acyclovir and AIDS-Related-Opportunistic-Infections

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

We report the case of a 35-y-old HIV-infected female, who presented fulminant varicella hepatitis and recovered under medical treatment. Varicella zoster virus is an uncommon cause of acute liver disease which occurs mainly in immunocompromised patients. Acyclovir is the cornerstone of the treatment.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Female; Hepatitis, Viral, Human; Herpesvirus 3, Human; HIV Infections; Humans

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Anti-HIV Agents; Antifungal Agents; Antitubercular Agents; Antiviral Agents; Azithromycin; Chickenpox; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Famciclovir; Ganciclovir; Herpes Simplex; Humans; Mycobacterium avium-intracellulare Infection; Mycoses; Pneumonia, Pneumocystis; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary

Progressive outer retinal necrosis is a necrotizing herpetic retinopathy usually seen in immunocompromised patients. The authors describe two patients with this disease who initially had findings suggestive of an optic neuropathy. Vision declined after treatment with methylprednisolone, after which fundus examination became consistent with progressive outer retinal necrosis. These cases underscore the importance of careful examination of the retinal periphery before management of any presumed optic neuropathy with steroids.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Diagnostic Errors; Diplopia; Disease Progression; Encephalitis, Viral; Female; Foscarnet; Herpes Zoster; Humans; Magnetic Resonance Imaging; Methylprednisolone; Middle Aged; Necrosis; Optic Neuritis; Paresis; Prednisone; Retina

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Infective Agents; Antitubercular Agents; Antiviral Agents; Atovaquone; Azithromycin; Chickenpox; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Ganciclovir; Herpes Simplex; Humans; Mycobacterium avium-intracellulare Infection; Naphthoquinones; Pneumonia, Pneumocystis; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Valacyclovir; Valine

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-Infective Agents; Antifungal Agents; Antiprotozoal Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Antiviral Agents; Atovaquone; Azithromycin; Clarithromycin; Cytomegalovirus Infections; Drug Therapy, Combination; Famciclovir; Herpes Simplex; Herpes Zoster; Humans; Mycobacterium avium-intracellulare Infection; Mycoses; Naphthoquinones; Pneumonia, Pneumocystis; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Pulmonary; Valacyclovir; Valine

Topics: Acyclovir; Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Chickenpox; Chickenpox Vaccine; Child; Child, Preschool; Dose-Response Relationship, Drug; Humans; Immunization, Passive; Infant; Infant, Newborn; Infusions, Intravenous; Prognosis

Treatment of genital herpes requires accurate diagnosis, patient support, and effective treatment. Diagnosis is usually straightforward for classic presentations characterized by vesicular lesions but can be challenging for atypical presentations, which are more common. Diagnosis of asymptomatic infection requires access to molecular technology or type-specific serologic assays. Misconceptions about herpes simplex infection are common and patient education is essential. Patient concerns extend beyond disease frequency and severity-the psychological impact should not be underestimated. Antiviral therapy is relevant at all stages of infection. Acyclovir, valacyclovir, and famciclovir are effective and well tolerated for genital herpes treatment. Continuous suppressive therapy controls all symptoms of recurrent disease and helps to relieve disease complications. The prodrugs valacyclovir and famciclovir offer easier, less-frequent dosing than required for acyclovir. Valacyclovir achieves effective suppression when taken once a day. Interventions to prevent genital herpes transmission and to control the global problem are urgently required.

Topics: 2-Aminopurine; Acute Disease; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antibodies, Viral; Antiviral Agents; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Famciclovir; Herpes Genitalis; Herpesvirus 1, Human; Herpesvirus 2, Human; HIV Infections; Humans; Immunocompetence; Patient Education as Topic; Prodrugs; Secondary Prevention; Treatment Outcome; Valacyclovir; Valine

We report a case of a 28-year-old human immunodeficiency virus-positive man. He presented with confluent verrucous papules and nodules on his scrotum that were due to herpes simplex infection.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Diagnosis, Differential; Herpes Genitalis; Humans; Male; Scrotum; Valacyclovir; Valine

Human cytomegalovirus (HCMV) infects about 60% of adults in developed world and more than 90% of developing countries population. In the immunocompetent host, initial infection and reactivation of latent infection are usually asymptomatic. However, in hosts with impaired cellular immune functions, such as transplant recipients, patients infected with human immunodeficiency virus (HIV) or undergoing anticancer chemo- and/or radiotherapy, the full pathogenic potential of the virus may be realized. HCMV is also among the most common causes of viral intrauterine infection affecting from 0.4 to 2.3% of live-born infants. Though in pregnant, immunocompetent women infections with HCMV are usually asymptomatic, severe infections may occur among congenitally infected fetuses and infants due to immaturity of their immune system. Approximately 40% of mothers with primary HCMV infections during gestation transmit virus to their infants. Although only 10% of infected infants are symptomatic at birth, 20 to 30% of these die. In addition, 5 to 15% of asymptomatic neonates are at risk of developing congenital anomalies later. In this outline we present anti-CMV drugs currently in clinical use and give examples of new molecules under laboratory and clinical development.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Cidofovir; Cytomegalovirus Infections; Cytosine; Drugs, Investigational; Female; Foscarnet; Ganciclovir; Global Health; Humans; Infectious Disease Transmission, Vertical; Naphthalenesulfonates; Organophosphonates; Organophosphorus Compounds; Pregnancy; Pregnancy Complications, Infectious; Thionucleotides; Valacyclovir; Valganciclovir; Valine

Topics: Acyclovir; Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Chickenpox; Chickenpox Vaccine; Child; Child, Preschool; Dose-Response Relationship, Drug; Humans; Immunization, Passive; Infant; Infant, Newborn; Infusions, Intravenous; Prognosis

The management of genital herpes in patients infected with human immunodeficiency virus (HIV) differs from that in individuals with genital herpes because of the significant interaction between the two viruses involved. HIV-induced immunodeficiency increases the frequency and severity of recurrent anogenital herpes simplex virus (HSV) shedding and disease as well as the risk of developing drug-resistant HSV infection. HSV infection, in turn, increases HIV replication and the risk of HIV transmission. The advent of highly active antiretroviral therapy has facilitated therapy for genital herpes, but important unanswered questions remain about the optimal therapy of drug-sensitive and -resistant genital herpes and the role of antiherpes drugs in reducing HIV disease progression and the risk of HIV transmission.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Antiviral Agents; Drug Resistance; Foscarnet; Herpes Genitalis; HIV Infections; Humans; Recurrence; Risk Factors; Simplexvirus; Vidarabine

Varicella zoster virus (VZV) infections in human immunodeficiency virus (HIV)-infected patients are known to have a different disease spectrum from that seen in other types of patients. Varicella in children with HIV infection is likely to be more serious than in otherwise healthy children and routine antiviral therapy is recommended. There is evidence that the development of varicella in HIV-infected children is not associated with progression to AIDS, suggesting that it may be safe to immunize HIV-infected children with live attenuated varicella vaccine. There are no published data on varicella in HIV-infected adults, however, probably because most adults have already experienced varicella prior to HIV infection. Zoster in HIV-infected children differs somewhat from that in HIV-infected adults. In particular, HIV-infected children who develop varicella in the setting of severe immunodeficiency are at an especially high risk to develop zoster. Given the low rate of toxicity of aciclovir as well as its ease of administration and its efficacy in hastening the healing of VZV infections, prompt treatment with this antiviral agent is recommended for both HIV-infected children and adults. Foscarnet should be used for zoster that is strongly suspected or proven to be caused by aciclovir-resistant VZV. Patients with HIV for whom there is no evidence of significant immunosuppression and who have not had varicella should be immunized with live attenuated varicella vaccine as a preventative measure for both varicella and zoster. It is hoped that immunization of VZV seropositive HIV-infected patients will decrease the incidence of zoster. Studies to determine this are under way.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Chickenpox; Chickenpox Vaccine; Child; Foscarnet; Herpesvirus 3, Human; Humans; Prospective Studies; Risk Factors

With increasing use of acyclovir and ganciclovir, primarily due to the increased number of AIDS and transplant patients, further cases of neurologic toxicity will undoubtedly be encountered. Discontinuation or dosage reduction of acyclovir and ganciclovir is necessary to manage neurologic toxicity that is directly attributed to either agent. Renal dysfunction is a known risk factor for acyclovir neurotoxicity, and case reports indicate that renal dysfunction may also be a risk factor for ganciclovir neurotoxicity. Since ganciclovir is structurally related to acyclovir, clinicians should monitor for signs and symptoms of neurotoxicity as they would with acyclovir until the risk factors are more clearly defined. Dosage reduction for both agents and increased monitoring should occur when renal dysfunction is present, to minimize the risk of neurotoxicity and other serious adverse effects. Tables 1 and 2 summarize the recommended dosages of acyclovir and ganciclovir, respectively, in the presence of renal dysfunction. However, as a few case reports describe, neurotoxicity from these agents has also occurred in patients with normal renal function. Therefore, clinicians should always remain vigilant in monitoring for signs of neurotoxicity when acyclovir or ganciclovir is administered, and have a high index of suspicion for these agents if neurotoxicity is encountered during therapy.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Central Nervous System Diseases; Cytomegalovirus Infections; Ganciclovir; Herpes Simplex; Herpes Zoster; Humans; Renal Insufficiency; Risk Factors

Herpes zoster leukoencephalitis is a rare complication of varicella-zoster virus infection. Associated with high mortality, the majority of cases have been discovered postmortem; today, however, magnetic resonance imaging is being used successfully as an aid in the diagnosis of this disease. The first two reported cases of HIV-infected patients with herpes zoster leukoencephalitis who recovered clinically and showed complete resolution of the magnetic resonance demyelination images after acyclovir treatment are described. In addition, the cases of herpes zoster leukoencephalitis reported in the literature to date are reviewed.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Encephalitis, Viral; Herpes Zoster; Humans; Male

Herpes simplex viruses (HSV) 1 and 2 are responsible for genital herpes which is usually recognized as vesicles that ulcerate and eventually heal but recur periodically. Atypical genital herpes is often described in immunocompromised patients and can present as large, chronic, hyperkeratotic ulcers. Acyclovir-resistant HSV is occasionally isolated from such ulcers. Most cases of HSV infection reproduce subtle signs and symptoms, or more commonly, asymptomatic viral shedding. Such subclinical presentations may be responsible for most of the 30% increase in the prevalence of genital herpes in the United States during the past two decades.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Chronic Disease; Drug Resistance, Microbial; Herpes Genitalis; Herpesvirus 2, Human; Humans; Immunocompromised Host; Keratosis; Prevalence; Recurrence; Simplexvirus; Ulcer; Virus Shedding

Viral lesions of the mouth in patients with HIV infection are common and these diseases any be a marker for HIV and disease progression. We review the spectrum of oral viral manifestations and discuss treatment modalities. The most common Epstein-Barr virus (EBV)-induced disorder in HIV-infected patients is oral hairy leukoplakia. EBV-related oral B-cell and T-cell lymphoma in AIDS patients has been described repeatedly. Herpes virus type 1 and rarely type 2 may lead to painful and resistant oral ulcers, and systemic treatment with acyclovir, valaciclovir or famciclovir is indicated. In acyclovir-resistant cases foscarnet is the treatment of choice. In recent years it has been documented that Kaposi's sarcoma, which often affects oral mucosa, is probably induced by herpesvirus type 8. Cytomegalovirus was found in 53% of cases with herpesviridae-induced mucosal ulcers as the only ulcerogenic viral agent in AIDS patients. In severe cytomegalovirus infection treatment with ganciclovir is helpful. Viral warts induced by different HPV may occur in the mouth. Several physical treatment modalities are possible in the oral mucosa. In AIDS patients mollusca contagiosa may occur as large and atypical lesions in the face and lips and rarely in the oral cavity. Cryotherapy is a bloodless treatment in such patients.

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Cytomegalovirus Infections; Disease Progression; Famciclovir; Foscarnet; Ganciclovir; Herpesviridae Infections; Herpesvirus 1, Human; Herpesvirus 2, Human; Herpesvirus 4, Human; Herpesvirus 8, Human; Humans; Leukoplakia, Hairy; Lymphoma, B-Cell; Lymphoma, T-Cell; Molluscum Contagiosum; Mouth Diseases; Mouth Neoplasms; Oral Ulcer; Prodrugs; Sarcoma, Kaposi; Stomatitis, Herpetic; Tumor Virus Infections; Valacyclovir; Valine; Virus Diseases; Warts

More than 90% of patients with HIV have been infected at some time with cytomegalovirus (CMV) and up to 40% of those with advanced HIV will develop CMV disease. The incidence of CMV disease is increasing but the prognosis for the patient remains poor.. It is therefore important to monitor patients with low CD4+ counts in order to identify those most at risk of developing CMV disease and to treat them before the disease becomes established. Polymerase chain reaction (PCR) is probably the most effective and sensitive method of detecting CMV and a positive result is predictive for development of CMV disease; more than 80% of patients with CMV retinitis are CMV PCR-positive at the time of diagnosis. PCR can also detect the presence of CMV up to 14 months before the development of retinitis.. In patients with detectable CMV, but no evidence of active infection, pre-emptive treatment with ganciclovir or valaciclovir has been shown to reduce the risk of developing retinitis in these high-risk patients. Such oral therapy, which is generally better tolerated than intravenous therapy and results in a better quality of life for the patient, is likely to be more effective at this stage whilst viral loads are low.. CMV PCR can be used to prospectively monitor patients in order to identify those most at risk of developing CMV retinitis. If CMV infection is diagnosed early, while viral loads are still low, pre-emptive oral therapy can be instituted which will reduce the chances of developing retinitis in those patients most at risk.

Topics: Acyclovir; Administration, Oral; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Ganciclovir; Humans; Polymerase Chain Reaction; Risk Factors; Valacyclovir; Valine

It is well recognized clinically that herpesviruses can cause disease in AIDS patients once human immunodeficiency virus (HIV) has precipitated marked immunosuppression. However, in addition to this opportunistic relationship, there is evidence to suggest that herpesviruses could increase the pathogenicity of HIV by acting as cofactors. Experiments in vitro have shown that several herpesviruses can activate HIV gene expression or alter the cellular tropism of HIV through a variety of mechanisms (antigen presentation, cytokine release, pseudotype formation, CD4 cell surface upregulation, Fc receptor formation, transactivation). Studies of human autopsy material have shown that some herpesviruses (particularly cytomegalovirus, human herpes virus 6 and herpes simplex virus) are found frequently in AIDS patients. If such herpesviruses act as cofactors in vivo, then their inhibition by aciclovir could explain why a survival benefit has been reported from the use of this drug in two double-blind, placebo-controlled randomized trials.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Animals; Antiviral Agents; Gene Expression Regulation, Viral; Herpesviridae Infections; HIV-1; HIV-2; Humans; Randomized Controlled Trials as Topic

A case of a 9-year-old boy with AIDS and severe hairy leukoplakia on the tongue is reported. Clinically it appears as a bilateral whitish-grey, nonremovable lesion on the lateral margins of the tongue with characteristic vertical corrugations. The lesion failed to respond to topical and systemic antifungal treatment. In contrast, it completely disappeared after treatment with 600 mg acyclovir per day for 1 month. During the hairy leukoplakia development the CD4-lymphocytes count was 95/microL.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Child; Humans; Leukoplakia, Hairy; Male; Tongue Diseases

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

Herpes simplex virus (HSV) infections are very common in the general population and can be treated with the nucleoside analogue acyclovir. Acyclovir is initially phosphorylated intracellularly in HSV-infected cells by a viral-specific thymidine kinase to acyclovir-monophosphate. The monophosphate is subsequently di- and triphosphorylated by host cellular kinases to the active form of the drug, which inhibits HSV DNA polymerase and incorporates into the elongating viral DNA and causes chain termination. Acyclovir resistance has been increasingly described and is caused by mutations in either the thymidine kinase or the DNA polymerase genes. These mutations result in decreased or absent HSV thymidine kinase production, altered affinity of the thymidine kinase for acyclovir-triphosphate, or altered affinity of the HSV DNA polymerase for acyclovir-triphosphate. Thymidine kinase deficiency accounts for approximately 95% of acyclovir-resistant isolates. Clinical disease due to acyclovir-resistant HSV occurs primarily in immunocompromised patients and is usually characterized by a chronic, progressive ulcerative mucocutaneous disease with prolonged shedding of virus. Several large surveys have been done in an effort to determine the incidence of in vitro and clinical acyclovir resistance. Among immunocompetent hosts, even those who have received > or = 6 years of continuous acyclovir, the prevalence of acyclovir-resistant isolates has remained stable at approximately 3%. Only three cases of clinical resistance of HSV to acyclovir have been reported. However, the incidence in immunocompromised patients, particularly those with AIDS and those who have had bone marrow transplants, is increasing. Transmission of acyclovir-resistant isolates from person to person has not been documented, but due to the increased use of acyclovir and newer drugs, such as famciclovir, there is great concern that this transmission might occur in the future. Continued surveillance in both immunocompetent and immunocompromised hosts for the development of clinical acyclovir-resistant HSV disease is necessary.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Drug Resistance, Microbial; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Immunocompromised Host; United States

Most antiviral drugs are nucleoside analogues with potential teratogenic, embryotoxic, carcinogenic and antiproliferative activities. They must be administered with caution during pregnancy, because some are known teratogens (e.g. amantadine) and a similar propensity cannot be entirely excluded for others (e.g. aciclovir). Their adverse effects mostly involve bone marrow depression (e.g. granulocytopenia with ganciclovir, anaemia with zidovudine) or neurotoxicity (e.g. seizures with interferon-alpha, peripheral neuropathy with zalcitabine), although gastrointestinal effects are also seen. Idiosyncratic reactions include didanosine-induced acute pancreatitis. Only inosine pranobex is largely free from toxicity. Idoxuridine must be administered topically, given the severity of its systemic adverse effects. Drug interactions involving antiviral agents mostly reflect shared toxicity with other agents (e.g. neutropenia with ganciclovir and zidovudine, pancreatitis with didanosine and alcohol), although renal excretion or hepatic metabolism may be implicated. Given the possibility of severe adverse reactions and drug interactions, antiviral chemotherapy should only be used for potentially serious virus infections. Topical administration avoids systemic adverse effects but not mutagenic risks, and may result in exposure of individuals other than the patient (e.g. aerosolised ribavirin).

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Amantadine; Antiviral Agents; Didanosine; Drug Interactions; Foscarnet; Ganciclovir; Humans; Interferon-alpha; Ribavirin; Rimantadine; Vidarabine; Zalcitabine; Zidovudine

Infection by the varicella-zoster virus (VZV) is frequent in patients infected by the HIV-1. Nonetheless, visceral involvement in addition to that of pneumonia is rare, despite the important immune dysfunction found among these patients.. Varicella pneumonia was diagnosed in 2 patients with HIV-1 infection who presented cough with high fever and a characteristic rash in addition to respiratory failure and a micronodular pattern on chest radiography. The medical literature is reviewed (MEDLINE).. An excellent clinical response was achieved with endovenous acyclovir treatment.. The authors underline how rare is varicella pneumonia in patients with HIV-1 infection. The appearance of a pustulous vesicular rash in the context of a febrile episode leads to suspicion of this diagnosis. The treatment of choice is endovenous acyclovir (5 mg/kg/8 h). Varicella pneumonia has also been described in children with HIV-1 infection. The possible increase in patients with varicella pneumonia with be assessed, due to the immunosuppressive state of these patients. Patients not having been in contact with the varicella-zoster virus are particularly susceptible to presenting primoinfection by this virus.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Chickenpox; Female; HIV-1; Humans; Male; Pneumonia, Viral

Most of the human herpesviruses have a unique relationship with the central nervous system. In this review we summarize recent developments in the establishment of viral latency, and discuss the nervous system illnesses instigated by direct viral cytopathic effect, by immune activation, and by neoplastic events. Special consideration is given to herpesvirus infections in the context of acquired immunodeficiency syndrome, and in association with neonatal infections. New diagnostic techniques and treatments are also summarized.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Central Nervous System Diseases; Central Nervous System Neoplasms; Herpesviridae; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Polymerase Chain Reaction; Tumor Virus Infections

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

An increasing number of antiviral agents are presently in various stages of development and testing, and an increasing number have recently been licensed for use in humans. These drugs have been used extensively to treat viral infections in immunocompromised individuals, and these studies indicate that for many antiviral agents the response to therapy is highly dependent on the integrity of the underlying host immune response. In particular, the response to zidovudine, acyclovir and ganciclovir in persons with HIV-1 infection is highly dependent upon CD4 number, which can be considered a surrogate marker for the state of host immune function in these subjects. Responses to interferons likewise can be shown to depend on the host immune response, with responses due to both direct antiviral effects of this agent as well as immunomodulatory effects mediated through interferon-induced upregulation of HLA molecule expression. The interdependence of host immunity with antiviral efficacy is underscored by the increased antiviral drug resistance in persons with advanced degrees of chronic immunosuppression, related to the higher level of viral replication and viraemia which occurs in the absence of an effective host immune response. Further definition of the precise mechanisms of these interactions should facilitate the rational design of antiviral agents and immunomodulatory therapies to improve treatment of viral infections.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus Infections; Drug Resistance, Microbial; Ganciclovir; Herpesviridae Infections; HIV Infections; HIV-1; Humans; Immunity, Cellular; Interferons; Major Histocompatibility Complex; Virus Diseases; Zidovudine

Human herpesvirus-8 (HHV-8) replication is a key factor in Kaposi sarcoma, primary effusion lymphoma, and Castleman disease pathogenesis. In vitro data suggest that antivirals inhibit HHV-8 replication, but little data exist in humans. Daily oropharyngeal swabs were analyzed from HIV/HHV-8 dually infected men enrolled in three previous clinical trials of valacyclovir and famciclovir for HIV-1 and/or HSV-2 suppression. Fifty-eight participants contributed 6,036 swabs. HHV-8 was detected in 1,128 (19%) of 6,036 swabs, including 618 (21%) of 2,992 on placebo, 323 (15%) of 2,221 on valacyclovir, and 187 (23%) of 823 on famciclovir. After adjusting for baseline HIV viral load and highly active antiretroviral therapy (HAART) use, an 18% reduction in HHV-8 shedding frequency (IRR 0.822; P = 0.011) was found in participants on valacyclovir and a 30% reduction (IRR 0.700; P < 0.001) on famciclovir. HAART was associated with an 89% (IRR 0.129; P = 0.048) reduction in HHV-8-shedding. Neither antiviral nor antiretroviral therapy was associated with decreased HHV-8 quantity. Valacyclovir and famciclovir were associated with modest but significant reductions in HHV-8 oropharyngeal shedding frequency. In contrast, HAART was a potent inhibitor of HHV-8 replication. Studies of whether antiviral therapy in combination with ART will prevent HHV-8-associated disease appear warranted.

Topics: 2-Aminopurine; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Antiviral Agents; Famciclovir; Herpesviridae Infections; Herpesvirus 8, Human; HIV-1; Humans; Male; Middle Aged; Oropharynx; Valacyclovir; Valine; Viral Load; Virus Replication

Most persons who are infected with human immunodeficiency virus type 1 (HIV-1) are also infected with herpes simplex virus type 2 (HSV-2), which is frequently reactivated and is associated with increased plasma and genital levels of HIV-1. Therapy to suppress HSV-2 reduces the frequency of reactivation of HSV-2 as well as HIV-1 levels, suggesting that suppression of HSV-2 may reduce the risk of transmission of HIV-1.. We conducted a randomized, placebo-controlled trial of suppressive therapy for HSV-2 (acyclovir at a dose of 400 mg orally twice daily) in couples in which only one of the partners was seropositive for HIV-1 (CD4 count, > or = 250 cells per cubic millimeter) and that partner was also infected with HSV-2 and was not taking antiretroviral therapy at the time of enrollment. The primary end point was transmission of HIV-1 to the partner who was not initially infected with HIV-1; linkage of transmissions was assessed by means of genetic sequencing of viruses.. A total of 3408 couples were enrolled at 14 sites in Africa. Of the partners who were infected with HIV-1, 68% were women, and the baseline median CD4 count was 462 cells per cubic millimeter. Of 132 HIV-1 seroconversions that occurred after randomization (an incidence of 2.7 per 100 person-years), 84 were linked within couples by viral sequencing: 41 in the acyclovir group and 43 in the placebo group (hazard ratio with acyclovir, 0.92, 95% confidence interval [CI], 0.60 to 1.41; P=0.69). Suppression with acyclovir reduced the mean plasma concentration of HIV-1 by 0.25 log(10) copies per milliliter (95% CI, 0.22 to 0.29; P<0.001) and the occurrence of HSV-2-positive genital ulcers by 73% (risk ratio, 0.27; 95% CI, 0.20 to 0.36; P<0.001). A total of 92% of the partners infected with HIV-1 and 84% of the partners not infected with HIV-1 remained in the study for 24 months. The level of adherence to the dispensed study drug was 96%. No serious adverse events related to acyclovir were observed.. Daily acyclovir therapy did not reduce the risk of transmission of HIV-1, despite a reduction in plasma HIV-1 RNA of 0.25 log(10) copies per milliliter and a 73% reduction in the occurrence of genital ulcers due to HSV-2. (ClinicalTrials.gov number, NCT00194519.)

Topics: Acyclovir; Adolescent; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Female; Follow-Up Studies; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Patient Compliance; Pregnancy; RNA, Viral; Unsafe Sex; Young Adult

Epstein-Barr virus (EBV) replicates productively in oral hairy leukoplakia (HLP). One characteristic of human immunodeficiency virus (HIV)-associated HLP is a decreased oral epithelial Langerhans cell count. This prospective study tested the hypothesis that oral epithelial EBV replication decreases oral Langerhans cell counts. EBV replication in HLP was highly correlated with decreased oral Langerhans cell counts. Inhibition of EBV replication restored oral Langerhans cell counts to normal control levels, and the return of EBV replication after treatment resulted in a recurrent decline in oral Langerhans cell counts. Decreased oral Langerhans cell counts occurred independently of HIV infection, as demonstrated in HLP of otherwise healthy HIV-seronegative individuals. These results support the tested hypothesis and suggest that EBV manipulates and evades the mucosal immune response in oral epithelial infection. This novel EBV strategy for eliminating oral Langerhans cells may facilitate the persistence of oral epithelial EBV and may contribute to the pathogenesis of HLP.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cell Count; Herpesvirus 4, Human; HIV Infections; Humans; Langerhans Cells; Leukoplakia, Hairy; Male; Middle Aged; Mouth; Valacyclovir; Valine; Virus Replication

Our objective was to evaluate valaciclovir for anogenital herpes in HIV-infected individuals using 2 controlled trials conducted before highly active antiretroviral therapy (HAART) was used. In Study 1, 1062 patients (CD4+ > or = 100 cells/mm(3)) received suppressive valaciclovir or aciclovir for one year and were assessed monthly. In Study 2, 467 patients were treated episodically for > or =5 days with valaciclovir or aciclovir and evaluated daily. Valaciclovir was as effective as aciclovir for suppression and episodic treatment of herpes. Hazard ratios [95% confidence interval (CI)] for time to recurrence for valaciclovir 500 mg twice daily and 1000 mg once daily vs aciclovir were 0.73[0.50, 1.06], P=0.10, and 1.31[0.94, 1.82], P=0.11. Valaciclovir 500 mg twice daily was superior to 1000 mg once daily, P=0.001. Valaciclovir 1000 mg twice daily was comparable to aciclovir on herpes episode duration (hazard ratio 0.92[0.75, 1.14]). Adverse events were similar among treatments. In conclusion, valaciclovir is a safe, effective, convenient alternative to aciclovir for HSV infection in HIV-infected individuals.

Topics: Acyclovir; Adult; Aged; AIDS-Related Opportunistic Infections; Antiviral Agents; Confidence Intervals; Double-Blind Method; Drug Administration Schedule; Female; Herpes Genitalis; HIV Infections; Humans; Male; Middle Aged; Recurrence; Simplexvirus; Treatment Outcome; Valacyclovir; Valine

Cytomegalovirus (CMV) disease is a common complication of patients with advanced human immunodeficiency virus infection. The aim of the present study, based on a case-cohort design, was to determine the predictive value of follow-up and baseline qualitative plasma CMV polymerase chain reaction (PCR) values for CMV end-organ disease in 378 patients (158 who progressed to CMV end-organ disease and 220 who did not develop CMV disease). These patients are part of the full AIDS Clinical Trials Group 204 multinational study (1227 patients), a randomized, controlled trial that compared the effects of valacyclovir with those of acyclovir for CMV disease prevention. Baseline PCR positivity was a significant risk factor for CMV disease progression (relative risk [RR], 1.81; 95% confidence interval [CI], 1.09-3.00). In multivariate analyses, time-updated PCR positivity was strongly associated with progression to CMV end-organ disease (RR, 4.42; 95% CI, 2.87-6.81). Change in cumulative PCR status was informative for the risk of subsequent CMV disease.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Case-Control Studies; Cytomegalovirus; Cytomegalovirus Infections; HIV Infections; Humans; Male; Multivariate Analysis; Polymerase Chain Reaction; Predictive Value of Tests; Risk Factors; Valacyclovir; Valine

To compare the efficacy and safety of 7 days' treatment with famciclovir 500 mg twice a day versus acyclovir 400 mg five times a day, for mucocutaneous herpes simplex virus (HSV) infection in HIV-infected individuals.. Randomized, double-blind, parallel-group study to demonstrate equivalence for the primary efficacy parameter.. Forty-eight hospital-based or specialist public-health clinics in 12 countries.. Two-hundred and ninety-three HIV-positive patients with recurrent HSV infection (orolabial or genital) starting treatment within 48 h of first appearance of herpetic lesions.. Proportion of patients developing new lesions during treatment (primary outcome measures); Time to complete healing of lesions, time to cessation of viral shedding, time to loss of lesion-associated symptoms, number of withdrawals due to treatment failure (secondary outcome measures).. Equivalence was defined prospectively and famciclovir was equivalent to acyclovir in preventing new lesion formation: new lesions occurred in 16.7% and 13.3% of patients, respectively [difference, 3.4%; 95% confidence interval (CI), -4.8-11.5]. The groups were comparable in time to complete healing (median 7 days for both groups; hazard ratio, 1.01; 95% CI, 0.79-1.29; P = 0.95), cessation of viral shedding (median of 2 days [hazard ratio = 0.93; 95% C.I. 0.68, 1.27; p = 0.64]), and loss of lesion-associated symptoms (median 4 days; hazard ratio, 0.99; 95% CI, 0.75-1.30; P = 0.93). Similar numbers in each group withdrew because of treatment failure. There were no differences between groups in the incidence of adverse events.. Famciclovir given twice a day is as effective and well tolerated as high-dose acyclovir for mucocutaneous HSV infections in HIV-infected individuals, and has the convenience of less frequent dosing.

Topics: 2-Aminopurine; Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Double-Blind Method; Famciclovir; Female; Herpes Simplex; HIV Infections; HIV Seropositivity; Humans; Male; Middle Aged; Prodrugs; Time Factors

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 efficacy and toxicity of foscarnet cream for the treatment of mucocutaneous herpes simplex virus lesions or lesions that were clinically unresponsive to systemic acyclovir treatment (median, 30.5 days) in AIDS patients were studied in a phase I/II, open-label, nonrandomized multicenter trial. In the study, 20 patients with advanced stages of AIDS were treated with foscarnet 1% cream five times a day for a mean duration of 34.5 days. Response of index lesions (n = 20) was judged to be completely healed (8 lesions), excellent (4 lesions), or good (1 lesion) in 65% of lesions. The median time to first negative herpes simplex virus culture of index lesion was 8 days. Among 15 patients with pain at baseline, 11 had complete resolution of pain and 2 had at least a 50% reduction. Clinical adverse events included skin ulceration (4 patients), application site reactions (3 patients), fever (3 patients), and headache (3 patients). Five (25%) patients developed new lesions due to herpes simplex virus at sites other than those being treated topically while enrolled in the study. Topical foscarnet 1% cream appears to be a safe and effective treatment for acyclovir-unresponsive mucocutaneous herpes simplex virus infection in AIDS patients.

Topics: Acyclovir; Administration, Topical; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Drug Eruptions; Drug Resistance, Microbial; Female; Foscarnet; Herpes Simplex; Humans; Male; Middle Aged; Safety; Skin Ulcer

Virus load is a major risk factor for disease in many human viral infections, especially human immunodeficiency virus (HIV) disease. The effect of cytomegalovirus (CMV) load on disease progression and the influence of antiviral chemotherapy on surrogate markers of replication was investigated in 310 patients with advanced HIV disease in a randomized controlled trial that compared the effects of valacyclovir with those of acyclovir. Sequential blood and urine samples were analyzed by polymerase chain reaction (PCR), for human CMV (HCMV) DNA. In multivariate analyses, elevated virus load in both blood and urine at baseline was associated with increased risk of HCMV disease (relative hazard, 1.49 and 1.44 per log increase, respectively). Elevated virus load in blood at baseline was also associated with a significantly shorter survival time (log rank, P=. 0001). In time-updated analyses, valacyclovir significantly suppressed the virus load in subjects who were PCR positive at baseline (in blood or urine), when compared with the combined acyclovir arms.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Analysis of Variance; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Disease-Free Survival; HIV Infections; Humans; Multivariate Analysis; Polymerase Chain Reaction; Prodrugs; Risk Factors; Survival Rate; Time Factors; Valacyclovir; Valine; Virus Replication

Cytomegalovirus (CMV) disease is a common complication of advanced human immunodeficiency virus (HIV) infection. Administration of oral valaciclovir, a valine ester of acyclovir, achieves sufficient plasma acyclovir levels to inhibit many clinical isolates. Acyclovir has been associated with enhanced survival in AIDS but not with CMV disease prevention. CMV-seropositive patients (1227) with CD4 cell counts <100/mm3 were enrolled in a randomized, double-blind trial. Valaciclovir, 8 g/day, was compared with acyclovir, 3.2 or 0.8 g/day, for CMV prevention; all three arms were compared for survival. The confirmed CMV disease rate was 11.7% among valaciclovir recipients and 17.5% in the pooled acyclovir arms, a 33% reduction in risk. Time to confirmed CMV disease was significantly longer for the valaciclovir group (P = .03). A trend toward earlier mortality for valaciclovir recipients was seen (P = .06). Toxicity and earlier medication discontinuation were more common in this group. Valaciclovir significantly reduces the risk of CMV disease. Further exploration of a better-tolerated dose is warranted.

Topics: Acyclovir; Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus Infections; Double-Blind Method; Female; Humans; Male; Valacyclovir; Valine

Samples of blood and urine were collected at baseline, week 4, and week 8 and then every 8 weeks from 310 patients entering a controlled trial of prophylaxis with valaciclovir versus acyclovir. Samples were tested under code by polymerase chain reaction (PCR) in one laboratory. The median number of samples collected from each patient was 5 for blood (range, 0-15) and 5 for urine (range, 0-15). Both baseline PCR viremia and PCR viruria were significantly associated with future cytomegalovirus (CMV) disease (P = .002 and P = .02, respectively). The greatest effect of valaciclovir on CMV disease was seen in patients who were PCR-positive in blood at baseline (P = .002), although a significant effect was also seen in those who were PCR-negative in urine (P = .02). Thus, PCR viremia provides prognostic information about CMV disease in AIDS patients, and valaciclovir showed activity as both a preemptive and prophylactic agent.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Double-Blind Method; Female; Humans; Male; Multivariate Analysis; Polymerase Chain Reaction; Prognosis; Valacyclovir; Valine; Viremia

The present randomized, double-blind, placebo-controlled, multicenter clinical trial was designed to compare the efficacy and tolerability of sorivudine [1-beta-D-arabinofuranosyl-E-(2-bromovinyl)uracil] and acyclovir for the treatment of dermatomal herpes zoster in human immunodeficiency virus (HIV)-seropositive patients. A total of 170 HIV-seropositive adults presenting with herpes zoster (confirmed by direct fluorescent-antigen testing and/or viral culture) were enrolled and randomized to receive a 10-day course of orally administered sorivudine (40 mg once daily plus acyclovir placebos) or acyclovir (800 mg five times daily plus sorivudine placebo). Patients were monitored daily to document the events of cutaneous healing, pain, zoster-related complications, and drug-related adverse events. Patients were reassessed on days 21 and 28 and then once monthly for 1 year. The primary efficacy endpoint was time to the cessation of new vesicle formation. Secondary efficacy endpoints included times to other events of cutaneous healing, resolution of pain, and frequency of dissemination and zoster recurrence. In a multivariate analysis, sorivudine was superior to acyclovir for reducing the times to the cessation of new vesicle formation (relative risk [RR] = 1.54, 95% confidence interval [CI] = 1.00 to 2.36; P = 0.049) and total lesion crusting (RR = 1.48, 95% CI = 1.07 to 2.04; P = 0.017). In a univariate analysis, there was a trend favoring sorivudine for the cessation of new vesicle formation (median of 3 versus 4 days; P = 0.07) and a significant advantage for time to total lesion crusting (median of 7 versus 8 days; P = 0.02). The time to the resolution of zoster-associated pain, the frequency of dissemination, and the frequency of zoster recurrence were not different between the two treatment groups. Both drugs were well tolerated. Sorivudine is an effective drug for the treatment of herpes zoster in HIV-infected patients and results in accelerated cutaneous healing when compared with acyclovir therapy.

Topics: Acyclovir; Adolescent; Adult; Aged; AIDS-Related Opportunistic Infections; Antiviral Agents; Arabinofuranosyluracil; Double-Blind Method; Female; Herpes Zoster; Humans; Male; Middle Aged; Quality of Life; Recurrence; Treatment Outcome

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus Infections; Double-Blind Method; Hemolytic-Uremic Syndrome; HIV Infections; Humans; Male; Middle Aged; Prodrugs; Prospective Studies; Purpura, Thrombotic Thrombocytopenic; Risk Factors; Valacyclovir; Valine

To determine if use of antiherpes drugs protects against the development of AIDS-associated Kaposi's sarcoma (KS), data from 935 homosexual men with AIDS from the Multicenter AIDS Cohort Study were analyzed. In nested case-control analysis, neither acyclovir use for human immunodeficiency virus infection (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.56-1.26; P = .39) nor acyclovir use for any indication (OR, 1.02; 95% CI, 0.76-1.38; P = .89) was associated with a reduced risk of KS as initial AIDS diagnosis. In longitudinal analysis, acyclovir was also not protective against developing KS as a late manifestation of AIDS (after initial non-KS AIDS diagnosis). Among men with cytomegalovirus disease, ganciclovir use (relative risk [RR], 0.56; 95% CI, 0.22-1.44; P = .23) and foscarnet use (RR, 0.40; 95% CI, 0.051-3.10; P = .38) were associated (although not significantly) with a reduced risk of KS. Thus, acyclovir use does not appear to reduce the risk of KS, but further study of other antiherpes drugs such as ganciclovir and foscarnet is warranted.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Bisexuality; Case-Control Studies; Foscarnet; Ganciclovir; Herpesviridae Infections; Homosexuality, Male; Humans; Longitudinal Studies; Male; Risk; Sarcoma, Kaposi

Twenty-six AIDS patients were enrolled in an open label pilot study to evaluate the efficacy and toxicity of topical 1 percent ophthalmic trifluridine solution for the treatment of chronic mucocutaneous herpes simplex virus disease unresponsive to at least 10 days of acyclovir therapy. Susceptibility testing to acyclovir, trifluridine, and foscarnet was determined by plaque reduction assay. Twenty-four patients were evaluable for efficacy and 25 for toxicity analyses. Seven patients (29 percent) had complete healing of lesions. The overall estimated median time to complete healing was 7.1 weeks. An additional seven patients had > or = 50 percent reduction in lesion area. The overall estimated median time to 50 percent healing was 2.4 weeks. Ten (42 percent) patients discontinued treatment for reasons other than primary treatment failure and seven (29 percent) for failure to respond to therapy. Baseline patient characteristics associated with greater reduction in lesion area included higher Karnofsky score (p = 0.05), fewer lesions (p = 0.07), smaller lesion area (p = 0.11), and trifluridine susceptibility (p = 0.07). Eight (33 percent) patients developed new lesions outside of the treatment area while on study, reflecting the local nature of this therapy. No dose-limiting toxicity attributable to trifluridine was reported. Given the limited options for the treatment of acyclovir-resistant herpes simplex disease, topical trifluridine may be a useful alternative in selected patients.

Topics: Acyclovir; Administration, Topical; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Chronic Disease; Drug Resistance, Microbial; Female; Herpes Simplex; Humans; Male; Middle Aged; Pilot Projects; Safety; Trifluridine

A study (ACTG 204) involving the effect of valacyclovir in preventing CMV disease in persons with advanced HIV infection (CD4 count under 100) was stopped because there were more deaths in the valacyclovir arm than in either (high dose/low dose) acyclovir arms of the study. There is no obvious explanation. It is believed the high doses of valacyclovir used were too high for this patient population; this may have led to side effects and resulting breaks in treatment that could have adversely affected survival. A greater survival effect may have been seen with acyclovir due to greater time on treatment, or greater consistency of treatment. However, two studies presented at the Human Retroviruses conference in Washington, D.C. failed to find a survival benefit of acyclovir. Further investigation into ACTG 204's design and findings are underway.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; CD4 Lymphocyte Count; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Ethics, Medical; Humans; Placebos; Survival Analysis; Valacyclovir; Valine

HIV-related treatment and prevention strategies for opportunistic infections presented at the 1995 International Conference on Antimicrobial Agents and Chemotherapy (ICAAC) are highlighted. Research highlights include valaciclovir for CMV prophylaxis, oral ganciclovir for preventing CMV, resistant CMV, and cidofovir (HPMPC) for CMV. Other topics discuss treatments of Mycobacterium avium complex, opportunistic infections and HIV viremia; and reports on the effects of influenza and pneumococcal immunizations on HIV viral load.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Bacterial Vaccines; CD4 Lymphocyte Count; Cidofovir; Clinical Trials as Topic; Cytomegalovirus Infections; Cytosine; Drug Resistance, Microbial; Ganciclovir; HIV; Humans; Influenza Vaccines; Mycobacterium avium-intracellulare Infection; Organophosphonates; Organophosphorus Compounds; Pneumonia; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; United States; Valacyclovir; Valine; Viremia

Questions are being raised about the efficacy of oral ganciclovir (Cytovene) in preventing cytomegalovirus (CMV), and the toxicity of valaciclovir, a derivative of acyclovir, when administered in high doses. Two government studies (Syntex 1654 and CPCRA 023) of oral ganciclovir have resulted in conflicting results. The studies are under investigation in an attempt to resolve the differences. CPCRA has led to concerns about Cytovene, including its potential for resistance and its relatively high cost. Another study shows two grams of valaciclovir, four times per day, produces the same blood levels as intravenous acyclovir. However, both are toxic levels and neither drug is viewed as particularly effective.

Topics: Acyclovir; Administration, Oral; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Ganciclovir; Humans; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome; Valacyclovir; Valine

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

A retired woman with left ophthalmic shingles of over 2 years' duration attended with bilateral vision loss and systemic upset. Acute retinal necrosis with detachment was detected on right fundus examination. Cataract in left eye precluded funduscopy. Ocular ultrasonography revealed fibrotic retinal detachment in the left eye. MRI brain and orbits also showed signals of retinal detachment. No abnormal MRI signal within the optic nerve or brain was found. Varicella zoster virus was detected in ocular aqueous and blood samples. High-dose intravenous acyclovir was administered. HIV test was positive with a very low CD4 count. Antiretroviral medications were prescribed. There was no recovery of vision. She was certified as blind, and social services were involved in seeking to provide alterations to her home in view of her severe disability. This case highlights the importance of suspecting HIV in patients with severe or chronic ophthalmic shingles. Images and implications for clinical practice are presented.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; Antiviral Agents; Blindness; Diagnosis, Differential; Female; Herpes Zoster; HIV Infections; Humans; Magnetic Resonance Imaging; Patient Safety; Retinal Detachment; Retinal Diseases; Retinal Necrosis Syndrome, Acute; Ultrasonography; Varicella Zoster Virus Infection

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Humans; Male; Middle Aged; Pneumonia, Viral; Tomography, X-Ray Computed; Treatment Outcome; Varicella Zoster Virus Infection

Incidence of brain infections in Human Immunodeficiency Virus (HIV) positive patients is reduced after the availability of current high active antiretroviral therapy (HAART). Herpes Simplex Virus type 2 (HSV-2) is an infrequent cause of encephalitis in HIV patients despite it is frequently involved in sexual transmitted infections. Here, we report a case of HSV-2 encephalitis occurring in a patient without full suppression of HIV replication within the brain. A 38 year-old HIV infected man was admitted to our department because of recurrent generalized seizure and fever during the previous 24 hours. Eight months before our observation the patient was switched from a protease inhibitor based regimen to a rilpivirine-based regimen without any evidence of HIV-RNA replication in the plasma. When the patient was admitted in our hospital, he was febrile and moderately confused, no deficit of cranial nerves was reported, motility was conserved, but he was unable to walk. Laboratory examinations performed at admission demonstrated an increase of cerebrospinal fluid (CSF) protein and cells with lymphocyte prevalence, and normal CSF glucose. HSV-2-DNA and HIV-RNA were present within CSF at admission. Nuclear Magnetic Resonance imaging of the brain revealed lesions of the medial part of both temporal lobes including hippocampus without any sign of bleeding. A 21-day course of acyclovir therapy was administered with consistent improvement of clinical findings and disappearance of HSV-2-DNA within CSF. After the episode, HAART was switched to a regimen with high CSF penetrability containing abacavir, lamivudine, darunavir and ritonavir. Twelve months after HSV-2 encephalitis neurologic evaluation was normal, but symptoms of depression were reported, HIV-RNA remained undetectable both in the plasma and CSF, and CD4+ lymphocytes were above 500/μL. No opportunistic infection was reported. Patients switched to regimen well tolerated such those containing rilpivirine, that have poor drug concentration within CSF could be considered at risk for opportunistic infection of the brain. Further larger investigation needs to confirm this finding.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; Darunavir; Dideoxynucleosides; Drug Substitution; Encephalitis, Herpes Simplex; Herpesvirus 2, Human; HIV Infections; HIV Protease Inhibitors; Humans; Lamivudine; Male; Rilpivirine; Ritonavir; Virus Replication

Acyclovir-resistant herpes simplex virus (HSV) infection is common in immunocompromised patients, but the course of such infection is little known. We describe the long-term follow-up of HIV-infected patients diagnosed once with acyclovir-resistant HSV infections. We retrospectively studied all HIV-infected patients between 2000 and 2010 diagnosed with virologically confirmed acyclovir-resistant HSV infection. Patients' socio-demographic and immunovirological characteristics were described. Response to foscarnet or cidofovir and recurrences were reported. Among 5295 HIV-infected patients, 13 (0.2%) were once diagnosed with an acyclovir-resistant HSV infection. Twelve patients were men, nine patients were of African origin. All patients reported previous acyclovir exposure and median CD4 count was 183 cells/mm(3) Ten patients presented exclusively with cutaneous lesions. Initially, 11 patients were treated with foscarnet and two with cidofovir. The median follow-up was 67 months (6-145). All patients recurred, 10 presenting at least one acyclovir-resistant HSV recurrence. The median number of acyclovir-resistant HSV recurrences per patient was 2 (0 - 5). Regarding the first and second recurrences, 7/13 (54%) and 5/11 (45%) HSV clinical isolates exhibited resistance to acyclovir, respectively. Acyclovir-resistant HSV infection prevalence was low in our cohort. The rate of acyclovir-resistant HSV episodes averaged 50% during the two first recurrences.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cidofovir; Cytosine; Drug Resistance, Viral; Female; Follow-Up Studies; Foscarnet; Herpes Simplex; HIV Infections; Humans; Immunocompromised Host; Male; Middle Aged; Organophosphonates; Retrospective Studies; Skin Diseases, Viral; Skin Ulcer; Socioeconomic Factors; Thymidine Kinase; Treatment Outcome

We present the case of a 42-year-old man with AIDS who had lost complete vision of his left eye for the past 15 days. MRI and brightness scan ultrasonography were performed on his eyes that suggested of endophthalmitis with dendritic involvement in the left eye. Viral DNA PCR was performed in aqueous humour sample that confirmed the presence of herpes simplex virus and showed a negative result for cytomegalovirus. The patient was treated with a high dose of oral acyclovir for 10 days and long-term topical acyclovir. Neodymium-doped yttrium aluminum garnet procedure was performed to clear up the cornea, and intraocular pressure was controlled with brimonidine and timolol maleate. The patient was diagnosed to have disseminated tuberculosis (tuberculoma of the brain) and was started with antituberculosis therapy. His condition improved significantly after the treatment, and keratitis in cornea started to clean up.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antitubercular Agents; Antiviral Agents; Endophthalmitis; Humans; Keratitis, Herpetic; Male; Tuberculosis

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

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cidofovir; Cytosine; Drug Resistance, Viral; Facial Dermatoses; Herpes Simplex; Humans; Injections, Intralesional; Male; Organophosphonates

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Herpes Genitalis; HIV Infections; HIV-1; Humans; Risk Factors; Viral Load

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Herpes Genitalis; HIV Infections; HIV-1; Humans; Risk Factors; Sexual Partners

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

Genital herpes, a viral infection caused by Herpes simplex virus (HSV), is the most common cause of genital ulceration. Patients with a severe decrease in cellular immunity, such as patients positive for Human immunodeficiency virus (HIV) infection, are more likely to develop atypical, severe, disseminated and/or chronic HSV infections. On the other hand, there is an increase incidence of HIV detection among patients positive for HSV infection, as genital ulcers represent a potential portal of entry of HIV into the host. A case of a 52-year-old homosexual man with a two-month history of multiple erythematous ulcerative lesions on the perianal area, the buttocks, and the third left finger is presented. According to the clinical history, the clinical findings and the laboratory results, a diagnosis of HSV infection was made and treatment with valaciclovir was started, which led to complete regression of lesions 30 days later. The atypical features of the herpetic lesions, along with a past history of atypical pneumonitis one year prior to our observation, prompted to a diagnosis of concurrent HIV infection, later confirmed by laboratory. Atypical and disseminated HSV infections occur relatively often in HIV+ patients. This article discusses clinical presentation, diagnosis and management of HSV infection in such cases.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Anal Canal; Antiviral Agents; Buttocks; Fingers; Herpes Genitalis; HIV Seropositivity; HIV-1; Homosexuality, Male; Humans; Immunocompromised Host; Male; Middle Aged; Valacyclovir; Valine

It has been reported that the diagnosis of multidermatomal herpes zoster in HIV-infected patients occurs at a lower CD4 level than zoster involving a single dermatome. Herein, we describe 3 cases of HIV-infected patients presenting with disseminated zoster at high CD4 counts and low HIV viral loads.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; CD4 Lymphocyte Count; Follow-Up Studies; Herpes Zoster; HIV Infections; Humans; Infusions, Intravenous; Male; Middle Aged; Risk Assessment; Sampling Studies; Severity of Illness Index; Treatment Outcome

We report a 31-year-old man with an obstructive bronchial lesion due to herpes simplex type 2 infection, who responded promptly to endoscopic resection and oral treatment with acyclovir. Exophytic lesions of the respiratory tract are rare, potentially life-threatening, but readily treated complication of herpes simplex virus infection in HIV-infected individuals.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Bronchial Neoplasms; Diagnosis, Differential; Herpes Simplex; Herpesvirus 2, Human; HIV Infections; Humans; Lung Diseases, Obstructive; Male; Radiography; Tomography Scanners, X-Ray Computed

To describe the course and complications of varicella zoster ophthalmicus (VZO) in patients attending an eye clinic in a community with a high HIV seroprevalence.. Prospective cohort study of consecutive patients presenting to a tertiary hospital eye clinic with VZO.. Patients recruited in 2001 and 2002 received standardized initial topical and systemic management, which was then modified according to complications. Information on the course and complications of the disease was entered in a database prior to statistical analysis.. Information on 102 patients who had 250 visits to the eye clinic was collected. HIV serology was positive, negative, and unknown in 66, 22, and 14 patients, respectively. The most common complication was uveitis (40/102). Median delay from onset of rash to starting acyclovir was 5 days. Complications were present in 33 patients at the first visit. Complications were commoner in patients with positive Hutchinson's sign and were less common at CD4 counts <200. At CD4 counts, > or =200 HIV infection had little effect on the course and complications of VZO. Timing of commencement of Acyclovir therapy within or after 72 h had no demonstrable effect on the incidence of new complications.. In a resource-limited setting, patients with the following characteristics should have immediate ophthalmic assessment: symptoms suggesting ocular complications or the presence of Hutchinson's sign. All VZO patients should receive antiviral therapy at the first doctor's visit even if they present >72 h after onset of the rash.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Corneal Ulcer; Drug Administration Schedule; Female; Herpes Zoster Ophthalmicus; HIV Seroprevalence; Humans; Male; Middle Aged; Prospective Studies; South Africa; Uveitis

Between 6000 and 7000 women in the United States infected with human immunodeficiency virus (HIV) give birth annually. It is well known that HIV-related immunosuppression significantly increases the risk for acquiring opportunistic infections (OIs). However, there is limited information regarding the relationship of pregnancy in the setting of HIV/AIDS infection, subsequent development of OIs, and maternal and fetal outcomes. A pregnant 36-year-old woman with AIDS was diagnosed with varicella zoster meningitis. Weight-based therapy with acyclovir was initiated with clinical improvement in symptoms. Care of a pregnant HIV-infected patient with an OI poses a unique diagnostic and therapeutic challenge for clinicians. Early diagnosis and initiation of appropriate treatment may provide an opportunity to improve both maternal and fetal outcomes.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Female; Follow-Up Studies; Gestational Age; Herpes Zoster; Humans; Labor, Induced; Meningitis, Viral; Monitoring, Physiologic; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Prenatal Care; Prenatal Diagnosis; Risk Assessment; Severity of Illness Index

We present a case of an ulcerative lesion of the genitalia starting one year before in a 33-year-old man. Histopathologic examination revealed herpes virus infection, which suggested the existence of cell-mediated immunodeficiency. Human immunodeficiency virus (HIV) infection was confirmed by ELISA and Western blot test. The patient was treated with intravenous acyclovir, which led to complete remission. We underline the importance of early detecting and diagnosing patients with similar clinical manifestation as a sign of significant underlying immunodeficiency.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Blotting, Western; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Herpes Genitalis; Herpesvirus 2, Human; Humans

To identify factors related to variations in the appearance of untreated AIDS-related cytomegalovirus (CMV) retinitis in severely immunodeficient individuals before the availability of highly active antiretroviral therapy (HAART) and to draw inferences regarding early events in the natural history of CMV retinitis based on clinical findings.. Retrospective, observational case series.. We evaluated a series of 100 adult patients with AIDS and newly diagnosed CMV retinitis before the HAART era who were not being treated with specific anti-CMV therapy. Demographic factors, ophthalmic findings, and the influence of drug therapy (zidovudine, acyclovir) on lesion characteristics were evaluated. Lesion border opacity was scored using a four-point scale of severity.. Lesions could be categorized by type (fulminant/edematous or indolent/granular) in only 66% of eyes. Severe lesion border opacity (4+) was related to presence of zone 1 lesions (P = .032) and greater extent of disease (P = .004). Acyclovir use was associated with less severe opacity (P = .029) and less zone 1 involvement (P = .016). Early lesions were adjacent to vessels in 73% of eyes; the fovea was involved in 13% of eyes.. Lesion location and drug use that affects virus activity may influence the severity of lesion border opacity, a measure that may be more useful than lesion type in future clinical studies of CMV retinitis. In contrast to earlier concepts, CMV retinitis does not seem to be a fovea-sparing disease. Findings in this study can serve as a reference for investigations into possible changes in CMV retinitis since the introduction of HAART.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Antiviral Agents; Cytomegalovirus Retinitis; Drug Therapy, Combination; Female; Humans; Male; Retrospective Studies; Zidovudine

To describe host characteristics (use of highly active antiretroviral therapy [HAART]; CD4+ T-lymphocyte count; HIV ribonucleic acid [RNA] blood level) of people who were diagnosed with AIDS-related cytomegalovirus (CMV) retinitis after HAART became available and to investigate effects of HAART on ophthalmic findings.. Retrospective, observational case series.. We collected demographic, medical, laboratory, and ophthalmic data for all patients with AIDS and newly diagnosed, untreated CMV retinitis from January 1997 through December 2000 at 10 sites in Los Angeles and Orange Counties, California.. The proportions of Hispanic and African-American patients were equivalent to or greater than their prevalences in the AIDS and general populations of Los Angeles County. Most patients (n = 80; 63.5%) were known to be receiving HAART at the time of CMV retinitis diagnosis; only 22 patients (17.5%) were HAART-naïve. Median CD4+ T-lymphocyte count was 15 cells/microl and median HIV RNA blood level was 103,000 copies/ml for all patients, but in 10 patients, CMV retinitis developed despite good immunologic and virologic responses to HAART. When compared with HAART-naïve patients, HAART-failure patients with CMV retinitis had more asymptomatic disease (P = .073), better visual acuity in the better eye (P = .003), more bilateral disease (P = .007), less zone 1 involvement (P = .042), and lower lesion border opacity scores (P = .054).. Most patients with AIDS and newly diagnosed CMV retinitis in an urban setting are HAART-experienced. HAART may influence characteristics of new CMV retinitis lesions at presentation, despite laboratory evidence of treatment failure, possibly because of residual CMV-specific immunity.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Antiviral Agents; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cytomegalovirus Retinitis; Drug Therapy, Combination; Female; HIV; Humans; Los Angeles; Male; Retrospective Studies; RNA, Viral; Urban Population; Zidovudine

We reviewed retrospectively the demographic, clinical, biological characteristics and outcomes of 11 patients with HSV meningitis.. Among the 11 patients, six were infected with HIV, four had a documented history of genital herpes, and one recurrent meningitis. In all cases, the onset of symptoms was abrupt, with severe headache and fever. On admission, 9/11 patients had severe meningismus; two patients had HSV anogenital ulcerations. CSF analysis showed in every case a significant increased of leukocytes with a lymphocytic pleocytosis, a mild elevated protein level and a normal glucose level. HSV was detected in the CSF in every case by PCR: the typing performed on six patients was positive in every case for HSV-2. Intravenous acyclovir (IV ACV) was started in 10/11 cases (range: 3-10 days), switched to valaciclovir (VACV) (range: 5-7 days); one patient was treated with ACV per os for 10 days. The total resolution of symptoms occurred within 48hours in every case. Two patients presented with recurrent HSV-2 meningitis in the next two months, with favorable outcome under IV ACV: a switch to long term VACV 500mg/day was prescribed without any recurrence. No patient presented with recurrence after a median follow-up of 30 months.. Early recognition and treatment might improve the outcome of such infections. Adjunctive oral VACV after IV ACV treatment seems to be associated with a good clinical response in patients presenting with HSV meningitis. The duration of such treatments, including prophylactic treatments to prevent recurrent episodes must be better documented.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Comorbidity; Disease Susceptibility; Encephalitis, Herpes Simplex; Female; Herpes Genitalis; Herpesvirus 2, Human; Hospitals, Urban; Humans; Male; Middle Aged; Paris; Recurrence; Retrospective Studies; Treatment Outcome; Valacyclovir; Valine

Topics: Acyclovir; Aged; AIDS-Related Opportunistic Infections; Drug Resistance, Viral; Drug Therapy, Combination; Eye Infections, Viral; Ganciclovir; Humans; Immunocompromised Host; Male; Prednisone; Retinal Necrosis Syndrome, Acute; Valganciclovir

We report a case of acquired immunodeficiency syndrome (AIDS)-associated, acyclovir-refractory genital herpes infection treated with topical imidazoquinoline therapy. The patient's plasmacytoid dendritic cells made a robust interferon- alpha response following in vitro stimulation with imidazoquinoline but not with herpes simplex virus. We hypothesize that disease resulting from defective herpes simplex virus-stimulated interferon- alpha may be overcome by stimulating intact alternative pathways.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Aminoquinolines; Antiviral Agents; Dendritic Cells; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; HIV-1; Humans; Imiquimod; Interferon Inducers; Male

Herpes Zoster is produced by reactivation of latent Varicella Zoster Virus from the dorsal root ganglion of sensory nerves. It is common in older individuals and rarely described in the pediatric age group. We report a case of recurrent herpes zoster in a 3-year-old HIV positive child involving T4 dermatome on the first occasion and subsequently involving T10 dermatome. The child responded well to oral acyclovir.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Chickenpox; Humans; Infant; Male; Recurrence

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Herpes Genitalis; HIV Seropositivity; Humans; Male; Postoperative Care; Treatment Outcome; Valacyclovir; Valine; Viral Load

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: Acyclovir; Adrenal Cortex Hormones; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Diagnosis, Differential; Female; Herpes Genitalis; Humans; Middle Aged; Valacyclovir; Valine; Viral Load

We report the clinical and histopathologic findings of bacillary angiomatosis involving the palpebral conjunctiva with concomitant infection by cytomegalovirus and Mycobacterium species in a patient with acquired immune deficiency syndrome. After debulking, the conjunctival tissue was studied with the use of light and electron microscopy; stains for bacteria, acid-fast bacilli, and Bartonella species; and immunohistochemical studies for cytomegalovirus and herpes simplex virus. We observed the typical histopathologic findings of bacillary angiomatosis, the presence of bacilli stained by the Steiner and Steiner method, and the electron microscopic demonstration of bacilli consistent with Bartonella species. Immunohistochemistry confirmed infection with cytomegalovirus, which had been suggested by characteristic cytologic abnormalities. Acid-fast bacilli were also found in the excised tissue. Patients with bacillary angiomatosis of the conjunctiva may have infections with multiple additional microorganisms.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Angiomatosis, Bacillary; Anti-Bacterial Agents; Antiviral Agents; Bartonella henselae; Conjunctiva; Conjunctival Diseases; Cytomegalovirus; Cytomegalovirus Infections; Drug Therapy, Combination; Eye Infections; Humans; Male; Mycobacterium Infections, Nontuberculous; Mycobacterium kansasii

Whereas valacyclovir is widely used and is recommended by some authors in moderately immunocompromised HIV-infected patients, its use has not been validated by clinical studies. We report a case of herpes zoster in an HIV-infected patient for whom neurologic complication was not avoided despite valacyclovir therapy. Clinical outcome was favorable after intravenous acyclovir. This case suggests careful monitoring of valacyclovir in HIV-infected patients is necessary.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Drug Monitoring; Electromyography; Herpes Zoster; Humans; Immunocompromised Host; Infusions, Intravenous; Male; Middle Aged; Patient Selection; Radiculopathy; Treatment Failure; Valacyclovir; Valine; Viral Load

This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Antiviral Agents; Cataract; Disease Progression; Drug Therapy, Combination; Fluorescein Angiography; Ganciclovir; Herpes Zoster Ophthalmicus; Humans; Male; Phacoemulsification; Retinal Necrosis Syndrome, Acute; Visual Acuity

A 37-year-old man with a three-year history of Acquired Immunodeficiency Syndrome was admitted with impaired consciousness, seizures and fever. He was on highly active antiretroviral therapy and on neurotoxoplasmosis secondary prophylaxis. Laboratory exams from two months before showed a CD4 cell count of 37/microL and a viral load of 230,000 copies/mL. Three months before admission he developed herpetic skin rash in the right trunk and acyclovir was added to his treatment regimen. On physical exam he was drowsy and had motor and sensory aphasia. The patient had elevated protein levels and normal pressure in the cerebrospinal fluid (CSF). Contrast enhanced computed tomography scan of the brain showed a hypodense lesion in the left parietal lobe, with poorly defined margins and no contrast enhancement. The magnetic resonance scan (MRI) showed multiple hyperintensities in T2-weighted image in white and grey matters and hypointense products of hemorrhage in both hemispheres and in the cerebellum. He was empirically treated with intravenous acyclovir and prednisone. Viral DNA of Varicella-zoster virus (VZV) was detected in the CSF by means of polymerase chain reaction (PCR) analysis. Acyclovir was continued for 10 days and the patient became well, with improvement of aphasia. We present a case of VZV encephalitis, confirmed by nested PCR, in a patient with suggestive MRI findings, who succeeded with treatment. VZV encephalitis is a rare opportunistic infection, occurring in 0.1 to 4% of AIDS patients with neurological disease; it is related to severe immunodeficiency and has a high mortality.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; DNA, Viral; Encephalitis, Varicella Zoster; Herpesvirus 3, Human; Humans; Male; Polymerase Chain Reaction

Nodules are exceptional manifestations of herpes simplex virus (HSV) infection in immunocompromised patients. Only two cases of nodular HSV-2 infection of the perianal region have been reported previously.. The case of a 46-year-old homosexual man with AIDS presenting with painful perianal nodules resembling squamous cell carcinoma is described.. This case report presents details of the histologic findings and treatment regimen.. Histologic examination showed the presence of rare multinucleated giant epithelial cells and a dense inflammatory infiltrate composed mostly of plasma cells. Polymerase chain reaction analysis was positive for HSV-2 and negative for HSV-1, cytomegalovirus, Epstein-Barr virus, and human herpesvirus types 6 and 7. After being treated ineffectively with oral acyclovir (4 g/d) for 15 days, the patient was treated with oral valacyclovir (6 g/d), resulting in marked improvement in 10 days and complete resolution after 2 months.. In immunocompromised patients, HSV-2 infection may present with atypical clinical and histopathological features.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Anus Diseases; Herpes Simplex; HIV Infections; Humans; Inflammation; Male; Middle Aged; Plasma Cells; Simplexvirus

Although a range of cytomegalovirus (CMV)-induced cutaneous manifestations is described in AIDS patients, skin involvement in immunocompromised patients is rare, and intraneural CMV inclusions or CMV neuritis has not been documented in skin biopsies.. Cutaneous biopsies of CMV lesions were collected prospectively for 12 months. The morphology, sites and symptomatology of the individual lesions, associated systemic illnesses, treatment schedules and disease outcome were recorded. A total of nine biopsies were obtained from three females who presented with extensive painful perineal ulceration and disseminated cutaneous ulcers, nodules and plaques. Clinically, herpes simplex virus (HSV) ulceration was diagnosed and treatment with acyclovir was initiated after biopsies from the natal cleft, perineum and neck were obtained. All were superficial and demonstrated HSV infection. Only the natal cleft biopsy demonstrated coexistent CMV inclusions. Suboptimal healing necessitated two further biopsies from each patient, none of which demonstrated HSV inclusions. Three of four deep perineal biopsies demonstrated CMV inclusions within nerves attended by a lymphocytic infiltrate and architectural disturbances. Two deep cutaneous biopsies of the trunk and abdominal wall confirmed CMV in extraneural locations only. One superficial perineal biopsy did not demonstrate any viral inclusion.. In documenting CMV neuritis in painful perineal ulcers, the histopathological spectrum of perineal CMV ulcers is expanded, a cutaneous neurotropic characteristic of CMV is presented and a direct role for CMV in the pathogenesis of pain is suggested. CMV latency within perineal nerves is also revisited as another potential site of CMV reactivation in immunocompromised patients, and another potential site for possible venereal transmission of CMV infection. The exclusive presence of HSV in initial superficial biopsies highlights the need for optimally biopsied tissue to confirm the coexistence of CMV infection.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Humans; Immunocompromised Host; Immunohistochemistry; Neuritis; Perineum; Prospective Studies; Skin Ulcer; Treatment Outcome

Mutations in the thymidine kinase (TK) and DNA polymerase (pol) genes of herpes simplex virus (HSV) may confer resistance to antiviral drugs, particularly in the context of immunosuppression induced by infection with the human immunodeficiency virus (HIV).. To characterise the HSV type 2 (HSV-2) TK and DNA pol genes in an immunocompromised patient with clinical resistance to both acyclovir and foscarnet.. The TK and DNA pol genes of isolates obtained over a 2-year period from an AIDS patient with severe genital herpes infection were characterised both phenotypically and genotypically.. HSV strains that were acyclovir resistant/foscarnet sensitive, acyclovir sensitive/foscarnet sensitive and acyclovir resistant/foscarnet resistant were isolated during this time. The TK gene of all the acyclovir resistant isolates contained a large 969 bp deletion which extended into a downstream untranslated region. The foscarnet resistance was associated with an S725G mutation in a conserved region (region II) of the herpesvirus DNA pol gene.. Clinical and virological suppression of the infection was not always associated with subsequent reactivation with wild-type virus. Mutations of the nature we describe have not previously been reported occurring simultaneously in HSV strains isolated from patients treated with acyclovir and foscarnet.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; DNA-Directed DNA Polymerase; Drug Resistance, Viral; Female; Foscarnet; Genes, Viral; Herpes Genitalis; Herpesvirus 2, Human; Humans; Immunocompromised Host; Microbial Sensitivity Tests; Molecular Sequence Data; Mutation; Sequence Analysis, DNA; Thymidine Kinase

Extensive reviews of pulmonary infections in AIDS have reported few herpetic infections. Generally these infections are due to Herpes simplex type 1. Pneumonia due to herpes type 2 is extremely rare. We describe a 40 year-old HIV positive woman who complained of fever, cough and dyspnea for seven years. She had signs of heart failure and the appearance of her genital vesicles was highly suggestive of genital herpes. Echocardiography showed marked pulmonary hypertension, right ventricular hypertrophy and tricuspid insufficiency. After a few days of hospitalization she was treated with Aciclovir and later with Ganciclovir. An open pulmonary biopsy revealed an interstitial inflammation, localized in the alveolar walls. Some pulmonary arteries had widened walls and focal hyaline degeneration. Immunohistochemistry indicated that the nuclei had herpes simplex virus type 2 in many endothelial cells (including vessels with widened walls), macrophages in the alveolar septa and pneumocytes. There was clinical improvement after treatment for herpes. We concluded that as a consequence of herpes infection, endothelial involvement and interstitial inflammation supervene, with thickening of vascular walls and partial obliteration of the vessel lumen. A direct consequence of these changes in pulmonary vasculature was pulmonary hypertension followed by heart failure.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cardiac Output, Low; Female; Ganciclovir; Herpes Genitalis; Herpes Simplex; Herpesvirus 2, Human; Humans; Hypertension, Pulmonary; Pneumonia, Viral

Two male patients aged 40 and 45 years with HIV infection and paraplegia are presented. The two had sub-acute onset paraplegia with a sensory level, which developed 10 days after herpes zoster dermatomal rash. They both had asymmetrically involvement of the lower limbs. Investigation including imaging of the spinal cord did not reveal any other cause of the neurological deficit. The two responded very well to treatment with acyclovir. Herpes zoster myelitis is a condition likely to rise with the upsurge of HIV infection and there is a need to identify the condition early. We also review the literature on the subject.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Diagnosis, Differential; Disease Progression; Herpes Zoster; Humans; Male; Middle Aged; Myelitis; Paraplegia; Time Factors; Treatment Outcome

Management of the increasing frequency of aciclovir-resistant herpes simplex virus (HSV) infections among immunocompromised human immunodeficiency virus-infected people demands additional treatment options. We report the case of a 38-year-old patient with acquired immune deficiency syndrome who suffered from a perianal butterfly ulcer, which was HSV-2 positive by polymerase chain reaction (PCR) analysis. The ulcer appeared during treatment of a cytomegalovirus (CMV) pneumonitis with ganciclovir. Despite additional valaciclovir therapy the lesion gradually progressed in size. Investigations including histology, PCR analysis and in situ hybridization of a biopsy from the growing ulcer margin confirmed the presence of HSV-2 infection. Importantly, HSV isolates from this specimen were resistant to aciclovir. Based on a report about the successful treatment of aciclovir-resistant HSV infection with cidofovir, our patient received this drug intravenously at a dose of 5 mg kg-1 body weight once weekly for a total of 3 weeks. Concomitant oral probenecid and prehydration were administered to minimize nephrotoxicity. Within 30 days of treatment the ulcer had almost (> 95%) completely healed. We conclude that cidofovir is a potent antiviral drug with a potential usefulness in the treatment of aciclovir-resistant HSV-2 infection. It deserves further investigation in clinical trials.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cidofovir; Cytosine; Drug Resistance, Viral; Female; Fissure in Ano; Herpes Simplex; Herpesvirus 2, Human; Humans; Organophosphonates; Organophosphorus Compounds

Central retinal vein occlusion (CRVO) due to herpes zoster has rarely been reported. Varicella zoster virus is a common opportunistic infection in patients with AIDS. This case report is about a 40-year-old man with herpes zoster ophthalmicus and central retinal vein occlusion of the right eye who is HIV-positive. Although the lesion resolved following treatment with intravenous acyclovir and oral steroid, the patient subsequently developed florid disc neovascularization and vitreous hemorrhage. The paper highlights CRVO as the initial presentation in an AIDS patient with herpes zoster ophthalmicus.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Drug Therapy, Combination; Glucocorticoids; Herpes Zoster Ophthalmicus; HIV Seropositivity; Humans; Male; Papilledema; Prednisolone; Retinal Neovascularization; Retinal Vein Occlusion; Vitreous Hemorrhage

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

In 1983, varicella zoster virus (VZV) disease was first recognized in the context of infection with the human immunodeficiency virus (HIV). Since that time, there have been many reports discussing the occurrence and clinical manifestations of hepes zoster in HIV-infected patients. We describe the development of prolonged herpes zoster in a patient with acquired immunodeficiency syndrome (AIDS) over the course of 104 days. Viral isolates at the three different clinical stages of the skin lesions were sensitive in vitro to acyclovir, and supposed to be a same strain by polymerase chain reaction (PCR) analysis. We also discuss an effective treatment for prolonged cases of zoster.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Back; Chronic Disease; DNA, Viral; Herpes Zoster; Humans; Male; Polymerase Chain Reaction; Skin Diseases, Viral

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

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; HIV-1; Humans; Keratitis, Herpetic; Male; Middle Aged; Prodrugs; Purpura, Thrombotic Thrombocytopenic; Recurrence; Valacyclovir; Valine

To evaluate the impact of antiretroviral and antiherpesvirus therapies on the incidence of KS and assess trends in incidence of Kaposi's sarcoma (KS) in a large multicenter HIV/AIDS surveillance system between 1990 and 1998.. Incidence was calculated per 100 person-years (py); the effects of therapies on risk for KS were calculated by using multivariate Poisson regression controlling for gender, race/ethnicity, age, HIV exposure mode, CD4+ cell count, and calendar year. Antiretroviral therapy was defined as monotherapy, dual therapy, or triple therapy (95% of triple therapy regimens contained a protease inhibitor). Acyclovir, ganciclovir, and foscarnet were the antiherpesvirus therapies evaluated.. There were 37,303 HIV-infected people in the study contributing 70,238 py. Those prescribed triple antiretroviral therapy had a 50% reduction in the incidence of KS (95% confidence interval, 20%-70%) compared with those who were not prescribed antiretroviral therapy and there was a reduction in risk for KS among persons prescribed foscarnet (p =.05). Overall, KS incidence declined an estimated 8.8% per year (observed incidence 4. 1 per 100 py in 1990 to 0.7 per 100 py in 1998; p <.001).. Incidence of KS is declining in this large U.S. population and may continue to decline as new, more effective antiretroviral agents are developed and used widely.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Drug Therapy, Combination; Female; Foscarnet; Ganciclovir; HIV Infections; Homosexuality, Male; Humans; Incidence; Male; Middle Aged; Multicenter Studies as Topic; Retrospective Studies; Risk Factors; Sarcoma, Kaposi; Skin Neoplasms

To evaluate the contribution of molecular methods for the diagnosis of an acyclovir-resistant HSV-1 bilateral keratitis in an AIDS patient and to report a new point mutation in the nucleotide sequence of the thymidine kinase (tk) gene involved.. A 31 year old HIV-positive female presented with severe, active, bilateral and sight-threatening keratitis of 6 months duration, which was treated unsuccessfully with acyclovir. After corneal biopsy, samples were analysed by standard virological procedures, in situ hybridization, and PCR. The tk gene was cloned and subsequently sequenced.. Conventional virological methods remained inconclusive. However, in situ hybridization and PCR rapidly confirmed the diagnosis of HSV-1 keratitis. The tk gene sequence revealed the presence of five variations previously described in two reference strains, but also a new point mutation at nucleotide position 431 which leads to an amino-acid change at position 144 that supported the hypothesis of a putatively altered functional form of the enzyme. Intravenous foscarnet treatment in an induction regimen was effective and cicatrization occurred within 3 weeks.. PCR and in situ hybridization are effective and powerful techniques when other virological procedures are non-contributive, particularly in immunocompromised patients previously treated with antiviral drugs. The new point mutation identified in the tk gene may be associated with resistance to acyclovir.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Amino Acid Sequence; Antiviral Agents; Base Sequence; Drug Resistance, Microbial; Female; Foscarnet; Herpesvirus 1, Human; Humans; In Situ Hybridization; Keratitis, Herpetic; Molecular Sequence Data; Point Mutation; Polymerase Chain Reaction; Thymidine Kinase; Treatment Outcome

The main goal of this study was to assess therapeutic strategies in HIV-infected patients with varicella-zoster virus infection.. This retrospective study conducted between 1989 and 1996 concerned 39 HIV-infected patients who had reached the AIDS stage and had at least one episode of varcella-zoster infection. Epidemiological, clinical and therapeutic data were recorded. Chi-squared test was used for comparisons.. A total of 78 episodes of varicella-zoster infection occurred including 39 primary episodes and 39 recurrences. Aciclovir (ACV) 200 mg per os was given in 27 cases as first intention therapy (mean dose 4000 mg/day for a mean 10 days), ACV 800 mg per os in 10 cases (mean dose 4000 mg per day for a mean 10 days), and intravenous ACV in 23 cases (mean dose 30 mg/kg/day for a mean 7 days). Foscarnet was used 5 times, 90-100 mg per day for 8 to 21 days. We did not observe any difference in efficacy between the three ACV formulations, probably because of the small number of patients in the series and the retrospective nature of the study. All of the failures of the oral treatments occurred in patients with CD4 counts below 100/mm3.. Aciclovir (800 mg) can be given in HIV-infected patients who develop non-complicated varicella-zoster virus infection. Intravenous aciclovir should be reserved for severe disseminated and/or neurological forms and for highly immunodepressed patients (for example those with a CD4 count below 200/mm3). These findings should be confirmed by prospective studies.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Chi-Square Distribution; Epidemiologic Methods; Herpesviridae Infections; Herpesvirus 3, Human; Humans; Male

Over a 2 year period, we identified five HIV-infected patients who presented with central nervous system infection caused by varicella-zoster virus, three with myelitits, and two with meningoencephalitis. All five patients were profoundly immunocompromised. Clinical presentation of these patients overlapped to a significant extent with diseases caused by other viruses, e.g. CMV. Indeed, in one case, a dual infection with CMV was diagnosed, but the respective role of each virus was ascertained by in situ hybridisation. At the time of CNS involvement, only one patient had active VZV cutaneous lesions, which were instrumental in diagnosing her condition. In contrast, PCR for VZV DNA in the CSF was helpful in making a diagnosis in the four other cases, one of which was confirmed by a post mortem. Of these five patients, two patients developed VZV disease while receiving oral acyclovir and had foscarnet treatment initiated when MRI demonstrated widespread lesions. They did not respond to antiviral therapy. The three other patients had intravenous acyclovir initiated at a time when no or limited parenchymal lesions were observed by MRI. Two of these three patients had VZV infection diagnosed solely on the basis of PCR: all three responded to treatment. Our data show that reactivation of VZV involving the central nervous system occurs frequently in the absence of cutaneous lesions. PCR of cerebrospinal fluid may help in making an early diagnosis which is probably a prerequisite for successful treatment of VZV infection of the CNS.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Central Nervous System Infections; Cytomegalovirus; DNA, Viral; Female; Foscarnet; Herpes Zoster; Herpesvirus 3, Human; HIV Infections; Humans; Immunocompromised Host; In Situ Hybridization; Male; Middle Aged; Polymerase Chain Reaction

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Chickenpox; Child; Female; HIV Seropositivity; Humans; Male; Pneumonia, Viral; Risk Factors; Seasons; Smoking

Herpes simplex virus (HSV) isolates were characterized from 8 AIDS patients in whom acyclovir and foscarnet therapy sequentially failed. The 6 postacyclovir (prefoscarnet) HSV isolates were resistant to acyclovir and susceptible to foscarnet. Of the 9 postfoscarnet isolates, 8 were foscarnet-resistant and acyclovir-susceptible, 1 was resistant to both drugs. Acyclovir- or foscarnet-resistant isolates retained susceptibility to cidofovir. The acyclovir-resistant isolates contained single-base substitutions or frameshift mutations in G or C homopolymer nucleotide repeats of the thymidine kinase gene. In contrast, the foscarnet-resistant strains contained single-base substitutions in conserved (II, III, or VI) or, more rarely, nonconserved (between I and VII) regions of the DNA polymerase (pol) gene. The single isolate exhibiting resistance to acyclovir and foscarnet contained mutations in both genes. In this study of clinical HSV isolates, DNA pol mutations conferring foscarnet resistance were not associated with decreased acyclovir or cidofovir susceptibility.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; DNA-Directed DNA Polymerase; Drug Resistance, Microbial; Foscarnet; Gene Products, pol; Herpes Simplex; Humans; Microbial Sensitivity Tests; Mutation; Simplexvirus; Thymidine Kinase; Treatment Failure

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: 2-Aminopurine; Acyclovir; Administration, Oral; AIDS-Related Opportunistic Infections; Antiviral Agents; Biological Availability; CD4 Lymphocyte Count; Drug Resistance, Microbial; Famciclovir; Herpes Zoster; Humans; Valacyclovir; Valine

This study aimed to describe a recently recognized and rare presentation of varicella zoster virus (VZV) retrobulbar optic neuritis preceding retinitis in patients with acquired immune deficiency syndrome and to identify factors that may relate to improved visual outcome.. Diagnosis, treatment, and clinical course are described for three eyes of two patients with this viral infection.. Patients had decreased vision, headache, and recent zoster dermatitis. Varicella zoster virus retrobulbar optic neuritis was diagnosed on the bases of clinical, laboratory, and electrophysiologic examination results. Profound vision loss and peripheral retinitis ensued despite intravenous antiviral treatment. Combination intravenous and intravitreous antiviral injections were administered with dramatic visual recovery.. Varicella zoster virus retrobulbar optic neuritis should be considered in immunocompromised patients with visual loss. Early diagnosis and aggressive combination therapy via systemic and intravitreous routes may enable return of useful vision.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cerebrospinal Fluid; Female; Foscarnet; Fundus Oculi; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Male; Meningitis, Viral; Optic Neuritis; Orbital Diseases; Retinitis; Skin Diseases, Viral; Visual Acuity

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

To assess a two-drug combination of antiviral therapy for the progressive outer retinal necrosis syndrome (PORN), given the current poor outcome with acyclovir alone.. A retrospective review was performed on six consecutive patients who were diagnosed with PORN and were treated with various combinations of intravenous or oral plus intravenous antiviral therapy. The relative efficacies of these modalities were compared.. Six eyes of six patients showed active retinitis at the time of presentation. Three patients had unilateral retinitis, and the remaining patients had necrotic, end-stage disease in their fellow eye. All the patients were treated with combination therapy, consisting of either ganciclovir and acyclovir (three patients), foscarnet and ganciclovir (two patients), or foscarnet and acyclovir (one patient). Standard induction doses were employed. During the combination therapy, all six eyes showed resolution of the retinitis, manifested by complete fading of the original retinal lesions and an absence of new lesion formation. At the final follow-up, the areas of prior active retinitis had resolved and remained quiescent. A mild recurrence developed in one eye when ganciclovir and foscarnet were both tapered to a single daily dose. This recurrence promptly resolved with reinduction (twice daily) dosing. Two patients maintained a visual acuity of 20/50 or better in their involved eye for the duration of follow-up (38 and 27 weeks, respectively). One patient maintained a visual acuity of 20/40 for 14 weeks. The remaining three patients had macula-off retinal detachments despite resolution of active retinitis. In addition, for the duration of follow-up, one of the three patients with unilateral disease had retinitis in the uninvolved eye; all three uninvolved fellow eyes maintained a visual acuity of 20/20. One patient had progressive optic atrophy.. Prolonged combination antiviral therapy for PORN may successfully arrest the progression of retinitis, maintain remission, and prevent involvement of the fellow eye. Furthermore, if aggressive therapy is begun early, good vision may be preserved.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus Retinitis; Disease Progression; Drug Therapy, Combination; Female; Follow-Up Studies; Foscarnet; Ganciclovir; Herpes Zoster Ophthalmicus; Humans; Male; Middle Aged; Recurrence; Retinal Necrosis Syndrome, Acute; Retrospective Studies; Treatment Outcome; 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

A man with acquired immunodeficiency syndrome (AIDS) developed zoster of the right arm which was resistant clinically to acyclovir. Varicella-zoster virus (VZV) was cultured from a skin biopsy performed at the beginning of acyclovir therapy (isolate 1) and after its failure (isolate 2). The emergence of acyclovir resistance during treatment was investigated by developing a simple and rapid drug sensitivity assay based on the plaque reduction reference method. This late-antigen synthesis reduction assay involved serial dilutions of cell-associated virus. The 50% inhibitory concentration (IC50) of acyclovir was 16 +/- 7.5 microM for the susceptible reference strain OKA, in agreement with published data. The acyclovir IC50 increased from 6.5 microM for isolate 1 to 100 microM for isolate 2. In comparison with the sequence of isolate 1, isolate 2 had a single mutation consisting of a C to T change at position 907 of the thymidine kinase gene, which changed a glutamine codon into a stop codon at position 303 of the thymidine kinase protein. These results show the emergence of acyclovir resistance through a single previously undescribed mutation in the thymidine kinase gene, and confirm the heterogeneity of mutations inducing acyclovir resistance.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Drug Resistance, Microbial; Genes, Viral; Herpes Zoster; Herpesvirus 3, Human; Humans; Male; Microbial Sensitivity Tests; Mutation; Polymerase Chain Reaction; Sequence Analysis, DNA; Thymidine Kinase; Viral Plaque Assay

Phenotypic and genotypic analyses were done on 30 acyclovir-resistant and 5 acyclovir-susceptible herpes simplex virus (HSV) isolates (22 HSV type 1 and 13 HSV type 2) recovered from 24 subjects. All isolates were susceptible to foscarnet. The phenotypes of the acyclovir-resistant HSV isolates were as follows: 17 were thymidine kinase (TK) deficient, 12 had decreased TK activity (produced low amounts of viral TK) or TK with altered substrate specificity, and 1 was undetermined. Sequencing analysis of the HSV TK gene revealed that 14 (46.7%) of 30 acyclovir-resistant isolates had an insertion or deletion of 1 or 2 nucleotides, especially in homopolymer runs of Gs, Cs, and rarely in As. On the other hand, 16 (53.3%) of 30 acyclovir-resistant isolates had point mutations in conserved or nonconserved regions of the TK gene. In conclusion, HSV can develop multiple strategies to exhibit acyclovir resistance, including, in about half of the cases, frameshift mutations in homopolymer nucleotide stretches of the TK gene.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Animals; Antiviral Agents; Cell Line; Chlorocebus aethiops; Drug Resistance, Microbial; Genotype; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Immunocompromised Host; Phenotype; Thymidine Kinase; Transplantation Immunology; Vero Cells

We report a case of bilateral acute retinal necrosis (ARN) following an acute optic neuromyelitis (AONM) in an immunodepressed patient (T CD4 lymphocyte count under 50/mm3) suffering from acquired immunodeficiency syndrome (AIDS). Despite the medical treatment the evolution led to blindness by bilateral total retinal detachment. The neuro-ophthalmological features occurred prior to the retinal manifestation, and the acute optic neuromyelitis occurred after a spreading zoster. The varicella-zoster virus (VZV) seemed to be involved because of recurring cutaneous zoster, spreading of this zoster just before the AONM, previous reports showing a link between VZV and AONM, and VZV and ARN. However, our patient had first an AONM responding well to corticosteroid therapy following one month later by an ARN leading to blindness despite the antiviral treatments received as soon as possible. There is a chronical viremia+ in immunodepressed patients with recurring and spreading zoster. The rupture of the hemato-encephalic barrier observed in AONM could facilitate the invasion of the eye by the virus, leading to an ARN. This hypothesis could explain the two complications due to the VZV, the AONM and the ARN, the first one is of dysimmunitary origin and the second one could probably result of a direct viral attack of the retina. This should incite to treat as soon as possible each retrobulbar optic neuritis in patients with AIDS, especially if past history of zoster.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Blood-Brain Barrier; Female; Herpes Zoster; Herpes Zoster Ophthalmicus; Humans; Neuromyelitis Optica; Retinal Necrosis Syndrome, Acute; Treatment Refusal

We retrospectively studied 18 consecutive cases of acyclovir-resistant zoster. All the patients had chronic skin lesions that failed to heal despite treatment with intravenous acyclovir (30 mg/[kg.d]) in 15 cases and oral acyclovir (4 g/d) in three cases for > 10 days. The mean CD4+ cell count was 20 x 10(6)/L. The mean number of previous zoster episodes was 1.53. Fifteen of the 16 patients evaluable for previous acyclovir treatment had received the drug. Thirteen patients were treated with intravenous foscarnet (200 mg/[kg.d]) for a mean of 17.8 days. Complete healing was observed in 10 (77%) of the 13 treated patients. Zoster relapsed after cessation of foscarnet therapy in five of the 10 responding patients. The median time to relapse was 110 days. Four patients died of varicella-zoster virus-associated visceral complications. These results show that acyclovir-resistant zoster has a poor prognosis but responds well to foscarnet therapy.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiviral Agents; Drug Resistance, Microbial; Foscarnet; Herpes Zoster; HIV Infections; Humans; Retrospective Studies; Treatment Outcome

Results of a study of high-dosage (8 g/day) valaciclovir and its relation to cytomegalovirus (CMV) disease show that 15 percent of subjects developed complications of CMV disease. Although some subjects developed CMV disease (12 percent) during valaciclovir treatment, the study reveals that there was an overall 33 percent reduction in the development of CMV in people using the drug. Gastrointestinal complaints occurred more often and earlier with subjects using valaciclovir rather than acyclovir. Also, signs of thrombotic microangiopathy occurred significantly more often in valaciclovir users versus acyclovir users. Reduced survival rates compared to acyclovir were noted, although this could be a result of too high of a dose of valaciclovir being administered.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Female; Humans; Male; Valacyclovir; Valine

A recent study done in Baltimore showed HSV-2 seroprevalence of 81% among 64 HIV-positive homosexual or bisexual men.. Our purpose was to examine HSV-2 as a risk factor for acquiring HIV infection, as well as to explore the possibility that acyclovir, an agent that inhibits the replication or infectivity in herpesviruses, might have a survival benefit to patients with HIV infection.. Studies were undertaken among HIV-positive patients to see if concomitant treatments including acyclovir offered a survival benefit.. A Multicenter AIDS Cohort Study held at four university-affiliated clinics and two landmark analyses demonstrated that acyclovir offered a significant survival advantage for HIV-positive patients. Another study had less conclusive results.. Enough evidence of a survival benefit in HIV-positive patients on long-term acyclovir therapy warrants consideration of long-term prophylactic therapy with suppressive doses of acyclovir as routine intervention for HIV-positive patients.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Bisexuality; Chemoprevention; Cohort Studies; Drug Resistance, Microbial; Herpes Genitalis; Herpes Simplex; HIV Infections; HIV Seropositivity; Homosexuality, Male; Humans; Male; Multicenter Studies as Topic; Risk Factors; Survival Rate; Virulence; Virus Replication

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: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cost-Benefit Analysis; Herpes Genitalis; Humans; Interferon-alpha; Male

To identify varicella-zoster virus (VZV) infections of the nervous system in patients infected with human immunodeficiency virus (HIV), polymerase chain reaction (PCR) analysis of cerebrospinal fluid (CSF) samples from 514 consecutive HIV-infected patients with neurological disease was performed to detect VZV DNA. VZV DNA was detected in CSF of 13 (2.5%) of 514 patients. Four of 13 patients had VZV encephalitis or meningoencephalomyelitis. These four patients received intravenous acyclovir therapy; CSF became negative for VZV DNA and clinical conditions improved for two, whereas CSF remained positive for VZV DNA and clinical conditions worsened until death for two. In nine of 13 patients, the neurological symptoms were likely caused by other simultaneous HIV-related complications in the central nervous system. After intravenous therapy with high doses of acyclovir or foscarnet, VZV was cleared from CSF in eight of nine patients. VZV DNA can be detected in CSF of HIV-infected patients in association with either manifestations of neurological VZV disease or subclinical reactivation of VZV infection. Antiviral treatment may be effective in suppressing VZV replication in the nervous system.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Central Nervous System Infections; DNA, Viral; Encephalitis, Viral; Encephalomyelitis; Herpes Zoster; Herpesvirus 3, Human; Humans; Meningoencephalitis; Polymerase Chain Reaction; Recurrence

Herpes simplex virus infection in immunocompromised individuals, including AIDS patients, is characterized by its tendency for atypical presentations and unusual locations, often resulting in delayed diagnosis and treatment. Three HIV-infected patients who developed prolonged cutaneous lesions of the fingers are presented. These lesions were unmodified by previous antibiotic treatment, and rapidly progressed to the complete destruction of nail structures in two patients. Viral culture confirmed the diagnosis of herpetic whitlow in all cases, and treatment with oral acyclovir resulted in complete recovery. Surgical treatment was not necessary.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Female; Fingers; Hand Dermatoses; Herpes Simplex; Humans; Male

To study the clinical, therapeutic, and evolutive features in 25 patients with the diagnosis of varicella pneumonia (VP) in the last 15 years.. The diagnosis was established by clinical and radiologic criteria in the course of varicella infection. The antecedents of smoking habit, pregnancy, and underlying disease were evaluated. Hypoxemia was defined as a pO2 < or = 65 mmHg with a FiO2 of 0.21.. Twenty-five patients (16 males and 9 women; mean age 31.5 years, range: 24-43 years) were included in the study. Ninety-two percent of patients were smokers of more than 20 cigarettes a day; five met criteria of simple chronic bronchitis, 3 were known carriers of human immunodeficiency virus (HIV) and one had a chronic liver disease caused by hepatitis C virus. In 16 patients (64%) there were no underlying diseases and none of the female patients was pregnant. Respiratory symptoms began from the first and seventh day after the skin rash, and the most common symptoms were cough (76%), dyspnea (48%), and chest pain (44%). In 22 patients an arterial gas determination was obtained and hypoxemia was documented in 8 patients (32%). Hypoxemia was greater and statistically significant in patients with underlying diseases (p < 0.01). Chest X-ray revealed an interstitial pattern predominantly at both bases. Intravenous acyclovir therapy was started in 19 patients (76%) with severe respiratory symptoms and/or underlying disease. Three patients (12%) were admitted to the Intensive Care Unit for mechanical ventilation. All patients had a favourable clinical course.. Adult patients with symptoms of VP had a favourable clinical course with intravenous acyclovir, and the presence of hypoxemia was more commonly observed when underlying diseases were also present.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Chickenpox; Female; HIV-1; Humans; Infusions, Intravenous; Male; Pneumonia, Viral; Pregnancy; Retrospective Studies; Smoking

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Disease Progression; Drug Therapy, Combination; Female; Follow-Up Studies; Ganciclovir; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Injections; Retinal Necrosis Syndrome, Acute; Vitreous Body

This paper presents a case of HIV-associated fulminating herpes zoster infection (HZI) that culminated in right mandibular necrosis and tooth exfoliation. The occurrence of such infection in immunosuppression and the impending clinical features are briefly reviewed and discussed.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Alveolar Bone Loss; Antiviral Agents; Herpes Zoster; Humans; Male; Mandibular Diseases; Osteonecrosis; Tooth Loss

To estimate the extent of aciclovir refractory herpes simplex virus (HSV) infection in HIV coinfected patients in the United Kingdom and survey clinicians on their approaches to its management.. Questionnaire survey of representative sample of one third of United Kingdom HIV physicians.. Use of antiviral therapies for genital HSV infections in HIV positive patients, reported frequency of aciclovir refractory HSV infection, its therapy, and access to antiviral susceptibility testing facilities.. 53 responses were obtained (response rate 61%), representing a sample size of 23% of United Kingdom HIV physicians. Use of non-standard antiviral regimens for HSV infections in HIV coinfected patients was widely practised, irrespective of the clinical characteristics of the HSV infection. Aciclovir refractory HSV infection has been observed by 37 (70%) respondents. Although foscarnet was the most frequently used therapy, used by 27/37 (73%) respondents, in only seven of these 27 (19%) was it a first line treatment for aciclovir refractory cases, frequently being used at a late stage in the clinical course. Antiviral susceptibility testing facilities were available to 46 (87%) clinicians. No respondents reported any evidence of transmission of aciclovir resistant strains.. HIV coinfection has a stronger influence on therapeutic choice than clinical immunosuppression or severity of herpetic infection. Aciclovir treatment failure is commoner than hitherto recognised. There is a need for wider awareness of use of foscarnet at an earlier stage in management of refractory HSV infection.

Topics: 2-Aminopurine; Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Drug Resistance, Microbial; Famciclovir; Foscarnet; Health Care Surveys; Herpes Genitalis; Humans; Immunocompromised Host; Recurrence

The frequency and severity of chronic herpes simplex virus (HSV-1) ulcerative infections were recorded in six HIV-infected children with severe immunodeficiency (mean CD4 + T lymphocytes/cmm = 39.4: range 8-66). The first episode of HSV infection consisted of vesicular-crusty lesions affecting the centro-facial cutis area. In five cases, relapses occurred 4 months later in the form of chronic ulcerative lesions that were always accompanied by a significant loss of tissue. Furthermore, three of the six children also showed perianal ulcerative lesions. Cytodiagnostic analysis revealed the typical cells in balloon degeneration; all of the children had HSV-1-positive vesicular fluid sample cultures. In our experience, chronic ulcerative HSV infection is relatively frequent in HIV-infected children (6.6%), and has unusual clinical manifestations with a good initial response to acyclovir treatment. Relapses are common and become increasingly worse and less responsive to treatment.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; CD4 Lymphocyte Count; Child; Child, Preschool; Chronic Disease; Cytodiagnosis; Fatal Outcome; Female; Herpes Simplex; Humans; Infant; Male; Recurrence

People with HIV are also frequently co-infected with herpes simplex viruses (HSV), although the interactions between the two are not fully understood. Evidence suggests that HSV is a risk factor for the transmission of HIV, is a common opportunistic pathogen in HIV-infected persons, and that HSV reactivation appears to regulate HIV replication. The clinical significance of these interactions is not well defined. Current information about the HSV-HIV interaction is reviewed, and future research projects are suggested. Advanced HIV infection has been associated with genital herpes, and unusually severe outbreaks of genital herpes and persistent herpetic ulcerations are an AIDS-defining diagnosis. Chronic anti-HSV therapy may be beneficial in some persons with HIV. Studies are being designed to address some of the outstanding issues in understanding the links between the two infections, and potential volunteers in the trials are invited to participate. Contact the University of Washington Virology Research Clinic for further information.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Disease Progression; DNA, Viral; Female; Herpes Genitalis; Herpesvirus 2, Human; HIV Infections; Humans; Male; Polymerase Chain Reaction; Up-Regulation; Virus Shedding

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

Effective diagnosis and treatment of cytomegalovirus infection of the nervous system in AIDS patients has been limited by a lack of sensitive diagnostic measures. Retrospective series suggest a poor prognosis for cytomegalovirus encephalitis with rapid mortality. Polymerase chain reaction amplification of cytomegalovirus DNA allows detection in CSF that appears specific for CNS infection. In this series of seven patients with CNS cytomegalovirus infection in AIDS, four patients responded to therapy. Serial determinations of cytomegalovirus DNA in CSF in five patients revealed persistent detection in two treatment failures and absence of detection in three responders on subsequent CSF samples. A prospective trial to determine optimal therapy and to confirm the utility of cytomegalovirus DNA in CSF as a marker of the course of cytomegalovirus infection in the CNS is warranted and should consider prior therapy for cytomegalovirus, prior opportunistic infections, and leukoencephalopathy as potential prognostic variables.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Base Sequence; Cerebrospinal Fluid; Cytomegalovirus; Cytomegalovirus Infections; DNA Primers; Encephalitis; Foscarnet; Ganciclovir; Genes, Immediate-Early; HIV Seropositivity; Humans; Male; Meningitis; Molecular Sequence Data; Polymerase Chain Reaction; Prognosis; Sensitivity and Specificity; Spinal Cord Diseases

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Diagnosis, Differential; Herpes Zoster Oticus; Humans

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Retinitis; Drug Resistance, Microbial; Drug Therapy, Combination; Exudates and Transudates; Foscarnet; Fundus Oculi; Ganciclovir; Humans; Infusions, Intravenous; Male; Recurrence; Retinal Detachment; Visual Acuity

Persistent mucocutaneous ulcers in AIDS represent a variety of disease entities. The purpose of this study was to characterize clinicopathologic features of persistent oral ulcers associated with cytomegalovirus and herpes simplex virus in AIDS. Forty-seven persons infected with HIV with persistent ulcers (mean, 2.4 ulcers/person) were included in this study. A biopsy specimen from a representative ulcer was taken from each patient. Hematoxylin-eosin, periodic acid-Schiff, cytomegalovirus, and herpes simplex virus immunocytochemical stains were performed on tissue sections. The most common sites of involvement were the buccal/labial mucosa (27%), tongue (25%), and gingiva (18%). Mean ulcer size was 1.8 cm with a mean duration of 5.6 weeks. The ulcerogenic viral agents were cytomegalovirus alone in 53% of cases, cytomegalovirus and herpes simplex virus coinfection in 28% of cases, and herpes simplex virus alone in 19% of cases. Treatment response to ganciclovir with or without topical steroids resulted in lesion resolution in the cytomegalovirus and cytomegalovirus/herpes simplex virus groups; however, recurrence/resistance was relatively high (23%). Herpes simplex virus/cytomegalovirus ulcers responded to oral acyclovir in combination with systemic ganciclovir. Increasing the oral acyclovir dosage resulted in resolution of herpes simplex virus-only ulcers in all but one case. Cytomegalovirus and herpes simplex virus are associated with persistent mucocutaneous ulcers in AIDS. These lesions responded to systemic antiviral therapy but are difficult to differentiate from other ulcerogenic diseases such as aphthous major, necrotizing stomatitis, and ulcerations not otherwise specified without biopsy and histopathologic examination.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cytomegalovirus Infections; Cytopathogenic Effect, Viral; Diagnosis, Differential; Female; Ganciclovir; Humans; Male; Middle Aged; Mouth Diseases; Recurrence; Stomatitis, Herpetic; Ulcer

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Arabinofuranosyluracil; Chickenpox; Drug Resistance, Microbial; Female; Ganciclovir; Herpesvirus 3, Human; Humans; Retinal Necrosis Syndrome, Acute

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

Only a few cases of varicella-zoster virus (VZV) myelitis have been described, and nearly all have been diagnosed post-mortem. There have been no reports in the literature of successful treatment of VZV myelitis with antiviral medications. We report on two patients with AIDS who had acute severe myelitis accompanied by herpes zoster. The presence of VZV DNA in cerebrospinal fluid (CSF) was documented by the polymerase chain reaction (PCR) technique. Early treatment with acyclovir was followed by a slow but complete recovery after a phase of initial aggravation. After a follow-up of > 1 year, the two patients remained asymptomatic. We conclude that (1) VZV should be considered a curable cause of myelitis in patients with AIDS, (2) PCR assay of CSF will assist in early diagnosis, and (3) early treatment with acyclovir should aid in recovery.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; DNA, Viral; Female; Follow-Up Studies; Herpesviridae Infections; Herpesvirus 3, Human; Humans; Male; Myelitis

Two patients with AIDS developed protracted infection due to autoinoculation of herpes simplex virus in the great toe and the external ear, respectively, both unusual areas for inoculation. The appearances of the lesions were also unusual; severe hyperkeratosis was noted in both cases and a mass lesion in the external ear in one case. Both patients' conditions responded to acyclovir, although one patient required amputation of a digit due to intractable pain. In each case, the diagnosis was delayed despite the presence of mucocutaneous lesions, resulting in inappropriate treatment and prolonged discomfort. Inoculation disease due to herpes simplex virus should be suspected in patients with AIDS who have unusual skin lesions, particularly if oral and/or perianal lesions are also present.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Ear; Fatal Outcome; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Male; Toes; Tomography Scanners, X-Ray Computed

A 39-year-old HIV-infected man had manifested a typical varicella successfully treated with intravenous acyclovir. Despite oral acyclovir, he developed 10 days later a widespread eruption of pinpoint-sized erythematous papular lesions. Histologic examination and viral culture showed a persistent varicella-zoster virus (VZV) infection. Intravenous acyclovir and foscarnet were both efficient. However, each withdrawal of intravenously administered treatment resulted in a rapid relapse. Among the atypical forms of chronic varicella, this eruption appears to be unique. As in our case, chronic VZV infection appears often to be a difficult therapeutic challenge.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Chickenpox; Chronic Disease; Fatal Outcome; Foscarnet; Humans; Male; Recurrence

Four HIV-positive patients with herpes simplex virus and cytomegalovirus coinfected oral ulcers are presented. All patients had persistent oral pain associated with nonhealing mucosal ulcers. Lesions occurred on the palate, retromolar pad, tongue, and lip, and the clinical appearance of the ulcers was nonspecific. Histologic and immunohistochemical stains showed herpes simples virus alterations in keratinocyte nuclei and cytomegalovirus alterations in mesenchymal/endothelial cell nuclei and cytoplasm. Lesions in one patient responded to ganciclovir therapy. One patient improved with acyclovir, and another healed normally after excisional biopsy. Each virus alone has been described as causing oral ulcerations; their appearance together in the same lesion would suggest a synergistic relationship.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cell Nucleus; Cytomegalovirus; Cytomegalovirus Infections; Cytoplasm; Endothelium, Vascular; Follow-Up Studies; Ganciclovir; Gingival Diseases; HIV Seropositivity; Humans; Immunohistochemistry; Keratinocytes; Lip Diseases; Male; Mesoderm; Middle Aged; Mouth Diseases; Palate; Simplexvirus; Stomatitis, Herpetic; Tongue Diseases; Ulcer

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Drug Resistance; Herpesviridae Infections; Humans; Male; Simplexvirus; Skin; Trifluridine; Tumor Virus Infections

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Anus Diseases; Herpes Simplex; Humans; Injections, Intramuscular; Interferon alpha-2; Interferon-alpha; Male; Recombinant Proteins; Ulcer

To describe the clinical course of varicella-zoster optic neuropathy preceding acute retinal necrosis in patients with acquired immunodeficiency syndrome.. Case series.. Two tertiary care centers in San Diego, Calif, and London, England.. Three human immunodeficiency virus-positive men with previous cutaneous zoster infection, optic neuropathy, and necrotizing retinitis.. All patients had an episode of zoster dermatitis treated with acyclovir. Visual loss consistent with an optic neuropathy ensued, followed by typical herpetic retinitis. The cause of visual loss was not suspected to be varicella-zoster until after the retinitis occurred. Despite aggressive medical treatment, 4 of 6 eyes progressed to retinal detachment.. Varicella-zoster may cause an optic neuropathy in patients with acquired immunodeficiency syndrome, especially in those with previous shingles. A high index of suspicion is necessary to establish the diagnosis and begin early antizoster treatment.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antigens, Viral; Antiviral Agents; Dermatitis; Fluorescein Angiography; Fundus Oculi; Herpes Zoster; Herpes Zoster Ophthalmicus; Herpesvirus 3, Human; Humans; Immunohistochemistry; Male; Middle Aged; Optic Nerve Diseases; Retina; Retinal Necrosis Syndrome, Acute; Skin Diseases, Viral; Visual Acuity; Vitreous Body

A patient with AIDS who developed the clinical picture of bilateral progressive outer retinal necrosis (PORN) in combination with varicella zoster encephalitis is described. The picture developed more than 2 years after an episode of ophthalmic zoster infection, and following intermittent exposure to oral acyclovir because of recurrent episodes of cutaneous herpes simplex infection.. Aqueous humour, obtained by paracentesis of the anterior chamber, was analysed using immunofluorescence and polymerase chain reaction (PCR). Postmortem analysis of eye and brain tissue was performed by using conventional techniques and in situ hybridisation.. While conventional techniques all failed to detect a causative agent, analysis of the aqueous humour using PCR, and histological examination of necropsy specimens from eyes and brain using in situ hybridisation were conclusive for the diagnosis varicella zoster virus (VZV) infection.. This case documents the presumed association of PORN and VZV encephalitis in a severely immunocompromised AIDS patient.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Encephalitis, Viral; Herpes Simplex; Herpes Zoster; Humans; In Situ Hybridization; Male; Necrosis; Polymerase Chain Reaction; Retinal Diseases

Two cases of varicella-zoster virus infection that were clinically and pathologically verrucous are reported. Although this phenomenon has previously been described in the dermatology literature, it has not, to our knowledge, been described in the pathology literature. It is important that pathologists are aware of these uncommon but histologically distinctive lesions.. The patients were seen and treated at the Departments of Dermatology of the University of Texas Health Science Center at San Antonio and Brackenridge Hospital in Austin, Tex. All information was derived from the medical records and from the attending physicians.. Verrucous lesions of herpes (varicella) zoster virus infection are rare, but they do occur in patients with the acquired immunodeficiency syndrome. Clinically, the lesions studied resembled ordinary papillomavirus-induced verrucae. Histologically, there was verrucoid epidermal hyperplasia and, unlike ordinary lesions of herpes (varicella) zoster, very little inflammation of the dermis. Diagnostic multinucleated keratinocytes with herpesvirus cytopathic changes were present within the stratum corneum.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Chickenpox; Cytopathogenic Effect, Viral; Humans; Keratinocytes; Male

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

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Bias; Female; Follow-Up Studies; Foscarnet; Ganciclovir; HIV Seropositivity; Humans; Information Systems; Male; Proportional Hazards Models; Risk Factors; Sarcoma, Kaposi

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Herpes Zoster; Humans; Male; Pneumonia, Viral

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

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Drug Resistance, Microbial; Female; Foscarnet; Herpes Zoster; Herpesvirus 3, Human; Humans

We describe a 28-year-old HIV-infected woman with AIDS, defined by cerebral toxoplasmosis and a CD4-count of less than 10 x 10(6) cells/I, who, after several eruptions of genital herpes and typical dermatomal herpes zoster, all successfully treated with acyclovir, developed chronic cutaneous ulcerating lesions on a finger and on the tibia. The lesions were found to contain varicella zoster virus antigen but repeated treatment courses with acyclovir were unsuccessful. After a course of intravenous foscarnet the lesions resolved. They recurred after discontinuation of foscarnet but finally responded to a second course of treatment.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Chronic Disease; Drug Resistance, Microbial; Female; Foscarnet; Herpes Zoster; Herpesvirus 3, Human; Humans; Skin Ulcer

The Second Human Retroviruses Conference covered many topics, including statistics on the viruses' prevalence in American society and some survey results on sexual behavior. Conference meetings were dominated by discussions on protease inhibitors and current clinical trial data on two inhibitors in particular, 3TC and ZDV. Evidence of a new herpes virus causing Kaposi's sarcoma (KS), and research on anti-KS agents, were discussed, including assessments concerning the struggle between the virus and the immune system, and arguments about using immune-based therapies versus attacking the virus directly. Of particular interest concerning immune-based therapy was the National Institute of Allergy and Infectious Diseases' (NIAID) interleukin-2 trial which is showing impressive results in affecting CD4+ counts, if CD4+ counts are not too low initially. Antiretroviral information centered on two investigations surrounding Parke-Davis' PD121871 and PD144975, which seem to prevent activation of latently-infected cells, and return activated cells to a quiescent state. Other conference topics covered acyclovir survival levels, the new therapies and renewed concerns about cytomegalovirus, planning an overall prophylactic strategy, the slow progress in developing a vaccine, and whether low-dose chemotherapy for lymphoma was as good as the standard dose.

Topics: Acyclovir; AIDS Vaccines; AIDS-Related Opportunistic Infections; Antineoplastic Agents; Antiviral Agents; CD4 Lymphocyte Count; Cytomegalovirus Retinitis; Herpesviridae; HIV Infections; Humans; Interleukin-2; Lamivudine; Lymphoma, Non-Hodgkin; Retroviridae; Sarcoma, Kaposi; Zalcitabine; 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

As more drugs are approved for the prevention of opportunistic infections, concerns regarding the benefits and potential risks of these therapies are arising. A synopsis of the data for prophylaxis against opportunistic infections is provided for the following: Pneumocystis carinii pneumonia, fungal infections, Mycobacterium avium complex, cytomegalovirus infections, and toxoplasmosis. General precautions in using preventive medications for people with fewer than 100 CD4 plus cells are highlighted.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Clarithromycin; Clindamycin; Clinical Trials as Topic; Clotrimazole; Cytomegalovirus Infections; Dapsone; Fluconazole; Ganciclovir; Humans; Itraconazole; Leucovorin; Mycobacterium avium-intracellulare Infection; Mycoses; Pentamidine; Pneumonia, Pneumocystis; Pyrimethamine; Rifabutin; Toxoplasmosis; Trimethoprim, Sulfamethoxazole Drug Combination; Valacyclovir; Valine

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: Acyclovir; AIDS Dementia Complex; AIDS-Related Opportunistic Infections; Cytomegalovirus Infections; Encephalitis, Viral; Ganciclovir; Herpes Simplex; HIV-1; Humans

Neurologic complications are common in patients with AIDS. Herpes zoster is a common early manifestation of HIV infection, but there have been few reports of encephalitic complications and nearly all have been postmortem. We report four cases of varicella zoster virus (VZV) meningoencephalitis diagnosed and treated antemortem, and briefly review the relevant literature.. Mount Zion Medical Center, San Francisco, California, USA.. Four HIV-positive male patients with antibodies to VZV in their cerebrospinal fluid.. Treatment with intravenous acyclovir (three cases) and intravenous ganciclovir (one case), which resulted in resolution of all symptoms except blindness in one patient.. Antibodies to VZV in the cerebrospinal fluid of HIV-positive individuals may allow early diagnosis and lifesaving treatment of VZV meningoencephalitis.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antibodies, Viral; Ganciclovir; Herpes Zoster; Herpesvirus 3, Human; HIV Seropositivity; Humans; Male; Meningoencephalitis; Middle Aged

Phenotypic and genotypic analyses were done on 17 varicella-zoster virus (VZV) isolates recovered from 10 persons with AIDS (mean CD4 cell count, 16.4/mm3) who had chronic VZV lesions. Eleven acyclovir-resistant isolates were recovered from 10 patients after a mean of 20.1 weeks of therapy. Six susceptible isolates were recovered before acyclovir treatment (n = 1), early during therapy (n = 4; mean time, 4.2 weeks), or after discontinuation of acyclovir (n = 1). Acyclovir-resistant VZV isolates were deficient in thymidine kinase (TK) or induced a TK with altered substrate specificity; all isolates were susceptible to foscarnet. Ten of 11 acyclovir-resistant mutants contained tk gene mutations, including single nucleotide substitutions in highly conserved binding sites (n = 2) as well as nucleotide deletions (n = 4) and insertions (n = 4). These findings suggest that multiple, nonuniform mutations within the tk gene are associated with acyclovir-resistant VZV phenotypes.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Amino Acid Sequence; Base Sequence; Cells, Cultured; DNA, Viral; Drug Resistance, Microbial; Genotype; Herpes Zoster; Herpesvirus 3, Human; Humans; Molecular Sequence Data; Phenotype; Polymerase Chain Reaction; Thymidine Kinase

The acyclic nucleoside phosphonate (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) was used topically for the treatment of persistent mucocutaneous infections in two cases. One patient with AIDS suffered from a perineal lesion due to infection with herpes simplex virus type 2 (HSV-2) and did not respond to acyclovir and was intolerant of foscarnet. A bone marrow transplant recipient developed orofacial lesions due to infection with herpes simplex virus type 1 (HSV-1) that failed to respond to therapy with both acyclovir and foscarnet. After topical application of HPMPC, the HSV-2 lesions completely resolved. However, the lesions recurred 3 weeks later, and, upon subsequent treatment with HPMPC, regressed. On recurrence, the virus was found to be sensitive to acyclovir, which the patient was given. Again HSV-2, which was resistant to acyclovir, emerged; similar observations were made after another cycle of HPMPC therapy. The HSV-1 isolates were resistant to acyclovir and foscarnet. Following local HPMPC treatment, the lesions regressed, but after 1 week, a second course of topical HPMPC therapy had to be instituted for recurrent infection. The lesions again regressed, and as the recurrent virus was sensitive to acyclovir, the patient was successfully treated with the drug. The results of this study point to the potential usefulness of topical HPMPC in the treatment of immunocompromised patients with HSV-related mucocutaneous infections that are refractory to therapy with acyclovir and/or foscarnet.

Topics: Acyclovir; Administration, Topical; Adult; AIDS-Related Opportunistic Infections; Antiviral Agents; Cidofovir; Cytosine; DNA Restriction Enzymes; DNA, Viral; Drug Resistance, Microbial; Foscarnet; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Opportunistic Infections; Organophosphonates; Organophosphorus Compounds; Skin Diseases, Viral; Thymidine Kinase

The various clinical presentations of infectious esophagitis have been discussed. The physician approach to patients with suspected infectious esophagitis is based on whether the patient has an underlying immune problem. Symptomatic patients with thrush and AIDS should be empirically treated but most other patients should be referred to endoscopy. Considering the AIDS epidemic, any patient without known immune deficiency who is diagnosed with infectious esophagitis should be screened for an immunodeficiency disorder.

Topics: Acyclovir; Adult; AIDS Serodiagnosis; AIDS-Related Opportunistic Infections; Esophagitis; Herpes Simplex; Herpesvirus 1, Human; HIV Seronegativity; Humans; Male

(S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine (HPMPC) is a nucleotide analogue with potent in vitro and in vivo activity against a broad range of herpesviruses, including acyclovir-resistant herpes simplex virus (HSV). A patient with severe acyclovir-resistant perineal HSV infection received intravenous HPMPC at 5 mg/kg/week, with concomitant oral probenecid and prehydration, and had 95% healing after four infusions. The patient developed a hypersensitivity reaction to probenecid and discontinued HPMPC after the fourth infusion. Recurrence of the perineal lesions 2 weeks later prompted initiation of an oral desensitization program to probenecid and enabled the patient to resume therapy. The lesions again responded to infusions of HPMPC, but the drug was discontinued before complete healing because of transient nephrotoxicity (proteinuria, 2+; creatinine, 1.7 mg/dL). HPMPC is a potent antiviral agent that holds promise as a potential treatment for acyclovir-resistant HSV infection.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Antiviral Agents; Cidofovir; Cytosine; Drug Resistance, Microbial; Herpes Simplex; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Organophosphonates; Organophosphorus Compounds; Simplexvirus

Chronic laryngitis in patients with acquired immunodeficiency syndrome may be due to infections or tumors, such as Kaposi's sarcoma and non-Hodgkin's lymphoma. We present what we believe to be the first proven case of herpes simplex virus chronic laryngitis in a man positive for human immunodeficiency virus. Direct laryngoscopy showed leukoplakic lesions on both vocal cords. Biopsy of the lesions showed squamous epithelial cells with the characteristic features of herpes simplex virus, which was confirmed by immunohistochemical stains. We discuss the differential diagnosis of chronic laryngitis in a human immunodeficiency virus infection. Herpes simplex viral infection of the vocal cords should be considered in patients with acquired immunodeficiency syndrome presenting with chronic hoarseness and leukoplakic lesions on direct laryngoscopy, especially with no evidence of Kaposi's sarcoma, tumor, or cytomegaloviral or fungal infection elsewhere. Treatment should be acyclovir, except in the face of acyclovir resistance.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Biopsy; Chronic Disease; Diagnosis, Differential; Herpes Simplex; Humans; Laryngitis; Laryngoscopy; Male; Middle Aged; Vocal Cords

A child infected with HIV who developed chronic varicella zoster virus infection resistant to acyclovir is presented. The clinical course of the infection, treatment, virological investigations, and relationship of the infection to the child's immunodeficient state are discussed.

Topics: Acyclovir; AIDS-Related Opportunistic Infections; Chickenpox; Chronic Disease; Drug Resistance, Microbial; Fatal Outcome; Follow-Up Studies; Herpes Zoster; Herpesvirus 3, Human; Humans; Infant; Male; Skin

Cytomegalovirus retinopathy is the most frequent opportunistic infection of the eye in patients with acquired immunodeficiency syndrome (AIDS). We studied 71 patients with cytomegalovirus retinopathy (n = 69) or acute retinal necrosis (n = 2) with respect to the frequency and management of retinal detachment. Retinal detachment was seen in 14 patients (relative frequency, 19.7%). In 2 patients, the retinal detachment was bilateral. In 5 patients, pars plana vitrectomy and silicone-oil tamponade was performed, and in 1 of these patients scleral buckling was applied before vitrectomy. In 3 other patients scleral buckling was performed, and 1 of these individuals had sulfur-hexafluoride injection. In 8 eyes (6 patients), retinal detachment occurred in eyes with completely burned-out retinopathy without relevant function, and no surgical treatment was performed. Long-term retinal reattachment was seen in all 5 patients undergoing pars plana vitrectomy with silicone-oil tamponade. Visual acuity was preserved until the last follow-up in 4 of these 5 patients. In the patients undergoing a buckling procedure alone, no anatomic or functional success was observed. During vitrectomy, reduced retinal vascular perfusion and blood-flow sludging was observed in 2 patients. As the duration of survival of patients with AIDS and cytomegalovirus retinopathy or acute retinal necrosis is increasing, more cases of retinal detachment will be observed. Overall, 5% of patients with AIDS are expected to develop retinal detachment. In conclusion, treatment of cytomegalovirus-associated retinal detachment by pars plana vitrectomy with silicone-oil tamponade seems to be successful and safe and may maintain the patient's quality of life.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Cytomegalovirus Retinitis; Follow-Up Studies; Foscarnet; Ganciclovir; Humans; Incidence; Male; Retinal Detachment; Retinal Necrosis Syndrome, Acute; Visual Acuity

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

Six human immunodeficiency virus-infected patients had clinical lesions of herpes simplex virus (HSV) type 2 that showed in vitro resistance to foscarnet. In each patient, lesions were unresponsive to foscarnet therapy or developed during daily suppressive foscarnet. Five patients had a history of intermittent or chronic foscarnet use for the management of acyclovir-resistant HSV infection, and 1 was receiving daily foscarnet for suppression of cytomegalovirus retinitis. Seven of 10 foscarnet-resistant isolates from 6 patients were susceptible to acyclovir in vitro, and 1 was of borderline susceptibility. In 3 patients, the administration of acyclovir, either alone or in combination with foscarnet, resulted in healing. Clinically significant resistance to foscarnet may occur in immunosuppressed patients with prior foscarnet exposure. Addition or substitution of acyclovir to foscarnet therapy may be a useful strategy for patients in whom foscarnet resistance is suspected, pending the results of in vitro susceptibility testing.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Drug Resistance, Microbial; Drug Therapy, Combination; Foscarnet; Ganciclovir; Herpes Genitalis; Herpes Labialis; Herpesvirus 2, Human; Humans; Microbial Sensitivity Tests; Vidarabine

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Cerebrovascular Disorders; Female; Herpes Zoster; Humans; Male; Middle Aged; Necrosis; Retinitis; Vasculitis

We report a case of disseminated herpes zoster in a pregnant patient positive for the human immunodeficiency virus (HIV). Disseminated zoster was the first manifestation of HIV infection in this patient. In HIV-positive patients, zoster may be complicated by cutaneous dissemination, visceral involvement, and death. Intravenous acyclovir may prevent serious sequelae in both mother and fetus.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Female; Herpes Zoster; Humans; Pregnancy; Pregnancy Complications, Infectious

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Drug Resistance, Microbial; Female; Foscarnet; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; HIV Infections; Humans; Male; Middle Aged; Stomatitis, Herpetic; Vidarabine

Five patients with acquired immunodeficiency syndrome (AIDS) and presumed varicella-zoster virus retinopathy had recurrence of retinopathy after stabilization with initial intravenous antiviral therapy. Recurrences were recognized as increased retinal opacification at the borders of preexisting lesions or as new lesions. In four of the five patients, recurrences were temporally associated with a reduction in the amount of antiviral medication being received. Changes included switch from intravenous to oral acyclovir (two patients), taper of oral acyclovir (one patient), and discontinuation of medications (one patient). In four patients disease was initially unilateral; in three of these four, disease subsequently developed in the previously unaffected fellow eye at the time of recurrence. The median time from stabilization of disease to recurrence was 51 days (range, 14 to 90 days). In contrast to the management of varicella-zoster virus retinopathy in immunocompetent patients and varicella-zoster virus lesions of the skin, varicella-zoster virus retinopathy in patients with AIDS appears to require chronic suppressive antiviral therapy to prevent recurrences. In this respect it is similar to other opportunistic retinal infections in patients with AIDS. The best drugs and optimal treatment regimens for maintenance antiviral therapy remain unknown.

Topics: Acyclovir; Administration, Oral; Adult; AIDS-Related Opportunistic Infections; Foscarnet; Fundus Oculi; Herpes Zoster Ophthalmicus; Humans; Injections, Intravenous; Male; Recurrence; Retinal Diseases

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Herpes Simplex; Humans; Male; Pneumonia, Viral

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

Recurrent oral herpes simplex virus lesions are common in both immunocompetent and immunocompromised persons. In contrast, cytomegalovirus-associated intraoral lesions are rarely seen, even in the immunocompromised host. We report a case of concurrent oral herpes simplex virus and cytomegalovirus infection, appearing as an ulcerative lesion of the labial mucosa in a patient with acquired immunodeficiency syndrome. Herpes simplex virus type 1 was shown to be present in the lesion by culture tests, histopathologic examination, immunohistochemistry findings and a direct immunofluorescence assay, and cytomegalovirus by histopathologic examination and immunohistochemistry findings. We deduce that the lesion was due to concurrent herpes simplex virus-1 and cytomegalovirus infection. The patient responded well to 2 weeks of treatment with a high dose of acyclovir.

Topics: Acyclovir; Adult; AIDS-Related Opportunistic Infections; Antibodies, Monoclonal; Cytomegalovirus; Cytomegalovirus Infections; Humans; Lip Diseases; Male; Mouth Diseases; Mouth Mucosa; Simplexvirus; Stomatitis, Aphthous; Stomatitis, Herpetic; Superinfection