrence; Vidarabine

The isolation and description of acyclovir-resistant (ACVR) herpes simplex-2 viruses from patients with AIDS has recently been reported. These ACVR viruses were all markedly decreased in their thymidine kinase (TK) activity, and 6 of 10 of these TK viruses were able to establish latency. In addition, one of these isolates, ACVR-86012 was neuropathogenic in a murine encephalitis model. In this paper, the characteristics of these isolates with respect to TK polypeptide synthesis are examined. All but one isolate synthesized a detectable TK protein by immunoprecipitation, and 9/10 of the TK proteins had an altered electrophoretic mobility as compared to wild-type. The TK polypeptide from the neuropathogenic isolate ACVR-86012 was full-length and the gene was sequenced. An amino acid change from a glutamine to a proline at amino acid residue 105 was detected compared to the wild-type HSV-333 strain. These results indicate that an amino acid change in the NH2 portion of the TK protein is associated with a full-length peptide with decreased enzyme activity but the virus retains neuropathic virulence.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Drug Resistance, Microbial; Genes, Viral; Humans; Simplexvirus; Thymidine Kinase; Viral Plaque Assay; Viral Structural Proteins

To determine the spectrum of esophageal disease responsible for dysphagia/odynophagia in AIDS patients not responding to current oral antifungals, we studied 49 consecutive patients whose esophageal symptoms failed to improve after a minimum of 3 wk of therapy with oral ketoconazole or fluconazole. An esophageal candidiasis resistant to oral antifungals was the most frequent disease found (22 single infections and four mixed with viruses). Viral esophagitis was identified in 13 cases (eight herpes simplex virus and five cytomegalovirus), and an esophagitis of unknown origin was documented in two patients. Other causes of symptoms included peptic esophagitis (four cases), esophageal stenosis (two cases), and Kaposi's sarcoma of the esophagus (one patient). Most patients with esophageal opportunistic infection experienced prompt relief of symptoms and complete endoscopic resolution on the specific antifungal (amphotericin B or fluconazole iv) or antiviral (acyclovir or gancyclovir iv) therapy, with the exception of those with concomitant fungal and viral infection who responded poorly to treatment. We conclude that most AIDS patients with dysphagia/odynophagia who do not respond to oral antifungals have an opportunistic infection of the esophagus. Nevertheless, specific antifungal or antiviral therapy is worthwhile, because it will eradicate, at least temporarily, the causative pathogens in most such patients.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Adult; Amphotericin B; Antifungal Agents; Drug Resistance, Microbial; Esophagitis; Female; Fluconazole; Ganciclovir; Humans; Infusions, Intravenous; Ketoconazole; Male; Opportunistic Infections; Prospective Studies; Treatment Outcome

Topics: Acquired Immunodeficiency Syndrome; Adenine; Animals; Antiviral Agents; Guanine; Herpesviridae; HIV; Humans; Mice; Microbial Sensitivity Tests

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Ear Diseases; Ear, External; Facial Paralysis; Herpes Zoster; Humans; Male; Nafcillin

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Herpes Zoster; Humans; Male; Sacrococcygeal Region; Spinal Cord Diseases; Urinary Retention

A case is reported of relapsing fatal meningoencephalitis caused by a neurovirulent thymidine kinase-positive (TK+) type 2 herpes simplex virus (HSV) that developed thymidine kinase deficiency (TK-) during intravenous acyclovir therapy. A patient with AIDS was admitted for acyclovir treatment of a persistent perirectal herpetic ulcer. He subsequently developed meningoencephalitis. A TK+ type 2 HSV was isolated from a brain biopsy specimen. A progressive and fatal relapse occurred, and a TK- type 2 HSV was isolated from his cerebrospinal fluid. Restriction endonuclease analysis of viral DNA from perianal, brain, and cerebrospinal fluid isolates were similar, suggesting that they were the same viral strain. Animal virulence studies indicated significant cutaneous virulence in immunocompromised mice models for the TK- isolates. This case is notable because TK- HSV have, in the past, lacked neurovirulence and because acyclovir resistance developed during therapy and caused the patient's death.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Animals; Brain; Cerebrospinal Fluid; DNA, Viral; Drug Resistance, Microbial; Female; Herpes Simplex; Humans; Male; Meningoencephalitis; Mice; Mice, Hairless; Mice, Inbred BALB C; Mice, Nude; Restriction Mapping; Simplexvirus; Thymidine Kinase; Virulence

Mucocutaneous herpes simplex virus (HSV) infections that are resistant to therapy with acyclovir have been recognized with increasing frequency in patients with the acquired immunodeficiency syndrome, although alternative therapies in this setting have not been widely studied. Twenty-six consecutive patients are reported with human immunodeficiency virus infection, who received foscarnet therapy for acyclovir-resistant HSV. Clinical response was noted in 81% of patients; complete reepithelialization of HSV lesions occurred in 73%. Cessation of viral shedding was documented in all of the 11 patients who were recultured. Although adverse effects were frequent, in only 3 patients (12%) did toxicity necessitate discontinuation of therapy. Before foscarnet therapy, 14 patients received vidarabine for acyclovir-resistant HSV. The infection did not resolve in any of the vidarabine-treated patients, and therapy was discontinued in 4 (29%) due to toxicity.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Drug Resistance, Microbial; Female; Foscarnet; Herpes Simplex; Humans; Male; Phosphonoacetic Acid; Risk Factors; Simplexvirus; Vidarabine

A large percentage of patients in stage IV of HIV infection (CDC classification) show changes in the ocular fundus. Most frequent are functionally unimportant cotton-wool spots resulting from a HIV-associated microvasculopathy. Infectious retinitis due to opportunistic organisms is in most cases caused by cytomegalovirus (CMV). Untreated patients may become blind. In case of general or local treatment of cytomegalovirus retinitis with ganciclovir, sight may be preserved on a long-term basis. The ophthalmoscopic appearance of the typical changes and their histological substrate are presented, and modes of treatment are discussed. By direct ophthalmoscopy and visual acuity testing any physician can diagnose these fundus changes. Cotton-wool spots only require follow-up. In retinitis an ophthalmologist should be consulted. A screening procedure is suggested.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Chorioretinitis; Cytomegalovirus Infections; Eye Diseases; Humans; Opportunistic Infections; Retinal Diseases; Retinitis

We described the development of prolonged disseminated cutaneous herpes zoster in two patients with acquired immunodeficiency syndrome. Both patients developed hyperkeratotic, verrucous lesions that progressed despite acyclovir therapy. The biopsy specimens were typical of herpes infection. The development of acyclovir-resistant varicella-zoster virus during therapy was suspected clinically in the first patient and documented in vitro in the second patient. The inability to mount an effective cell-mediated immune response contributed to the prolonged course of cutaneous zoster in our patients. The hyperkeratotic nature of the skin lesions may reflect their chronic nature. Treatment with inadequate doses of acyclovir, allowing viral persistence and the selection of resistant strains of virus, may also be implicated. We recommend prolonged high-dose intravenous acyclovir therapy in the initial management of herpes zoster in patients with acquired immunodeficiency syndrome.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Adult; Chronic Disease; Drug Resistance, Microbial; Herpes Zoster; Herpesvirus 3, Human; Humans; Injections, Intravenous; Male; Recurrence; Skin Diseases, Infectious

We demonstrate for the first time the appearance of acyclovir resistance in serial varicella zoster isolates from a patient treated with acyclovir. We recovered varicella zoster virus three times over a period of 5 months from the skin lesions of this patient with AIDS who was treated with three courses of intravenous acyclovir and prolonged low-dose oral acyclovir. The isolate recovered from a typical zoster lesion before acyclovir, and one obtained from a hyperkeratotic lesion 2 months later, after intravenous and oral acyclovir, were sensitive to acyclovir and produced normal amounts of thymidine kinase. In contrast, virus recovered from lesions 5 months after the onset, when the patient had received repeated courses of acyclovir, was acyclovir-resistant and thymidine-kinase-deficient. Resistance to acyclovir was associated with persistence of lesions which failed to improve with intravenous acyclovir, but was not associated with new lesion formation.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Drug Resistance, Microbial; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Thymidine Kinase

Acyclovir (ACV)-resistant herpes simplex virus type 2 (HSV-2) was isolated from a patient with acquired immunodeficiency syndrome after long-term but intermittent ACV therapy. These thymidine kinase-defective isolates were sensitive in vitro to foscarnet. While combined therapy with ACV and interferon produced only partial clinical improvement, the in vitro effect of this combination against an ACV-resistant isolate from the patient was strongly synergistic. A short course (10-12 days) of intravenous foscarnet controlled severe ulceration, and clinical improvement lasted 6 months. After recurrence and further courses of foscarnet, however, the patient responded poorly, and subsequent HSV isolates were resistant to both ACV and foscarnet and hypersensitive to aphidicolin.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Aphidicolin; Deoxyguanosine; Diterpenes; Drug Resistance, Microbial; Female; Foscarnet; Herpes Simplex; Humans; Phosphonoacetic Acid; Simplexvirus

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Drug Therapy, Combination; HIV-1; Humans; Leukocyte Count; Male; Nephritis; Zidovudine

Four patients with human immunodeficiency virus (HIV) infection who received chronic oral acyclovir therapy for suppression of recurrent varicella zoster or herpes simplex virus infection developed persistent disseminated hyperkeratotic papules that failed to heal with intravenous or high-dose oral acyclovir therapy. Varicella zoster virus, resistant to acyclovir in vitro, was isolated from skin lesions of all four patients. Three patients were adults in whom the acquired immunodeficiency syndrome (AIDS) had been diagnosed 12 to 20 months before isolation of acyclovir-resistant varicella zoster virus. The fourth patient was a perinatally HIV-infected child who developed primary varicella infection at age 7 years when profoundly immunosuppressed (absolute CD4+ lymphocyte count less than 50 cells/microL). Mean antiviral susceptibilities (ED50 values) of the four clinical isolates compared with the ED50 values of the reference strain Oka were 85 compared with 3.3 mumol/L for acyclovir, 1.4 compared with 0.8 mumol/L for vidarabine, and 123 compared with 117 mumol/L for foscarnet. When assayed by [125I]-dC plaque autoradiography, 90% to 100% of the viral isolate populations had altered or no measurable thymidine kinase function. Acyclovir-resistant varicella zoster virus infection may complicate long-term oral acyclovir administration in patients with AIDS and may be associated with the appearance of atypical hyperkeratotic papules.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Chickenpox; Child; Drug Resistance, Microbial; Herpes Zoster; Humans; Keratosis; Male; Recurrence; Skin Diseases, Infectious

A 43-year-old homosexual man was hospitalized in April 1988 because of acute epigastric pain. It was known that he had had a HIV infection for a year, and in April 1988 it was defined as stage Walter Reed I. Acute, exudative, nonspecific pancreatitis was diagnosed. Three weeks later cerebral symptoms (disturbances of consciousness), hypoacusis, and impaired vision developed. The ocular fundus displayed areas of edema and whitish clouding in the retina, first in the left eye and later also in the right. These were initially assumed to be anemic infarctions until the differential diagnosis of acute retinal necrosis with possible herpesvirus infection was made. On the basis of ophthalmoscopic findings cytomegalovirus retinitis appeared improbable. Serologic examinations showed increased levels of IgG antibody titers of cytomegalovirus and herpes simplex virus (both 1:20,000). Therapy with intravenous infusions of Acyclovir was instituted (1500 mg/d). After a few days the patient regained consciousness as well as his hearing and vision. There was complete resolution of the retinal exudates. This excellent therapeutic result of Acyclovir therapy confirmed the diagnosis of acute retinal necrosis syndrome, identified the cerebral symptoms as herpes encephalitis, and explained the entire disease process as the first opportunistic infection in HIV infection, i.e., by that time the patient had developed stage Walter Reed 6 (AIDS). Problems of differential diagnosis and the therapeutic schedule with Acyclovir are discussed.

Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Acyclovir; Adult; Encephalitis; Herpes Simplex; Humans; Male; Ophthalmoscopy; Pancreatitis; Referral and Consultation; Retinal Necrosis Syndrome, Acute

Eighteen asymptomatic men with persistent human immunodeficiency virus type I (HIV-I) p24 antigenaemia were treated with zidovudine 250-500 mg (+/- acyclovir 800 mg) 6-hourly for 4-12 weeks, and subsequently with zidovudine 500 mg (+/- acyclovir 1600 mg) 12-hourly for 36 weeks. After 24 weeks six additional HIV antigenaemic subjects were entered and treated directly with zidovudine 500 mg 12-hourly. Over the treatment period serum HIV-I p24 (HIV-Ag) levels declined in all 24 subjects; significantly so in 17, and to below cut-off values in five. Mean serum HIV-Ag levels in different treatment groups declined in 68-78%. Initial increases in CD4+ cell counts were not sustained. Over 48 weeks serum HIV-Ag levels rose in three out of five non-treated men with persistent HIV antigenaemia, and they slightly declined in two; the mean serum HIV-Ag level in this group rose 67%. Regression of enlarged lymph nodes was seen in 19 out of 19 of the zidovudine-treated subjects. In the 24 zidovudine-treated subjects no disease progression occurred during follow-up, whereas two out of five non-treated men went on to develop CDC group IV A, and IV C-2 disease, respectively. Adverse reactions to the study drugs were infrequent and mild. Anaemia caused symptoms in two, but serious leucopenia or neutropenia was not observed. An initial positive effect on thrombocyte numbers was not sustained. These data demonstrate that in asymptomatic HIV-infected subjects zidovudine 500 mg 12-hourly is well tolerated and has a persistent inhibitory effect on viral replication.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Drug Therapy, Combination; HIV Antigens; HIV Core Protein p24; Humans; Male; Prognosis; Retroviridae Proteins; Time Factors; Zidovudine

We have treated 113 patients with zidovudine since its licensure, 80 with acquired immunodeficiency syndrome and 33 with acquired immunodeficiency syndrome-related complex. This paper reports on the efficacy and toxicity observed in these patients. Improved well-being, reduced frequency and severity of opportunist infections were notable in the first year of follow-up. More rapid improvement in pulmonary physiological tests during recovery from Pneumocystis carinii pneumonia was also observed in treated patients. Patients with lower initial platelet counts showed early increases in platelet counts. There was a consistent fall in human immunodeficiency virus (HIV) p24 antigen during treatment, although not always to undetectable levels. CD4 cell counts showed a rise in the first months of treatment but these were not sustained, despite continuing clinical benefit. Neuropsychological and clinical evidence of benefit in HIV encephalopathy are described. We have analysed the factors influencing marrow toxicity and have found that low CD4 count and the intercurrent use of ganciclovir and dapsone increase myelotoxicity. We describe the clinical and biochemical features of the myopathy associated with long-term use of zidovudine and summarise our findings on dose-reduction associated meningo-encephalitis.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Complex; Bone Marrow; Brain Diseases; Dapsone; Ganciclovir; HIV Antigens; HIV Core Protein p24; Humans; Meningoencephalitis; Muscular Diseases; Neuropsychological Tests; Opportunistic Infections; Respiratory Function Tests; Retroviridae Proteins; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; Zidovudine

To determine whether trisodium phosphonoformate (foscarnet) is efficacious in treating severe mucocutaneous disease due to acyclovir-resistant herpes simplex virus type-2 (HSV-2) infection in patients with the acquired immunodeficiency syndrome (AIDS).. Open-labeled drug administration to patients with AIDS and severe ulcerative disease due to acyclovir-resistant HSV-2 infection.. Medical floors of acute care hospital.. Four patients with AIDS who developed progressive ulcerative mucocutaneous lesions of the genitals, perineum, perianal region, or finger due to acyclovir-resistant, thymidine-kinase (TK)-negative strains of HSV-2.. Foscarnet, 60 mg/kg body weight intravenously every 8 hours (with reduced dosage for renal impairment), for 12 to 50 days.. All patients receiving foscarnet had dramatic improvement in their clinical findings with marked clearing of mucocutaneous lesions and eradication of HSV from mucosal surfaces.. Foscarnet may be an effective treatment for severe mucocutaneous disease due to acyclovir-resistant, TK-negative strains of HSV-2.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Drug Resistance, Microbial; Foscarnet; Herpes Simplex; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Organophosphorus Compounds; Phosphonoacetic Acid

We report the case of an immunocompromised patient with AIDS in whom developed a perioral and several intraoral HSV 2 lesions that persisted for more than 1 year. The virus was resistant to acyclovir but was sensitive to foscarnet. Viral isolates were thymidine kinase negative. The lesions resolved with intravenous foscarnet therapy given over a 15-week period, and when last seen, 8 months after foscarnet was discontinued, the patient had not had a recurrence.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Candidiasis, Oral; Drug Resistance, Microbial; Facial Dermatoses; Foscarnet; Herpes Simplex; Humans; Male; Organophosphorus Compounds; Phosphonoacetic Acid; Stomatitis, Herpetic

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Colitis; Cranial Nerve Diseases; Cytomegalovirus Infections; Ganciclovir; Hoarseness; Humans; Laryngeal Nerves; Male; Opportunistic Infections; Recurrent Laryngeal Nerve; Vocal Cord Paralysis

In a series of 157 patients with acquired immunodeficiency syndrome (AIDS), 46 (29%) developed cytomegalovirus (CMV) retinitis. In five patients, CMV retinitis was the initial AIDS-defining opportunistic infection (11% of patients with CMV retinitis and 3% of patients with AIDS). Retinal detachments developed in seven patients (15%) and in four were present before the institution of ganciclovir therapy. Bilateral CMV retinitis was present in 35% of patients at presentation and subsequently developed in nine (60%) of 15 patients while not being treated with ganciclovir. Conversely, none of 18 patients with unilateral disease developed bilateral disease while receiving ganciclovir. Of patients treated with ganciclovir for their CMV retinitis, 81% had a response to the drug, and 61% achieved a complete response, resulting in a nonprogressive and inactive scar. Patients who achieved a complete response with ganciclovir had a significantly longer survival than those who did not, suggesting greater immune compromise in those patients who failed to respond to ganciclovir.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adolescent; Adult; Child; Child, Preschool; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Male; Middle Aged; Retinal Detachment; Retinitis; Visual Acuity

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Drug Resistance, Microbial; Female; Ganciclovir; Humans; Immune Tolerance; Immunosuppression Therapy; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Retinitis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Animals; Drug Resistance, Microbial; Encephalitis; Herpes Simplex; Humans; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Simplexvirus; Thymidine Kinase; Virulence

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Drug Resistance, Microbial; Female; Foscarnet; Herpes Genitalis; Herpes Simplex; Humans; Organophosphorus Compounds; Phosphonoacetic Acid; Simplexvirus; Skin Diseases, Infectious

Cytomegalovirus (CMV) is an important cause of acalculous gangrenous cholecystitis in immunocompromised persons. We report a case of acalculous acute cholecystitis and active colitis associated with CMV in a patient suffering from the acquired immune deficiency syndrome. The condition was treated successfully with surgery and 9-(1,3,-dihydroxy-2-propoxymethyl)guanine intravenously.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cholecystectomy; Cholecystitis; Colitis; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Male

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Cytomegalovirus Infections; Ganciclovir; Humans; Retinitis

Disseminated cytomegalovirus (CMV) infection is a common complication of acquired immunodeficiency syndrome and contributes significantly to its morbidity and mortality. Ganciclovir, a guanosine analogue, inhibits CMV replication in vitro and in vivo, and its use can stabilize the clinical course of an affected patient. We examined the changes in body composition that occurred in four untreated patients and in eight patients who were treated with ganciclovir for serious CMV infections. Untreated patients lost weight, depleted body cell mass, as determined from total-body potassium measurements in a whole-body counter, lost body fat, as estimated from anthropometric measurements, and had a progressive fall in serum albumin concentration. In contrast, treated patients gained weight, repleted body cell mass and body fat, and increased serum albumin concentration during a three-month follow-up. In this study, it was estimated that ganciclovir therapy resulted in a net energy conservation of 2629 kJ/d. The ability to promote body cell mass repletion may be considered a demonstration of the efficacy of ganciclovir in the treatment of serious CMV infections in patients with acquired immunodeficiency syndrome.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Body Constitution; Body Weight; Cytomegalovirus Infections; Ganciclovir; Humans; Middle Aged; Nutrition Disorders; Prospective Studies; Retrospective Studies; Serum Albumin

Long-term management of cytomegalovirus (CMV) retinitis by intravitreal injection of ganciclovir was evaluated in ten patients with acquired immune deficiency syndrome (AIDS). Patients were unable to tolerate systemic ganciclovir because of severe neutropenia (8 cases), catheter-induced sepsis (1 case), or the need to continue therapy for human immunodeficiency virus (HIV) with zidovudine (ZDV) (1 case). All patients had a favorable response to initial treatment. Cytomegalovirus retinitis progressed in four fellow eyes in which treatment was deferred. Vision improved or remained stable in all but one eye. Patients were followed for a mean of 4 months and received an average of 16.6 intravitreal injections in each eye. Relapse occurred late in the course while on maintenance treatment in five eyes (33%). There was no evidence of toxicity from repeated intravitreal injections. Treatment was very well tolerated. The only severe complication in a total of 249 injections was a single case of Staphylococcus epidermidis endophthalmitis which responded to intravitreal antibiotic treatment. Intravitreal ganciclovir is an effective alternative to systemic ganciclovir in those patients with severe neutropenia and in those patients who desire to remain on systemic ZDV.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cytomegalovirus Infections; Ganciclovir; Humans; Injections; Long-Term Care; Middle Aged; Opportunistic Infections; Retinitis; Vitreous Body

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Male; Retinitis; Thrombocytopenia; Vitreous Hemorrhage

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Colony-Stimulating Factors; Cytomegalovirus Infections; Ganciclovir; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances; Humans; Retinitis

A case is reported of a 35-year-old male with established acquired immune deficiency syndrome who developed cytomegalovirus retinitis. When intravenous treatment with ganciclovir had to be withdrawn because of toxicity, one eye was treated successfully by intravitreal injections of the drug. After 15 weeks of intravitreal treatment this eye developed endophthalmitis.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Injections; Male; Retinitis; Vitreous Body

Nine patients with unilateral cytomegalovirus (CMV) retinitis were treated with intravenous infusions of the new virustatic drug DHPG (Ganciclovir). The induction dose was 10 mg/kg body weight per day (2-5 weeks). In six cases, a maintenance dose was given thereafter of 5 mg/kg body weight per day. After the induction dose, five patients had visual improvement and satisfactory cicatrization. In one patient, PVR (proliferative vitreous reaction) developed with total tractional retinal detachment. More ocular complications were seen while on longterm therapy: relapses during discontinuation because of leukopenia (three times in two patients), breakthrough (= relapse during maintenance therapy) (one case), serous retinal detachment (one case), and optic atrophy (two cases). The complications caused blindness in two further patients. Only one patient has tolerated maintenance therapy for 22 weeks without having any complications. One patient wanted to have therapy suspended and has remained free of relapse for 28 weeks while on cytostatic therapy. The eyes of two deceased patients were examined histopathologically, immunhistochemically, and ultrastructurally and the findings compared with those of an untreated case. Given at an early stage and without discontinuation, DHPG is an effective means of preventing or delaying blindness caused by cytomegalovirus retinitis in AIDS patients. The directives for an optimal dosage are subject to further prospective randomized clinical studies.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Injections; Opportunistic Infections; Retinitis; Vitreous Body

Of 147 patients with AIDS (Walter Reed 3-6), 28 showed signs of retinal infection. Toxoplasmic retinochoroiditis had developed in 5 eyes of 4 patients, whereas cytomegalovirus (CMV) retinitis occurred in 40 eyes of 24 patients. All patients with toxoplasmosis complained of visual symptoms at the first visit, but only 60% of patients with CMV retinitis had ocular symptoms at this time. The important problems involved in making a timely and correct diagnosis (early CMV retinitis vs cotton wool spots vs toxoplasmic retinitis; significance of laboratory data) are presented and discussed. The course of CMV retinitis is sometimes fast and devastating and requires immediate treatment to prevent blindness in patients who are in otherwise still fair general health. Eighteen patients (28 eyes) were treated by intravenous ganciclovir (DHPG) for 1-9 months. Initial therapy (10 mg/kg body wt., 2-4 weeks) led to regression of fundus lesions in all eyes. Under maintenance treatment (5 mg/kg BW body wt., 5 times a week), 14 eyes still demonstrated significant regression or cicatrization of the lesions, 9 eyes showed little progress and 5 eyes moderate recovery. However, 8 of 12 untreated eyes became legally blind before the patient died. None of the 23 treated eyes with useful initial visual acuity (greater than or equal to 0.2) lost visual function. Only in three cases did the drug have to be stopped because of serious side effects (severe leukopenia, pancytopenia, psychosis). Toxoplasmic retinochoroiditis healed in all affected eyes after specific treatment (pyrimethamine, sulfamethoxydiazine, clindamycin, and spiramycin in double or triple combination).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Coccidiostats; Cytomegalovirus Infections; Drug Therapy, Combination; Follow-Up Studies; Ganciclovir; Humans; Male; Middle Aged; Opportunistic Infections; Retinitis; Toxoplasmosis, Ocular

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Male

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Infusions, Intravenous; Retinitis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Retinitis

We report a case of orofacial herpes simplex virus (HSV) infection that was progressive despite multiple courses of acyclovir sodium in a patient with the acquired immunodeficiency syndrome. The viral isolate was shown to be resistant to acyclovir in vitro, but proved susceptible to vidarabine and foscarnet sodium (trisodium phosphonoformate). The patient failed to respond to a 2-week course of intravenous vidarabine. However, rapid improvement in the orofacial lesion occurred with intravenous foscarnet. Most HSV isolates that are resistant to acyclovir are spontaneous mutants partially or completely lacking in thymidine kinase. Because foscarnet is a direct inhibitor of HSV DNA polymerase, this compound is expected to have efficacy against acyclovir-resistant strains. This report documents successful treatment of clinically significant HSV with intravenous administration of foscarnet, suggesting that further study is indicated.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Drug Resistance, Microbial; Herpes Simplex; Humans; Male; Simplexvirus; Skin Diseases, Infectious

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cauda Equina; Ganciclovir; Humans; Male; Peripheral Nervous System Diseases; Syndrome

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Drug Therapy, Combination; HIV-1; Humans; Leukoplakia, Oral; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Drug Therapy, Combination; Humans; Male; Middle Aged; Neuromuscular Diseases; Time Factors; Zidovudine

Zidovudine was first prescribed for patients from the anti-human immunodeficiency virus (HIV) positive cohort of haemophiliacs in Newcastle in May 1987. Prior to this therapy, seven patients had died of acquired immune deficiency syndrome, and episodes of serious opportunistic infection were common. To date, 22 patients have received zidovudine, seven with or without acyclovir in a prospective Wellcome trial. Of the 22 patients, three were children and one was an adult female. All haemophilic patients were infected around 1982 as a result of factor VIII concentrate contamination with HIV. There have been five deaths, two occurring within 6 weeks of the start of zidovudine therapy. A third death was due to myocardial infarction in week 45. The other two deaths occurred at 41 weeks and 47 weeks in transfusion dependent patients. Only three serious opportunistic infections (pneumocystis pneumonia) have been observed in the remaining patients, one within a week of starting therapy and one in a non-compliant patient at week 24. The latter patients had a further episode of Pneumocystis carinii pneumonia in week 51. The transfusion dependent patients who died presented with anaemia at weeks 5 and 13, and required 48 and 28 units of packed cells respectively. A further patient required a single transfusion at week 7 and at week 43 continues to maintain an acceptable haemoglobin level.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Blood Coagulation Factors; Child; Child, Preschool; Drug Therapy, Combination; Female; Hemophilia A; Hemophilia B; Humans; Male; Opportunistic Infections; Pneumonia, Pneumocystis; Prospective Studies; Time Factors; Transfusion Reaction; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Erythropoietin; Ganciclovir; HIV-2; Humans; New York City

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Ganciclovir; Humans; Infant; Opportunistic Infections

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Herpes Simplex; Herpes Zoster; Humans; Interferons; Thymidine; Zidovudine

Topics: Abscess; Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Drug Resistance; Herpes Simplex; Humans; Male; Simplexvirus; Thumb

A 43-year-old man with the acquired immunodeficiency syndrome had clinical evidence of multifocal disease of the brain, but computed tomography was negative. Magnetic resonance imaging revealed multifocal lesions, histologically proven to be caused by cytomegalovirus. Therapy with 9[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (BW B759U) resulted in stabilization of the patient's clinical disease and radiographic improvement of the lesions.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cytomegalovirus Infections; Encephalitis; Ganciclovir; Humans; Magnetic Resonance Imaging; Male

We report a case of recurrent varicella-zoster virus infection in a patient with severe acquired immune deficiency syndrome in whom the infection has become clinically unresponsive to treatment with acyclovir.

Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Acyclovir; Adult; Drug Combinations; Drug Therapy, Combination; Herpes Zoster; Herpesvirus 3, Human; Homosexuality; Humans; Immune Tolerance; Male; Recurrence; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Electroretinographic (ERG) investigations were performed in three AIDS patients. The first had cotton wool-like spots in both eyes (AIDS "retinopathy"). The second presented with the same changes in his right eye and an acute cytomegalovirus (CMV) in his left eye. In the third patient signs of healed peripheral retinochoroiditis were found. In CMV retinitis the retinal damage demonstrated by ERG correlated well with the ophthalmoscopic findings. As the ERG improved concurrently with Ganciclovir therapy, retinal function can be monitored by means of ERG controls. In the cases of AIDS "retinopathy" with only a few cotton wool-like spots and with healed peripheral retinochoroiditis, pronounced changes in the ERG were seen regularly; these were most probably caused by ischemia of the inner retinal layers.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Electroretinography; Ganciclovir; Humans; Opportunistic Infections; Retina; Retinitis

We examined three patients with AIDS who had large, sharply demarcated areas of thinned retina consistent with inactive cytomegalovirus retinitis and who were not treated with ganciclovir. These lesions appeared identical to clinically inactive areas of cytomegalovirus retinitis after effective antiviral treatment. All patients were receiving azidothymidine or ribavirin, or both, which have activity against the human immunodeficiency virus and which may improve immune function. All patients also received oral acyclovir at doses ineffective against cytomegalovirus retinitis.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cytomegalovirus Infections; Fluorescein Angiography; Fundus Oculi; Humans; Male; Retinitis; Ribavirin; Thymidine; Zidovudine

The eyes of an AIDS patient with cytomegalovirus (CMV) retinitis and pneumonitis who died while receiving maintenance therapy with the antiviral agent 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl] guanine (Ganciclovir) were obtained for pathological examination. While under treatment the patient had significant improvement but not complete regression of retinitis. Electron microscopic and immunofluorescent techniques revealed cytomegalovirus particles in the retina, sclera, iris, and ciliary body. These findings are consistent with a virostatic type of inhibition of CMV by this agent. They also suggest that CMV involvement in the eye and other organs may be more widespread than is clinically apparent in AIDS patients.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Ciliary Body; Cytomegalovirus; Cytomegalovirus Infections; Eye; Ganciclovir; Humans; Iris; Male; Retina; Retinitis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Enterocolitis; Ganciclovir; Humans; Immunoglobulins; Infant; Male

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cytomegalovirus Infections; Ganciclovir; Humans; Male; Remission, Spontaneous; Retinitis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adrenal Gland Diseases; Antiviral Agents; Chorioretinitis; Cytomegalovirus Infections; Encephalitis; Ganciclovir; Gastrointestinal Diseases; Humans; Pneumonia, Viral

Six patients (11 eyes) with virologically confirmed cytomegalovirus (CMV) retinitis involving the posterior pole of the eye were treated with a new drug, ganciclovir. Treatment with intravenous ganciclovir consistently halted progression of retinitis and produced improvement in measures of visual function. However, within three weeks after cessation of therapy renewed CMV activity and worsening of visual function were observed in most cases. Maintenance therapy with ganciclovir extended the period of remission from CMV retinitis.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Female; Fundus Oculi; Ganciclovir; Humans; Male; Middle Aged; Retinitis; Visual Acuity

The efficacy and toxicity of ganciclovir given by intravenous or intravenous plus intravitreal injection were studied in nine patients with cytomegalovirus (CMV) retinitis; seven with AIDS and two with drug induced immunodeficiency. Five patients had retinitis with macular involvement in six sighted eyes; six patients had only peripheral retinitis in seven eyes. In two patients (two eyes) with macular involvement intravenous plus intravitreal injection of ganciclovir preserved sight; intravenous infusion alone did not in four eyes of three other patients. In seven eyes (six patients) with peripheral retinitis vision was retained regardless of the route of ganciclovir treatment. Following intravenous ganciclovir drug levels in the vitreous fluid were 1.4-2.2 mmol/l, that is, 44 and 65% of the concomitant serum concentration. Clinically and at necropsy three eyes showed no evidence of toxicity from intravitreal injection of ganciclovir. All of five patients with AIDS who received intravenous ganciclovir for more than one week developed leucopenia. CMV retinitis of the macula may be benefited with minimal drug toxicity by intravitreal injection of ganciclovir. Treatment of peripheral CMV retinitis in patients with AIDS may be optional.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Immunosuppression Therapy; Injections, Intravenous; Leukopenia; Retinitis; Visual Acuity; Vitreous Body

The acquired immunodeficiency syndrome (AIDS) affects the ocular structures in several ways. Kaposi's sarcoma has been observed on the bulbar conjunctiva of the globe. Retinal complications, however, are of major concern. Cotton-wool spots are commonly seen in AIDS patients and are usually of no consequence, except that they must be distinguished from the early stages of cytomegalovirus (CMV) retinitis, seen in 20-40% of these patients. CMV causes a necrotic-type retinitis potentially leading to blindness. 9-[2-Hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine (DHPG) has been found effective in the short-term treatment of this disorder. It is planned to use AS101 in the regimen to see if a long-term cure from this disease can be affected. Care must be taken in handling ocular tissue of AIDS patients or the re-use of ophthalmic instruments touching the eye of AIDS patients since the human immunodeficiency virus has been found in these structures.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Cytomegalovirus Infections; Eye Diseases; Ganciclovir; HIV; Humans; Retinitis

We report the first published case (to our knowledge) of histopathologically documented acquired immunodeficiency syndrome-related cytomegalovirus (CMV) myelitis in which antiviral drug therapy was administered. Despite sensitivity of the patient's CMV isolate to therapy with both ganciclovir and foscarnet, use of neither of these agents halted progression of central nervous system CMV disease. Higher doses of these drugs or combination therapy may be required to treat acquired immunodeficiency syndrome-related CMV myelitis effectively.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Encephalomyelitis; Foscarnet; Ganciclovir; Humans; Male; Organophosphorus Compounds; Phosphonoacetic Acid

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Homosexuality; Humans; Injections; Male; Retinitis; Vitreous Body

Of 760 AIDS patients seen at San Francisco General Hospital in 1986, 5.7 per cent had retinitis and 2.2 per cent had gastrointestinal disease caused by cytomegalovirus. We reviewed the records of 44 patients treated with ganciclovir for culture-confirmed cytomegalovirus retinal (31 patients) or gastrointestinal disease (17 patients) or both (four patients) in 1986. Retinitis stabilized or improved during initial treatment with ganciclovir in 22 of 27 (81.5 per cent) patients. Following a median 10-day induction course, 16 patients with retinitis continued to have serial ophthalmologic assessments: eight patients were maintained on treatment and eight had maintenance treatment deferred. Before treatment, the two groups were comparable in age, Karnofsky scores, hematologic assessment, visual acuity, and history with respect to Pneumocystis carinii pneumonia. Retinitis did not progress for a median 53.8 days in the immediate maintenance group compared to 18.8 days for the deferred maintenance group (p = 0.01). In 17 patients with CMV gastrointestinal disease, nine of 14 (64 per cent) had resolution of pain and eight of 11 (73 per cent) had resolution of diarrhea when treated initially with ganciclovir. In both retinitis and gastrointestinal disease patients, ganciclovir decreased recovery of CMV from urine and blood markedly. Ganciclovir also caused a decrease in mean absolute neutrophil counts to about half of baseline values; decreases in mean platelet count and hemoglobin were also noted but were less than 25 per cent. Neutropenia severe enough to require dose adjustment (less than 800 cells/microliters) occurred in 31 per cent of patients receiving maintenance ganciclovir.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Gastrointestinal Diseases; Humans; Neutropenia; Opportunistic Infections; Retinitis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Drug Resistance, Microbial; Female; Foscarnet; Herpes Genitalis; Humans; Organophosphorus Compounds; Phosphonoacetic Acid; Simplexvirus; Thymidine; Zidovudine

On the basis of observation that acyclovir potentiates the in-vitro antiviral activity of 3-azido-2',3'-dideoxythymidine (also known as azidothymidine or zidovudine) against human immunodeficiency virus (HIV), we administered a regimen of azidothymidine and acyclovir to eight patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. An oral regimen of 100 mg of azidothymidine and 800 mg of acyclovir every 4 hours was in general well tolerated, with the principal toxicity being megaloblastic erythroid changes. The pharmacokinetics of the two drugs were independent of each other. Six patients received the drug combination for at least 10 weeks; all had increased numbers of T4+ lymphocytes (P = 0.028), and two of three assessable patients had reversal of anergy. Two patients tested positive for serum HIV p24 antigen at entry, but became negative with treatment. Data for this small group suggest that this drug combination can be tolerated in patients with severe HIV infections; this study can be used as a basis for larger studies of this drug combination.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Complex; Antiviral Agents; Drug Interactions; Drug Therapy, Combination; Hematologic Diseases; Humans; Male; Middle Aged; Nervous System Diseases; Pilot Projects; T-Lymphocytes, Helper-Inducer; Thymidine; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Enterocolitis, Pseudomembranous; Humans; Male; Middle Aged; Thymidine; Zidovudine

Acyclovir has become the treatment of choice for varicella-zoster virus (VZV) infections in immunocompromised individuals. This article describes a 4-year-old girl congenitally infected with human immunodeficiency virus who developed a continuous cutaneous infection with VZV that persisted over a 14-month period until her death. Initial episodes of varicella and zoster were responsive to acyclovir treatment; however, subsequent recurrences necessitated administration of multiple courses of acyclovir. Lesions became markedly hyperkeratotic, slow healing, and persistent despite acyclovir therapy. Numerous attempts to isolate virus from the lesions yielded only one isolate late in the course of therapy. This virus clearly demonstrated acyclovir resistance in vitro. Bizarre manifestations of VZV infection could present both diagnostic and therapeutic dilemmas. Prolonged acyclovir treatment of highly immunocompromised patients with acquired immunodeficiency syndrome and severe VZV may lead to the appearance of resistant virus.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Chickenpox; Child, Preschool; Drug Administration Schedule; Drug Resistance, Microbial; Female; Herpes Zoster; Humans; Immunization, Passive

Oral hairy leukoplakia was treated in six patients with (a) acyclovir (i.v. or p.o.), (b) 0.1% vitamin-A acid solution or (c) human beta-interferon-gel (10(5) I.E./g) in a total of 23 therapeutic courses. In 5/6 patients, acyclovir (7.5 mg/kg every 8 h i.v. or 5 x 400 mg p.o. over 5-10 days) led to partial (n = 1) or complete (n = 4) remission. After 1-6 months, however, the leukoplakia recurred in all cases. Vitamin-A acid solution (n = 3) led to remission in one and to improvement in the others. Human beta-interferon gel (n = 3) had no visible effect. The efficacy of acyclovir is further evidence of the concept that the Epstein-Barr virus is a major cause of oral hairy leukoplakia.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; AIDS-Related Complex; Drug Therapy, Combination; Humans; Infusions, Intravenous; Interferon Type I; Leukoplakia, Oral; Mouth Mucosa; Neoplasm Staging; Tretinoin

Patients who are homosexual, intravenous drug abusers, or have received multiple blood transfusions are at greater risk to contract the immunosuppressive disorders of acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC). These persons also have a greater chance of developing serious neurologic complications after an episode of Herpes zoster. We present two cases which emphasize the serious complications of Herpes zoster ophthalmicus in such patients. Since systemically administered acyclovir may shorten the disease course and reduce the complications of Herpes zoster in immunocompromised individuals, the authors favor treatment of all such patients who have Herpes zoster ophthalmicus with a seven-day course of high-dose (30 mg/kg/day) intravenous acyclovir. To minimize serious neurologic complications in such patients, treatment should be instituted immediately before the results of human immunodeficiency virus (HIV) testing are known.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Complex; Female; Herpes Zoster Ophthalmicus; Humans; Injections, Intravenous; Male; Middle Aged; Nervous System Diseases; Risk Factors

Plasma exchange was used in three cases of peripheral neuropathy of polyradiculoneuritis type in patients with AIDS. The neurologic lesion in the first case was due to a cytomegalovirus, and plasma exchange appeared to provide additional benefits (to antiviral treatment) during the first attack of polyradiculoneuritis. The peripheral neurologic disorders were probably related to the HIV itself in the other two cases, and plasma exchange was carried out only briefly because of the seriousness of the situation, which was unaffected. Although plasma exchange is possible, if particular technical precautions are taken, in patients with AIDS, the present series is too small for valid scientific evaluation.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Ganciclovir; HIV Seropositivity; Humans; Male; Middle Aged; Plasma Exchange; Polyradiculoneuropathy; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Administration, Oral; Counseling; Female; Herpes Genitalis; Humans; Male; Pregnancy; Pregnancy Complications, Infectious; Recurrence

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Anti-Bacterial Agents; Antitrichomonal Agents; Female; Genital Neoplasms, Female; Gonorrhea; Humans; Lice Infestations; Lymphogranuloma Venereum; Lymphoma; Pregnancy; Pregnancy Complications, Infectious; Sarcoma, Kaposi; Sexually Transmitted Diseases; Syphilis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Agranulocytosis; Anti-Infective Agents; Humans; Leukocyte Count; Male; Neutropenia

Genital herpes simplex infection is a common and troublesome condition that is more often due to herpes simplex type II virus than to type I virus. The first step in management is accurate diagnosis by virus culture or antigen recognition. General management involves explaining the natural history to the patient, giving advice on sexual behavior, contact tracing, and hygiene. Oral or intravenous acyclovir provides the most useful therapy for first attacks. Acyclovir cream has a similar effect with external lesions in mild attacks. A course of acyclovir, however, has no effect on subsequent recurrence. Recurrent attacks, being brief compared with first attacks, are less influenced by acyclovir therapy, which should be given early for maximal effect. Oral and intravenous therapy are effective in the treatment of genital and anal herpes simplex infection in patients with acquired immune deficiency syndrome. When oral therapy is used, doses may need to be increased. Acyclovir therapy is a valuable development compared with previously available antivirals for genital herpes simplex infection.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Female; Herpes Genitalis; Humans; Immune Tolerance; Male; Pregnancy; Pregnancy Complications, Infectious; Recurrence

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus; DNA, Viral; Drug Resistance, Microbial; Herpesvirus 3, Human; Herpesvirus 4, Human; HIV; Humans; Interferons; Nucleosides; Reverse Transcriptase Inhibitors; Ribavirin; RNA, Messenger; RNA, Viral; Simplexvirus; Thymidine; Virus Diseases; Virus Physiological Phenomena; Virus Replication; Zidovudine

Ganciclovir is a nucleoside analog which inhibits the replication of herpesviruses in vitro and which has been effective by intravenous administration for the treatment of severe cytomegalovirus infection in immunocompromised patients. Because most patients with acquired immunodeficiency syndrome and severe cytomegalovirus infection have required lifelong daily suppressive ganciclovir therapy to control disease progression, oral therapy appears to have practical advantages. We studied the pharmacokinetics of orally administered ganciclovir in four patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis. Repeated oral ganciclovir doses (10 to 20 mg/kg every 6 h) were well tolerated. With a 20-mg/kg dose given every 6 h, mean steady-state peak and trough levels were 2.96 and 1.05 microM, respectively, and the area under the concentration-time curve from 0 to 24 h was 47 microM X h. Calculated absorption was 3.0%, based on urinary excretion. Because the levels achieved in serum with oral ganciclovir approximated those required to inhibit cytomegalovirus in vitro, a trial of oral maintenance therapy in immunocompromised patients with severe cytomegalovirus infections seems warranted.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Tolerance; Ganciclovir; Humans; Kinetics; Leukocyte Count; Retinitis

Eighteen immunocompromised patients with cytomegalovirus (CMV) retinitis were treated with ganciclovir, an investigational antiviral drug. CMV retinitis in association with acquired immune deficiency syndrome (AIDS) developed in 17 patients; CMV retinitis developed in one patient after cardiac transplantation. Fourteen patients responded to ganciclovir treatment with improvement in CMV retinitis. In 11 patients, the response was classified as complete; in three patients, the response was partial. Continued improvement in the retinitis was often seen while the patient was on maintenance treatment. Maintenance ganciclovir therapy was required; relapse occurred in five of seven patients in whom ganciclovir treatment was interrupted. The major limiting toxic side effect of ganciclovir was neutropenia, which necessitated temporary discontinuation of ganciclovir in five patients but was reversible in all cases. Ganciclovir appears to be an effective therapy for CMV retinitis, but chronic maintenance therapy is required.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Cytomegalovirus Infections; Eye; Ganciclovir; Humans; Recurrence; Retinitis

A total of 66 eyes in 41 patients were treated for cytomegalovirus (CMV) retinitis with a new acyclic nucleoside, ganciclovir (BW B759U). At the completion of the short-term therapy period of 21 days, 87.7% of eyes had stabilized or improved. Seventy-two percent of eyes stabilized or improved during long-term home maintenance therapy. Leukopenia and increased liver function abnormalities were the most common adverse drug reactions seen in this series. Ganciclovir dramatically improved the quality of life in these patients, but clinical evidence suggests that it is a virostatic medication requiring indefinite long-term maintenance therapy.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Alkaline Phosphatase; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Leukocyte Count; Liver; Male; Middle Aged; Retinitis; Time Factors

Ganciclovir is an experimental antiviral drug with activity against human cytomegalovirus (CMV). Forty patients with acquired immune deficiency syndrome (AIDS) and CMV retinopathy were treated with ganciclovir on a compassionate protocol basis. Initial treatment doses ranged from 5.0 to 14.0 mg/kg/day for 9 to 26 days. Signs of drug response were a halt to enlargement of lesions, decreased opacification of retinal tissue, and resolution of hemorrhage and vasculitis. Complete response was seen in 88% of patients and incomplete response was seen in 9%. Vision improved or remained stable in 88% of patients. Initial treatment did not eradicate live virus from the eye. To prevent reactivation of disease, 26 patients received low-dose maintenance therapy ranging from 1.5 to 7.5 mg/kg/day, once or twice daily, 3 to 7 days per week. Reactivation of disease developed for unknown reasons in 50% of patients on continuous, uninterrupted maintenance therapy for longer than 3 weeks. Reversible neutropenia, requiring cessation of treatment, developed in 30% of patients on initial treatment and in 38% of patients on maintenance therapy. Rhegmatogenous retinal detachment was a late complication in seven patients. By reducing or delaying visual loss, ganciclovir appears to be useful in the management of CMV retinopathy in patients with AIDS.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Male; Middle Aged; Neutropenia; Retina; Retinal Diseases; Vision, Ocular

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Male; Retinitis

Three patients with acquired immunodeficiency syndrome (AIDS) and disseminated cytomegalovirus (CMV) infection were treated with a new antiviral agent ganciclovir [9(1,3-dihydroxy-2-propoxymethyl) guanine] (DHPG). All initially showed dramatic clinical improvement. In two patients, serial ophthalmoscopic evaluations documented cessation of active retinitis although at autopsy one patient had evidence of active retinitis adjacent to scar. Reappearance of cotton-wool spots in the fundi of the third patient suggested an early relapse of his CMV infection which was halted by retreatment with ganciclovir. Two of the three patients developed breakthrough infection while receiving once-daily maintenance therapy after periods of three to five months. One patient continued to show a response to retreatment with full doses twelve months later but died after 17 months of progressive CMV disease. The dose of the drug needed to maintain remission requires further study.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Male; Ophthalmoscopy; Retinitis

We present a case of cytomegalovirus (CMV) retinitis in an AIDS patient who survived for 10 months after the start of his ocular problems. The retinitis responded to dihydroxy propoxy methyl guanine (DHPG) but relapsed four to six weeks after each course of treatment with progressive retinal destruction. One relapse was therefore treated with trisodium phosphoformate hexahydrate (Foscarnet). There are few reports of the use of this drug in the treatment of CMV retinitis with AIDS, but it appeared to be less effective in our patient than DHPG, possibly because of poor penetration of the blood-ocular barrier. A final course of outpatient maintenance therapy with DHPG failed to prevent a preterminal relapse of the retinitis. Fundus photographs demonstrated the resolution and relapse of the retinitis associated with each course of treatment. Maintenance therapy with DHPG would appear to be necessary to prevent relapse, but the logistics of this are difficult, and the effective dosage of DHPG is as yet uncertain.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Foscarnet; Fundus Oculi; Ganciclovir; Humans; Male; Middle Aged; Phosphonoacetic Acid; Retina; Retinitis; Visual Acuity

A 33-year-old male with acquired immunodeficiency syndrome received ganciclovir for presumed cytomegalovirus retinitis. Although results of baseline liver function tests were abnormal, marked elevations of transaminases and alkaline phosphatase occurred when the drug was first instituted, as well as after rechallenge. These elevated laboratory values declined on each occasion that the drug was withdrawn. As no other toxic or infectious insults could clearly be incriminated in these acute, self-limited episodes of hepatic function abnormalities, ganciclovir was most likely responsible for the toxicity observed in this patient.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Chemical and Drug Induced Liver Injury; Cytomegalovirus Infections; Ganciclovir; Humans; Liver Function Tests; Male; Time Factors

A patient with acquired immune deficiency syndrome with bilateral cytomegalovirus retinitis was treated with intravitreal 200-micrograms/0.1-ml doses of ganciclovir (9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl]guanine). The ganciclovir serum and intravitreal concentrations were measured with an enzyme-linked immunosorbent assay and pharmacokinetic factors were determined. There was no evidence of systemic absorption of ganciclovir from the eye. The elimination half-life of ganciclovir from the vitreous was estimated to be 13.3 hours. The intravitreal concentration remained above the ID50 of cytomegalovirus for approximately 62 hours after a single injection. Clinically, the patient retained useful vision in his right eye for three months. A total of 28 intravitreal injections were given on an outpatient basis under topical anesthesia and were well tolerated. There was no evidence of retinal toxicity from the drug.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Injections; Male; Retinitis; Visual Acuity; Vitreous Body

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Male; Middle Aged; Retinitis

Asymptomatic retinal lesions were found on annual ophthalmic examination in a 38-year-old homosexual man with the acquired immune deficiency syndrome (AIDS). The lesions were compatible with cytomegalovirus retinitis and progressed. Treatment with 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) resulted in regression of the lesions and improvement in his overall clinical condition. The retinal lesions in AIDS are reviewed.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cytomegalovirus Infections; Ganciclovir; Humans; Male; Retina; Retinitis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Male; Thrombophlebitis

Seventeen patients with the acquired immune deficiency syndrome and cytomegalovirus retinitis were treated with the antiviral drug ganciclovir (9-[1,3-dihydroxy-2-propoxy-methyl]-guanine, DHPG). Eight eyes of five patients developed rhegmatogenous retinal detachment after initiation of treatment. Multiple breaks in areas of peripheral, healed, atrophic retina accounted for the detachments. All seven eyes that underwent surgery had extensive retinal detachments that were reattached with vitrectomy and silicone oil. Retinotomy and retinal tacks were necessary in two cases that were complicated by severe proliferative vitreoretinopathy. In the fellow eye of one patient, laser treatment was used prophylactically to wall off a peripheral patch of healed retinitis. Endoretinal biopsies and culture were taken in five eyes; evidence of persistent cytomegalovirus was seen in two cases despite concurrent and clinically effective antiviral therapy.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Complex; Antiviral Agents; Biopsy; Cytomegalovirus Infections; Follow-Up Studies; Ganciclovir; Homosexuality; Humans; Male; Middle Aged; Prospective Studies; Retina; Retinal Detachment; Retinal Perforations; Retinitis; Vitrectomy

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cytomegalovirus Infections; Ganciclovir; Humans; Male; Middle Aged; Recurrence; Retinitis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Colitis; Cytomegalovirus Infections; Ganciclovir; Humans; Male; Retinitis

Ganciclovir is a new antiviral compound (also called BW B759U, DHPG, BIOLF-62, and 2'NDG) that has been used for the treatment of cytomegalovirus (CMV) retinopathy in immunocompromised patients (bone marrow recipients or acquired immune deficiency syndrome [AIDS] victims). The authors studied the eyes of three AIDS patients with CMV retinopathy who died while receiving ganciclovir chemotherapy. Gross, microscopic, and ultrastructural studies of these cases showed varying degrees of retinal scarring and active CMV lesions at the margins of the scars. CMV antigens were localized in cells at all layers of retina at the border of the lesions and in isolated cells in a perivascular location within histologically normal appearing retina. These areas probably represent sites of recrudescence when the drug is discontinued. In situ hybridization using a cloned complementary DNA (cDNA) probe of human CMV corroborated the immunocytologic localization of the virus. Ultrastructural studies showed megalic syncytial cells containing mostly capsids exclusively in the cell nucleus. The cytoplasmic electron-dense membrane-bound bodies that have characterized untreated cases of CMV retinopathy were absent in the treated cases. An attempt to isolate CMV in tissue culture from the vitreous and retina of one of the cases yielded a negative result. Our results indicate that ganciclovir does not effectively eliminate CMV from the retina nor does it suppress expression of all viral genes. Ganciclovir appears to function by limiting viral DNA synthesis and subsequent packaging of viral DNA into infectious units, thereby acting as a virostatic chemotherapeutic agent.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Ganciclovir; Humans; Male; Retina; Retinal Diseases

A 15-month prospective study of 109 patients with the acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) was conducted. Cytomegalovirus (CMV) retinitis developed in 18 of these patients; they were treated with ganciclovir. Five other patients with CMV retinitis who were not part of the prospective study were also treated with ganciclovir. CMV retinitis frequently involved the peripheral retina. All 23 patients treated with ganciclovir showed clinical regression of retinitis, although breakthrough recurrence of CMV retinitis occurred in seven patients (30.4%) while on maintenance therapy with ganciclovir. During treatment, neutropenia (less than 1000 leukocytes/mm3) developed in three patients (13%). Ganciclovir is an effective means of therapy for CMV retinitis, but it must be given chronically to prevent reactivation. Breakthrough recurrences while on maintenance therapy are not uncommon, but can be successfully treated with more aggressive treatment with ganciclovir. In addition, the prognosis for survival of AIDS patients being treated with ganciclovir is improved when compared with that of untreated patients.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Male; Middle Aged; Neutropenia; Prospective Studies; Recurrence; Retinitis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Cytomegalovirus Infections; Ganciclovir; Humans; Injections; Retinitis; Vitreous Body

Viral infections, predominantly those of the herpes virus family, account for up to 16% of all clinically significant infections in AIDS patients. Acyclovir has provided successful treatment in AIDS patients suffering from severe herpes simplex and herpes zoster virus infections. Preliminary results are presented on newly developed acyclovir analogues. Desciclovir, an oral prodrug of acyclovir which is metabolized to acyclovir in vivo, allows treatment of virus infections per os, where high serum levels are needed, e.g. in Epstein-Barr virus infections. BW B759U, another analogue of acyclovir, has been used for the treatment of life-threatening or sight-threatening cytomegalovirus infections in AIDS patients. More than 80% of the patients treated for retinitis experienced stabilization or clinical improvement. Antiviral efficacy was demonstrated in 73% of the patients. Azidothymidine, a nucleoside analogue of thymidine, has been developed specifically to treat the HIV infection. Its antiviral activity is based on inhibition of reverse transcriptase. Phase I studies have demonstrated that azidothymidine is well tolerated. Its ability to cross the blood brain barrier makes it an attractive candidate for treatment of HIV. Trials to determine efficacy are in progress.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Herpes Simplex; Herpes Zoster; Herpesvirus 4, Human; Humans; Leukoplakia, Oral; Opportunistic Infections; Thymidine; Tumor Virus Infections; Virus Diseases; Zidovudine

9-(1,3-dihydroxy-2-propoxymethyl) guanine (ganciclovir) was used to treat 41 patients (median age, 37 years) with the acquired immunodeficiency syndrome and cytomegalovirus gastrointestinal infection. Sites of infection were the colon in 31, the esophagus in 5, the rectum in 4, and the small bowel in 1. Patients received ganciclovir, 5 mg/kg body weight, intravenously every 12 hours for 14 days. Clinical improvement was seen in 30 patients and virologic response in 32. Mainly hematologic toxicity occurred: moderate leukopenia (1000 to 1900/mm3) was seen in 7 patients and severe (less than 1000/mm3) in 1, and moderate neutropenia (500 to 1000/mm3) in 5 and severe (less than 500/mm3) in 1. A cutaneous rash developed in 2 patients. Median overall survival was 16 weeks (range, 2 to 56). Cytomegalovirus recurred in 13 patients; median time to recurrence was 9 weeks from the start of treatment. Ganciclovir may be effective in treating cytomegalovirus gastrointestinal disease in patients with the acquired immunodeficiency syndrome.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Colitis; Cytomegalovirus Infections; Digestive System Diseases; Esophagitis; Ganciclovir; Hematologic Diseases; Hormones; Humans; Intestine, Small; Male; Middle Aged; Prospective Studies; Rectal Diseases; Recurrence; Ulcer

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Leukoplakia, Oral; Male; Middle Aged; Retinitis; Tongue Neoplasms

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Drug Interactions; Herpes Simplex; Humans; Male; Sleep Stages; Thymidine; Zidovudine

Amantadine is well established as the preferred antiviral agent for the prophylaxis of influenza A and may also be beneficial therapeutically when used early in the course of the disease. Idoxuridine is applicable only in the treatment of herpetic keratitis. Currently, acyclovir is the most effective agent for the treatment of herpes simplex and varicella-zoster virus infections. Ribavirin has recently been released for use in aerosol form for severe respiratory syncytial virus infections that occur in infants and young children. Vidarabine, which previously was the drug of choice in the treatment of severe herpetic infections, has now been replaced by the more effective acyclovir. Ganciclovir, an experimental agent, has shown promise against cytomegalovirus infections in patients who have undergone kidney or liver transplantation, but its effects are only temporary in patients who have undergone bone marrow transplantation and patients with acquired immunodeficiency syndrome (AIDS) who have cytomegalovirus infections.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Amantadine; Antiviral Agents; Ganciclovir; Herpes Simplex; Humans; Idoxuridine; Influenza A virus; Influenza, Human; Ribavirin; Rimantadine; Thymidine; Vidarabine; Viruses; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Diterpenes; Humans; Leukoplakia, Oral; Retinyl Esters; Vitamin A

Herpes zoster has recently been reported in young patients with risk factors for AIDS. In high-risk patients under age 55, herpes may be the first manifestation of AIDS or AIDS-related complex. Dissemination of zoster does not appear to be greatly increased in this group, but corticosteroid therapy should be withheld.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Age Factors; AIDS-Related Complex; Herpes Zoster; Homosexuality; Humans; Male; Risk Factors

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Amantadine; Antiviral Agents; Chickenpox; Common Cold; Cytomegalovirus Infections; Herpes Simplex; Herpes Zoster; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Influenza, Human; Interferons; Ribavirin; Rimantadine; Thymidine; Vidarabine; Virus Diseases; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Herpes Zoster; Herpesvirus 4, Human; Humans; Leukoplakia, Oral; Male; Tumor Virus Infections

Eight immunosuppressed homosexual men with cytomegalovirus viremia--seven with serious bilateral retinitis, one with colitis in addition to retinitis, and one with pneumonitis only--were treated with a new acyclovir derivative, 9-(1,3-dihydroxy-2-propoxymethyl) guanine, which has excellent in-vitro activity against cytomegalovirus. All patients had virologic and clinical improvement, but substantial leukopenia developed in three patients. Both clinical relapses and viral relapses occurred frequently, usually within 30 days after cessation of treatment. 9-(1,3-Dihydroxy-2-propoxymethyl) guanine represents the first clinically and virologically effective agent for the treatment of cytomegalovirus disease, but more effective and less toxic therapeutic regimens for both acute and chronic use must be developed.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Agranulocytosis; Antiviral Agents; Colitis; Cytomegalovirus Infections; Ganciclovir; Hodgkin Disease; Homosexuality; Humans; Male; Pneumonia, Viral; Retinitis

Eight patients with cytomegalovirus retinitis in one or both eyes were treated with 9-(1,3 dihydroxy 2-propoxymethyl) guanine. Of the 14 eyes with retinitis, eight demonstrated more than 90% resolution, four had partial improvement, one failed to respond, and one could not be evaluated. Two of the eight patients had chemotherapy-induced immunosuppression and had ocular remissions for at least several months. The remaining six patients had AIDS or probable AIDS and relapsed in five weeks or less after discontinuation of therapy. Dihydroxy propoxymethyl guanine appears to be effective biologically in treating human cytomegalovirus retinitis without the development of unacceptable side effects but a single course of therapy is not capable of eradicating the virus.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cytomegalovirus Infections; Drug Evaluation; Female; Ganciclovir; Humans; Male; Middle Aged; Recurrence; Retinitis; Visual Acuity

The drug 9-(1,3-dihydroxy-2-propoxymethyl)-guanine (DHPG) was used to treat serious cytomegalovirus infections in 26 patients with underlying immunodeficiency (including 22 with the acquired immunodeficiency syndrome). In 17 of 22 patients in whom cytomegalovirus was virologically confirmed, clinical status improved or stabilized, although in 4 of them the status of some affected organs deteriorated or did not improve. Fourteen of 18 patients with adequate viral-culture data had clearing of cytomegalovirus from all cultured sites. Patients with cytomegalovirus pneumonia often responded poorly; four of seven died before completing 14 days of DHPG therapy. The condition of 11 of 13 patients with cytomegalovirus retinitis and 5 of 8 with gastrointestinal disease stabilized or improved. However, clinical and virologic relapses occurred in 11 of 14 patients (79 percent) when DHPG was discontinued. Neutropenia was the most frequent adverse reaction. We conclude that DHPG offers promise for the therapy of severe cytomegalovirus infections in some immunodeficient patients, but further study will be necessary to establish its efficacy and safety.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Child, Preschool; Cytomegalovirus; Cytomegalovirus Infections; Drug Evaluation; Female; Ganciclovir; Gastrointestinal Diseases; Humans; Immune Tolerance; Immunologic Deficiency Syndromes; Infant; Male; Middle Aged; Pneumonia, Viral; Recurrence; Retinitis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Cytomegalovirus Infections; Drug Administration Schedule; Ganciclovir; Humans; Male

Six patients (all male, five homosexual and one bisexual, 23 to 48 years old) with the acquired immune deficiency syndrome (AIDS) who had cytomegalovirus retinitis were treated with a new antiviral drug as a part of a prospective open-labeled trial for serious cytomegalovirus infections. The drug, 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl] guanine (referred to as dihydroxy propoxymethyl guanine), a new acyclic nucleoside antiviral agent similar in structure to acyclovir, produced positive results. These patients treated with dihydroxy propoxymethyl guanine (2.5 mg/kg of body weight every eight hours) showed regression and often disappearance of the lesions of cytomegalovirus retinitis during and for several weeks after therapy, usually with concomitant resolution of viral shedding. The cytomegalovirus retinitis recurred in four patients (the other two were lost to follow-up), but retreatment usually led to remission. Adverse drug toxicity (reversible granulocytopenia) occurred in two patients.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Male; Middle Aged; Retinitis

Recent reports have suggested a role for BW-B759U in the treatment of cytomegalovirus retinitis. The present study presents the ophthalmoscopic features in three treated patients, and examines the microscopic findings in the eyes of the first patient ever treated with BW-B759U for cytomegalovirus retinitis. Ophthalmoscopic findings of improvement on drug therapy included remission of perivascular infiltration, stabilization of the extent of the retinal area involved, and development of a pigmented chorioretinal scar in the involved area. Relapses occurred with cessation of therapy, and repeated courses of therapy were required. One patient developed a rhegmatogenous detachment with retinal breaks in an atrophic area of treated retinitis. Electron microscopic examination of the eyes of one patient disclosed the persistence of cytomegalovirus inclusions in retinal cells despite previous drug therapy. These findings suggest a virostatic action for BW-B759U.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cytomegalovirus Infections; Fundus Oculi; Ganciclovir; Humans; Male; Ophthalmoscopy; Retinitis

Cytomegalovirus (CMV) retinopathy, a relentlessly progressive disease that results in permanent blindness, is the most common opportunistic infection of the eye in patients with the acquired immunodeficiency syndrome. Twenty patients with the acquired immunodeficiency syndrome with CMV retinopathy were treated with a new, experimental, antiviral drug, 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl]guanine (BW B759U), in dosages ranging from 5.0 to 14.0 mg/kg/d for a ten- to 20-day course. In 19 patients (95%), treatment halted the progression of infection and decreased retinal opacification, hemorrhage, and vasculitis. Vision remained stable in most cases. Six patients received no additional treatment. Fourteen patients received continued treatment with a lower maintenance dosage. Retinal disease reactivated in all patients who did not receive maintenance therapy immediately after initial treatment, indicating persistence of live virus despite drug therapy. Reactivation of disease also developed in four (40%) of ten patients receiving continuous, uninterrupted maintenance therapy for longer than three weeks. Reversible neutropenia, requiring cessation of treatment, developed in five (25%) of 20 patients on initial treatment and five (36%) of 14 patients receiving maintenance therapy. Rhegmatogenous retinal detachment was a late complication in four patients. BW B759U appears to be useful in the management of CMV retinopathy by reducing or delaying visual loss.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Cytomegalovirus Infections; Drug Evaluation; Ganciclovir; Humans; Male; Middle Aged; Neutropenia; Retinal Diseases; Visual Acuity

Several different genital and non-genital HSV isolates were obtained from a patient with an acquired immune deficiency of unknown aetiology. The patient was initially treated with topical acyclovir (ACV) and later with topical and intravenous ACV. In spite of treatment with antiviral drugs the patient continued to shed virus and to have extensive genital ulcerations. Restriction endonuclease (RE) analyses of the viral DNA revealed that all the isolates had characteristic HSV-2 patterns and that there were three genetically distinct virus groups among the ten isolates tested. Three post-therapy isolates, with the same RE pattern, were found to be devoid of thymidine kinase activity (TKD), highly resistant to ACV in cell culture, but sensitive to vidarabine (ara-A), phosphonoacetate and phosphonoformate. Two of these TKD isolates were obtained during and after topical ACV therapy and before intravenous treatment. Mice inoculated intracerebrally with a lethal dose of each of the three TKD viruses were refractory to ACV, but responded to vidarabine or a combination of ACV and ara-A. Mice inoculated with the TK+ viruses (including the pre-therapy isolate) responded to ACV and/or ara-A treatment. The results indicate that: (i) TKD variants may be produced in humans after topical ACV therapy; (ii) different ACV-resistant or sensitive HSV-2 variants can establish latency at different body sites and reactivate; and (iii) when drug-resistant viruses are isolated from patients with multiple reactivations, the drug in question should not be discontinued, since the patients may also be shedding drug-sensitive virus at a different body site.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Animals; DNA Restriction Enzymes; DNA, Viral; Drug Resistance, Microbial; Herpes Simplex; Humans; Mice; Opportunistic Infections; Simplexvirus

The ocular findings in 38 patients infected by the Human T Cell Lymphotropic Virus Type III (HTLV III) are reviewed. Twenty patients were suffering from the Acquired Immunodeficiency Syndrome (AIDS) and 18 from the HTLV III related disease Persistent Generalised Lymphadenopathy (PGL). Cotton wool spots were found in the retinae of 8 patients at some stage of their disease and the prognostic significance of these is discussed. Cytomegalovirus (CMV) Retinitis was an ocular complication in eight of the patients with AIDS. The therapeutic effects of a new anti-viral drug, di-hydroxy propoxymethyl guanine (DHPG), are discussed.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; AIDS-Related Complex; Antiviral Agents; Cytomegalovirus Infections; Eye Diseases; Fundus Oculi; Ganciclovir; Humans; Retinal Hemorrhage; Retinitis

Disseminated cytomegalovirus (CMV) infection is a common complication of the acquired immunodeficiency syndrome (AIDS) and contributes significantly to its morbidity and mortality. Dihydroxypropoxymethyl guanine, DHPG, is an antiviral agent that has been shown to inhibit CMV replication and to provide clinical benefit in patients with CMV infections, especially retinitis. In this study, the clinical characteristics, results of diagnostic evaluations, and survival were compared in 11 AIDS patients with disseminated CMV infections who were seen between August 1981 and October 1984 and were not treated with DHPG, and in 18 AIDS patients seen since that time who were treated with DHPG. The study groups were similar though the untreated group was somewhat more tissue depleted. Survival from diagnosis was significantly prolonged with DHPG therapy based upon life table analysis (p = 0.001). Therapy improved the quality of life, as 12 of 18 treated patients and only 2 of 11 untreated patients could be discharged from the hospital. Progression of CMV infection did not appear to play a role in the mortality of patients who died during DHPG therapy. We conclude that DHPG prolongs survival in patients with AIDS who have disseminated CMV infections.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans

The number of AIDS patients is still increasing. In 30-50% of these patients ocular lesions occur, which are of diagnostic and prognostic significance. If the life-span of AIDS patients lengthens in the future, adequate treatment of the ocular conditions will become increasingly important. The two most important ocular manifestations AIDS are CMV-retinitis and Kaposi's sarcoma of the conjunctiva. DHPG, a new virustatic for human cytomegalovirus, appears promising as treatment for the severe CMV-retinitis, which leads rapidly to blindness. Two case histories illustrate the preliminary results obtained with DHPG treatment. Kaposi's sarcoma of the conjunctiva is relatively benign is AIDS and can be treated successfully by surgical excision, radiotherapy, cryotherapy or local injections of cytostatics.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Chemical Phenomena; Chemistry; Conjunctival Neoplasms; Cytomegalovirus Infections; Ganciclovir; Humans; Male; Middle Aged; Retinitis; Sarcoma, Kaposi

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Dose-Response Relationship, Drug; Drug Synergism; HIV; Humans; In Vitro Techniques; Lymphocytes; Suramin; Virus Replication

In order to reveal the activity of polymorphonuclear neutrophil leukocytes (PMNL) representing the first step of defence against infections, measurements of chemiluminescence (CL) were performed in patients suffering from acquired immune deficiency syndrome (AIDS), lymphadenopathy, or hemophilia. In comparison with healthy controls, AIDS patients revealed significant reduction (about 50 per cent) of phagocytic, i.e. CL activity of neutrophils, which had been induced by Zymosan. Only part of the patients suffering from lymphadenopathy answered with decreased granulocyte activity on the application of Zymosan. If concanavalin A was used as stimulant of metabolic activity of PMNL-independently of phagocytosis-again AIDS and some of the lymphadenopathy patients showed a markedly reduced neutrophil response. In conclusion it should be stated that there is some evidence for at least two defects of cellular immunity associated with AIDS and to some extent, with AIDS-endangered homosexuals suffering from lymphadenopathy: first the defect of PMNL to answer to concanavalin A with increased metabolic activity, and secondly the defect of PMNL to start phagocytosis induced by Zymosan with a subsequent release of oxygen radicals which are measurable as chemiluminescence. The appraisal of granulocyte activity by means of measurements of chemiluminescence might become an additional criterion for AIDS diagnostics.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Anti-Infective Agents, Urinary; Concanavalin A; Drug Combinations; Hemophilia A; Humans; Immunoglobulins; Luminescent Measurements; Luminol; Lymphoproliferative Disorders; Male; Neutrophils; Phagocytosis; Sulfamethoxazole; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Zymosan

Cytomegalovirus infections can cause significant morbidity and mortality in immunosuppressed patients, and present antiviral agents have had little efficacy against these infections. We describe the use of an acyclic nucleoside 9-[2-hydroxy-1-(hydroxymethyl) ethoxy methyl]guanine (BW B759U), in the treatment of two patients with cytomegalovirus retinitis. The efficacy of this agent was evident, with healing of retinal lesions and resolution of viremia and viral shedding. BW B759U appears to be similar pharmacokinetically to intravenous acyclovir in terms of half-life, peak serum levels, and renal excretion.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Fundus Oculi; Ganciclovir; Half-Life; Humans; Male; Neutrophils; Retinitis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Male; Respiratory Tract Infections; Retinitis

Toxoplasmosis encephalitis developed in three male homosexuals with AIDS. Clinical symptoms of encephalitis began with a nonspecific organic mental syndrome. In two cases there developed late focal symptoms. There were light to moderately severe generalized EEG changes with additional focal signs. CSF findings and toxoplasmosis titres were not diagnostically altered. Computed tomography demonstrated multiple areas of decreased density in cortex and cerebellum. Administration of pyrimethamine and sulfamethoxydiazine to the three patients brought about clinical improvement within a few days and regression of abnormal CT changes within a few weeks of onset of treatment. One patient died after an encephalitis recurrence: autopsy demonstrated toxoplasma pseudocysts in immediate proximity to small necrotic foci in the brain. The possibility of toxoplasma encephalitis should be considered in AIDS patients who develop an organic mental syndrome. Often the diagnosis can only be made after response to a trial of toxoplasmosis treatment.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Candidiasis, Oral; Electroencephalography; Encephalitis; Homosexuality; Humans; Ketoconazole; Male; Tomography, X-Ray Computed; Toxoplasmosis

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Humans; Lymphatic Diseases; Male

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; Humans; Infusions, Parenteral; Male; Retinitis; Virus Diseases

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adolescent; Herpes Zoster; Humans; Immune Tolerance; Male