acyclovir and Opportunistic-Infections

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients. Pre-emptive treatment of patients with CMV viraemia using antiviral agents has been suggested as an alternative to routine prophylaxis to prevent CMV disease. This is an update of a Cochrane review first published in 2005.. This review was conducted to evaluate the efficacy of pre-emptive treatment with antiviral medications in preventing symptomatic CMV disease.. For this update, we searched the Cochrane Renal Group's Specialised Register (to 16 January 2013) through contact with the Trials' Search Co-ordinator using search terms relevant to this review.. We included randomised controlled trials (RCTs) of pre-emptive treatment compared with placebo, no specific treatment or with antiviral prophylaxis in solid organ transplant recipients.. Four authors assessed the quality and extracted all data. Analyses used a random-effects model and results were expressed as risk ratio (RR) and 95% confidence intervals (CI).. We identified 15 eligible studies (1098 participants). Of these, six investigated pre-emptive treatment versus placebo or treatment of CMV when disease occurred (standard care), eight looked at pre-emptive treatment versus antiviral prophylaxis, and one reported on oral versus intravenous pre-emptive treatment.Assessment of risk of bias identified that the processes reported for sequence generation and allocation concealment were at low risk of bias in only five and three studies, respectively. All studies were considered to be at low risk of attrition bias, and seven studies were considered to be at low risk of bias for selective reporting. Only one study reported adequate blinding of participants and personnel; no study reported blinding of outcome assessment.Compared with placebo or standard care, pre-emptive treatment significantly reduced the risk of CMV disease (6 studies, 288 participants: RR 0.29, 95% CI 0.11 to 0.80) but not acute rejection (3 studies, 185 participants: RR 1.21, 95% CI 0.69 to 2.12) or all-cause mortality (3 studies, 176 participants: RR 1.23, 95% CI 0.35 to 4.30). Comparative studies of pre-emptive therapy versus prophylaxis showed no significant differences in preventing CMV disease between pre-emptive and prophylactic therapy (7 studies, 753 participants: RR 1.00, 95% CI 0.36 to 2.74) but there was significant heterogeneity (I² = 63%). Leucopenia was significantly less common with pre-emptive therapy compared with prophylaxis (6 studies, 729 participants: RR 0.42, 95% CI 0.20 to 0.90). Other adverse effects did not differ significantly or were not reported. There were no significant differences in the risks of all-cause mortality, graft loss, acute rejection and infections other than CMV.. Few RCTs have evaluated the effects of pre-emptive therapy to prevent CMV disease. Pre-emptive therapy is effective compared with placebo or standard care. Despite the inclusion of five additional studies in this update, the efficacy of pre-emptive therapy compared with prophylaxis to prevent CMV disease remains unclear due to significant heterogeneity between studies. Additional head-to-head studies are required to determine the relative benefits and harms of pre-emptive therapy and prophylaxis to prevent CMV disease in solid organ transplant recipients.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Immunocompromised Host; Opportunistic Infections; Organ Transplantation; Randomized Controlled Trials as Topic; Viremia

Opportunistic viral infections are a well-recognized complication of anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD). Cases of severe or atypical varicella zoster virus infection, both primary and latent reactivation, have been described in association with immunosuppression of Crohn's disease (CD) patients. However, central nervous system varicella zoster virus infections have been rarely described, and there are no previous reports of varicella zoster virus meningitis associated with anti-TNF therapy among the CD population. Here, we present the case of a 40-year-old male with severe ileocecal-CD who developed a reactivation of dermatomal herpes zoster after treatment with prednisone and adalimumab. The reactivation presented as debilitating varicella zoster virus meningitis, which was not completely resolved despite aggressive antiviral therapy with prolonged intravenous acyclovir and subsequent oral valacyclovir. This is the first reported case of opportunistic central nervous system varicella zoster infection complicating anti-TNF therapy in the CD population. This paper also reviews the literature on varicella zoster virus infections of immunosuppressed IBD patients and the importance of vaccination prior to initiation of anti-TNF therapy.

Topics: Acyclovir; Adalimumab; Adrenal Cortex Hormones; Adult; Antibodies, Monoclonal, Humanized; Antiviral Agents; Crohn Disease; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Meningitis, Viral; Opportunistic Infections; Prednisone; Treatment Outcome; Tumor Necrosis Factor-alpha; Valacyclovir; Valine; Virus Activation

Topics: Acyclovir; Aged; Antiviral Agents; Cross-Sectional Studies; Diagnosis, Differential; DNA, Viral; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Male; Middle Aged; Neuralgia, Postherpetic; Neurologic Examination; Opportunistic Infections; Pain Measurement; Polymerase Chain Reaction; Prognosis; Quality of Life; Risk Factors

Prevention of cytomegalovirus (CMV) infection is an important part of clinical care provided to patients after solid organ transplantation. While the optimal preventive strategy has not been defined, most centers rely on universal prophylaxis or pre-emptive therapy. This article comments on recent studies designed to identify strategies that effectively reduce the incidence of late-onset CMV disease as the main problem associated with prophylaxis, and on recent data regarding the development of CMV-specific immunity depending on the CMV-preventive regimen used. Despite an apparent trend to prefer prophylaxis in clinical practice, this approach does not seem to be based on robust evidence.

Topics: Acyclovir; Antiviral Agents; Clinical Protocols; Cytomegalovirus Infections; Ganciclovir; Humans; Immunosuppressive Agents; Opportunistic Infections; Organ Transplantation; Randomized Controlled Trials as Topic; Valacyclovir; Valganciclovir; Valine

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in solid organ transplant recipients. Pre-emptive treatment with antiviral agents of patients with CMV viraemia has been widely adopted as an alternative to routine prophylaxis to prevent CMV disease.. This review was conducted to evaluate the efficacy of pre-emptive treatment in preventing symptomatic CMV disease.. The Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library Issue 2, 2005), MEDLINE (1966 to February 2005), EMBASE (1980 to February 2005) and reference lists and conference proceedings were searched.. We included randomised controlled trials (RCTs) of pre-emptive treatment versus placebo, no treatment or antiviral prophylaxis in solid organ transplant recipients.. Two authors assessed the quality and extracted all data. Analysis was with a random-effects model and results expressed as relative risk (RR) and 95% confidence intervals (CI).. Ten eligible trials (476 patients) were identified, six of pre-emptive treatment versus placebo or treatment of CMV when disease occurred (standard care), three of pre-emptive treatment versus antiviral prophylaxis and one of oral versus intravenous pre-emptive treatment. Compared with placebo or standard care, pre-emptive treatment significantly reduced the risk of CMV disease (six trials, 288 patients: RR 0.29, 95% CI 0.11 to 0.80) but not acute rejection (three trials, 185 patient: RR 1.06, 95% CI 0.64 to 1.76) or all-cause mortality (two trials, 176 patients: RR 1.23, 95% CI 0.35 to 4.30). Comparative trials of pre-emptive therapy versus prophylaxis showed no significant difference in the risks of CMV disease, acute rejection or all-cause mortality.. Few RCTs have evaluated the effects of pre-emptive therapy to prevent CMV disease. Pre-emptive therapy is effective compared with placebo or standard care, but additional head-to-head trials are required to determine the relative benefits and harms of pre-emptive therapy and prophylaxis to prevent CMV disease in solid organ transplant recipients.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Humans; Immunocompromised Host; Opportunistic Infections; Organ Transplantation; Randomized Controlled Trials as Topic; Viremia

Topics: Acyclovir; Antiviral Agents; Graft Rejection; Herpesvirus 6, Human; Herpesvirus 7, Human; Humans; Immunocompromised Host; Lung Diseases, Interstitial; Opportunistic Infections; Roseolovirus Infections; Transplantation

Recent guidelines for the prevention of opportunistic infections have addressed a variety of issues germane to recipients of hematopoietic stem cell transplant. However, there are several issues regarding postexposure prophylaxis against varicella-zoster virus that remain unresolved. We address these questions and offer several consensus recommendations.

Topics: Acyclovir; Antiviral Agents; Disease Transmission, Infectious; Hematopoietic Stem Cell Transplantation; Herpesviridae Infections; Herpesvirus 3, Human; Humans; Immune Sera; Immunization, Passive; Immunocompromised Host; Neoplasms; Opportunistic Infections; Practice Guidelines as Topic; Secondary Prevention

Cytomegalovirus (CMV) infection and disease, with its extensive direct and indirect consequences, adds considerably to the cost of patient management in both solid organ and bone marrow transplantation. Antiviral prophylaxis for CMV infection can offer cost advantages over preemptive therapy and "wait-and-treat" approaches. Valacyclovir has demonstrated efficacy for CMV prophylaxis in renal, heart, and bone marrow transplantation and is cost-effective when compared with placebo in renal transplant recipients at high risk of CMV infection. In reducing CMV infection and disease, valacyclovir prophylaxis appears to be associated with reductions in indirect effects of CMV (acute graft rejection, other opportunistic infections) and, if these effects are considered, the potential exists for even greater savings to be made with valacyclovir therapy. Benefits of valacyclovir in transplantation extend beyond CMV to other herpesviruses and may be increased in some clinical situations by prolonging prophylaxis beyond 3 months.

Topics: Acyclovir; Administration, Oral; Antiviral Agents; Bone Marrow Transplantation; Cost-Benefit Analysis; Cytomegalovirus Infections; Graft Rejection; Health Care Costs; Heart Transplantation; Humans; Kidney Transplantation; Opportunistic Infections; Postoperative Complications; Prodrugs; Time Factors; Valacyclovir; Valine

A meta-analysis of 12 randomized trials (1574 patients) examined herpesvirus and related outcomes following organ transplantation over a range of acyclovir exposures (including valacyclovir). Overall, cytomegalovirus (CMV) infection (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.34-0.57; P<.001), CMV disease (OR, 0.41; 95% CI, 0.31-0.54; P<.001), death (OR, 0.60; 95% CI, 0.40-0.90; P=.01), opportunistic infection (OR, 0.70; 95% CI, 0.53-0.91; P=.009), acute graft rejection (OR, 0.67; 95% CI, 0.52-0.86; P<.001), herpes simplex virus disease (OR, 0.17; 95% CI, 0.12-0.24; P<.001), and varicella-zoster virus disease (OR, 0.06; 95% CI, 0.01-0.25; P<.001) were significantly reduced. Increased acyclovir exposure influenced more end points: Maximum efficacy resulted from valacyclovir (8 g/day). Increasing acyclovir exposure to that achieved with valacyclovir extends benefits of prophylaxis to include impact on graft rejection and opportunistic infections.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Graft Rejection; Herpes Simplex; Humans; Odds Ratio; Opportunistic Infections; Organ Transplantation; Postoperative Complications; Prodrugs; Randomized Controlled Trials as Topic; Treatment Outcome; Valacyclovir; Valine

Despite advances in prophylaxis and treatment, cytomegalovirus (CMV) infection remains a significant problem in the solid-organ transplant recipient. In addition to the clinical manifestations of CMV infection, there is also the immunosuppressive effect of CMV, which confers increased risk for fungal and other opportunistic infections. In reference to heart transplant recipients, the possible connection between CMV infection and rejection or CMV infection and allograft vasculopathy are areas of active research. Recent diagnostic advances, such as the CMV antigenemia assay and CMV-DNA detection by polymerase chain reaction or direct hybrid capture, have enabled early detection and monitoring of CMV infection and have raised the question of the implications of asymptomatic viremia. A wide variety of prophylactic strategies have been evaluated in heart and other solid-organ transplant recipients, including antiviral agents, globulin preparations, combinations of these therapies, and pre-emptive treatment strategies based on early detection or identification of a high-risk subset of patients. Many of these regimens have demonstrated efficacy in certain groups of patients, but a consensus has yet to emerge in terms of a single preferable strategy. Future advances on the horizon include the development of newer antiviral agents and a vaccine.

Topics: Acyclovir; Antiviral Agents; Cytomegalovirus Infections; Ganciclovir; Graft Rejection; Heart Transplantation; Humans; Immunization, Passive; Immunoglobulins; Immunoglobulins, Intravenous; Opportunistic Infections; Postoperative Complications

Topics: Acyclovir; Combined Modality Therapy; Cytomegalovirus Infections; Foscarnet; Ganciclovir; Humans; Immunization, Passive; Liver Transplantation; Opportunistic Infections; Pentamidine; Pneumonia, Pneumocystis; Pneumonia, Viral; Trimethoprim, Sulfamethoxazole Drug Combination

Chickenpox is the result of primary infection with the varicella zoster virus (VZV), which--like other herpes-viruses--has the ability to remain latent within the nervous system; reactivation then sometimes causes shingles many decades later. While chickenpox is benign in normal children, infection in the immunocompromised patient is characterized by a period of prolonged viral replication, delayed healing and a high frequency of extracutaneous manifestations, such as pneumonitis and involvement of the nervous system. Therefore, current therapeutic research efforts have focused on both the prevention of VZV infections through the development of a live, attenuated vaccine and improved therapeutic modalities. The existing antiviral drug acyclovir has been shown to be effective in reducing severe complications in risk groups. It has been generally accepted that the varicella vaccine is useful in immunocompromised children with acute leukaemia or solid malignant tumours. Healthy seronegative siblings will also benefit from the varicella vaccine. In addition, zoster hyperimmunoglobulin has also been shown to provide protection against primary VCV infection in the incubation period. Preventive and therapeutic efforts should mean that varicella will soon no larger be a medical problem even for immunocompromised patients.

Topics: Acyclovir; Chickenpox; Herpesvirus 3, Human; Humans; Opportunistic Infections; Risk Factors

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

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

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

Regarding the treatment of herpes zoster, aciclovir (ACV) is as the most effective and safe drug available. ACV reduces the viral shedding time and promotes the cutaneous healing and pain resolution. Oral ACV in high doses (5 x 800 mg daily), as well, has proved effective in the treatment of acute herpes zoster. If there is no convincing effect on the pain, additional application of corticoids in high doses may be of benefit.

Topics: Acyclovir; Antiviral Agents; Herpes Zoster; Humans; Opportunistic Infections

A 41 year old female developed reactive haemophagocytic histiocytosis secondary to herpes simplex infection, during remission induction for acute lymphoblastic leukaemia. She recovered fully with acyclovir and supportive treatment. Previous publications on the association between acute lymphoblastic leukaemia and haemophagocytic syndrome are reviewed, and the nature of the haemophagocytic disorder is discussed.

Topics: Acyclovir; Adult; Female; Herpes Simplex; Histiocytic Sarcoma; Humans; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction

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

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

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

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

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

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

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

Latent cytomegalovirus (CMV) infection is present in more than half the adult population, and a viral reactivation (ie, when the virus becomes measurable in body fluids such as blood) can occur in up to one-third of these individuals during episodes of critical illness.. To determine whether antiviral therapy is safe and effective for preventing CMV reactivation in a general population of critically ill patients.. A single-center, open-label, randomized, controlled clinical trial recruited 124 CMV-seropositive patients undergoing mechanical ventilation for at least 24 hours in the intensive care unit between January 1, 2012, and January 31, 2014. The mean baseline Acute Physiology and Chronic Health Evaluation II score of all patients was 17.6.. Patients were randomized to receive anti-CMV prophylaxis with valacyclovir hydrochloride (n = 34) or low-dose valganciclovir hydrochloride (n = 46) for up to 28 days to suppress viral reactivation, or to a control group with no intervention (n = 44).. Time to first CMV reactivation in blood within the 28-day follow-up period following initiation of the study drug.. Among the 124 patients in the study (46 women and 78 men; mean [SD] age, 56.9 [16.9] years), viral reactivation in the blood occurred in 12 patients in the control group, compared with 1 patient in the valganciclovir group and 2 patients in the valacyclovir group (combined treatment groups vs control: hazard ratio, 0.14; 95% CI 0.04-0.50). Although this trial was not powered to assess clinical end points, the valacyclovir arm was halted prematurely because of higher mortality; 14 of 34 patients (41.2%) had died by 28 days, compared with 5 of 37 (13.5%) patients in the control arm at the point of the decision to halt this arm. Other safety end points showed similar outcomes between groups.. Antiviral prophylaxis with valacyclovir or low-dose valganciclovir suppresses CMV reactivation in patients with critical illness. However, given the higher mortality, a large-scale trial would be needed to determine the clinical efficacy and safety of CMV suppression.. clinicaltrials.gov Identifier: NCT01503918.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Critical Illness; Cytomegalovirus; Cytomegalovirus Infections; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Opportunistic Infections; Respiration, Artificial; Valacyclovir; Valine; Virus Activation; Virus Inactivation

The objective of this study was to evaluate the comparability of systemic aciclovir exposure at steady state in immunocompromised patients following oral valaciclovir 1000 mg tds and intravenous (iv) aciclovir 5 mg/kg tds. A two-centre, randomized, open label, two-way crossover study was undertaken. Patients aged 18-65 years who had undergone high-dose chemotherapy for cancer and were neutropenic (neutrophil count <0.5 x 109/mL) with normal renal function were recruited. The pharmacokinetic parameters of aciclovir after oral valaciclovir 1000 mg or iv aciclovir 5 mg/kg given as 1 h infusion, each administered every 8 h for seven doses, were compared. Fifteen patients were enrolled and 13 completed both treatments. The mean (s.d.) values for aciclovir after oral valaciclovir and iv aciclovir were: AUC0-8 76.3 (29.7) and 64.2 (20.0) microM x h; peak plasma concentration (Cmax) 26.6 (10.5) and 34.0 (11.9) microM; time to maximal plasma concentration (tmax) 2.01 (0.65) and 0.95 (0.19); and plasma elimination half-life (t1/2) 2.83 (0.91) and 2.44 (0.62) h, respectively. The mean absolute bioavailability of aciclovir from oral valaciclovir was 60 +/- 21%. Equivalent systemic exposure to aciclovir after oral valaciclovir 1000 mg and iv aciclovir 5 mg/kg was observed with AUC0-8 (oral/iv ratio = 1.16; 90% CI 0.98-1.39), whilst significantly reduced peak aciclovir concentrations were obtained with oral valaciclovir (ratio = 0.75; 90% CI 0.60-0.94). Oral valaciclovir offers a convenient, and possibly safer, alternative to iv aciclovir, delivering comparable systemic exposures with reduced peak levels. This may contribute to shorter hospitalization, reduced costs for healthcare providers and improved quality of life for patients.

Topics: Acyclovir; Administration, Oral; Adolescent; Adult; Aged; Antiviral Agents; Female; Herpes Simplex; Humans; Immunocompromised Host; Infusions, Intravenous; Male; Middle Aged; Neoplasms; Opportunistic Infections; Valacyclovir; Valine

The optimal prophylactic regimen to prevent cytomegalovirus (CMV) infection and disease in orthotopic liver-transplant patients remains to be established. We tested whether a combination of intravenous ganciclovir (GCV) followed by high dosages of oral acyclovir (ACV) for 4 months provided a higher degree of protection from CMV than oral ACV alone.. One hundred sixty-seven liver-transplant recipients were randomized to receive 120 days of antiviral treatment starting at the time of transplantation consisting of either ACV 800 mg orally four times daily (n=84) or 14 days of GCV 5 mg/kg intravenously every 12 hr followed by oral ACV 800 mg four times daily (n=83). Prospective laboratory and clinical surveillance was performed to determine primary endpoints (onset of CMV infection and CMV disease) and secondary endpoints (rates of fungal and bacterial infection, allograft rejection, and survival after transplantation). One-year event rates are presented as cumulative percentages.. During the first year after transplantation, CMV infection developed in 57% of patients treated with ACV and in 37% of patients treated with GCV + ACV (P=0.001). CMV disease developed in 23% of patients treated with ACV and in 11% of patients treated with GCV + ACV (P=0.03). In seronegative recipients of allografts from CMV-seropositive donors (D+/R-), CMV disease developed in 58% of patients treated with ACV and in 25% of patients treated with GCV + ACV (P=0.04). In the D+/R- group, 54% of patients treated with ACV and 17% of patients treated with GCV + ACV developed infection with Candida albicans (P=0.05).. Prophylaxis of CMV infection in liver-transplant patients with 14 days of intravenous GCV followed by high-dosage oral ACV is more effective than high-dosage oral ACV alone at reducing CMV infection and disease, even for patients in the D+/R- CMV serological group.

Topics: Acyclovir; Adult; Antiviral Agents; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Ganciclovir; Graft Rejection; Humans; Incidence; Liver Transplantation; Male; Middle Aged; Opportunistic Infections; Survival Rate

A randomized trial was performed to compare the sequential use of 2 weeks of intravenous ganciclovir (10 mg/[kg.d]) followed by 50 weeks of high-dose oral acyclovir (800 mg/m2 four times daily) with 2 weeks of intravenous ganciclovir alone as prophylaxis for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) disease after pediatric liver transplantation. CMV disease was diagnosed for seven of 24 patients treated with ganciclovir followed by high-dose oral acyclovir compared with two of 24 children treated with ganciclovir alone (P = .048). Similarly, the rate of CMV disease among high-risk patients (CMV-positive donor/CMV-negative recipient) treated with the combination regimen was higher than that among high-risk patients treated with ganciclovir alone (four [57%] of seven vs. zero of five, respectively; vs P < .05). The rate of EBV disease among patients treated with the combination regimen (eight [33%] of 24) was similar to that among patients treated with ganciclovir alone (five [21%] of 24; P = not significant). We conclude that sequential prophylaxis with 2 weeks of intravenous ganciclovir followed by 50 weeks of high-dose oral acyclovir did not decrease the frequency of CMV or EBV disease after pediatric liver transplantation when compared with 2 weeks of intravenous ganciclovir alone.

Topics: Acyclovir; Administration, Oral; Adolescent; Antiviral Agents; Child; Child, Preschool; Cytomegalovirus; Cytomegalovirus Infections; Double-Blind Method; Ganciclovir; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Injections, Intravenous; Liver Transplantation; Opportunistic Infections; Postoperative Complications; Tumor Virus Infections

Oropharyngeal shedding of herpes viruses (herpes simplex, cytomegalovirus) was assessed in patients on standard acyclovir prophylaxis during bone marrow transplantation (BMT) to determine the frequency of viral shedding and to assess possible oropharyngeal complications that may be associated with viral reactivation in these patients. We conducted a prospective assessment of 83 patients receiving BMT. Patients were evaluated weekly and oral surveillance cultures were completed. Shedding of herpes simplex virus (HSV) was detected in the oropharynx of 2.9% of seropositive patients on prophylactic acyclovir, and only one case of clinical oral herpetic infection was seen. Cytomegalovirus (CMV) was cultured from the oropharynx in 13.3% of CMV seropositive patients provided with prophylactic acyclovir, but no oropharyngeal lesions were attributed to CMV reactivation. No correlation was seen between HSV and CMV pretransplant serology and severity of oral mucositis and acute graft versus host disease. No effect on time to engraftment was detected. This study supports the continuing use of acyclovir prophylaxis in HSV seropositive patients receiving BMT. Acyclovir prophylaxis was effective in preventing viral shedding in all but 2.9% of patients, and only one case of clinical infection was diagnosed. The frequency of CMV shedding was approximately four times that of HSV; however, no oral lesions were attributed to CMV.

Topics: Acyclovir; Adolescent; Adult; Antibiotic Prophylaxis; Antiviral Agents; Bone Marrow Transplantation; Cytomegalovirus Infections; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Opportunistic Infections; Prospective Studies; Stomatitis, Herpetic

Clinical course of herpes zoster was assessed in 119 immuno-competent and in 28 immuno-compromised hosts. Complications of herpes zoster were observed in one third cases. However, the frequency of post-herpetic neuralgia was lower than that seen by other authors. Despite severe underlying diseases in compromised hosts, good outcome of herpes zoster was obtained. It may be related to the use of aciclovir in all these cases. Early and rational treatment with aciclovir is important for decreasing of the frequency of severe complications of herpes zoster.

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Antiviral Agents; Bacterial Infections; Female; Herpes Zoster; Humans; Immune Tolerance; Male; Middle Aged; Neuralgia; Opportunistic Infections; Polyradiculoneuropathy; Treatment Outcome

To evaluate (a) the prophylactic effect of the antiherpetic drug acyclovir on oral ulcers in patients with acute myeloid leukaemia receiving remission induction chemotherapy and thus (b), indirectly, the role of herpes simplex virus in the aetiology of these ulcers.. Randomised, double blind, placebo controlled trial.. 74 herpes simplex virus seropositive patients aged 18-84. Thirty seven patients received acyclovir (800 mg by mouth daily) and 37 placebo. The patients were examined daily for 28 days.. Occurrence of herpes labialis, intraoral ulcers, and acute necrotising ulcerative gingivitis.. The two populations were comparable in age, sex, type of antineoplastic treatment, and history of herpes labialis. Acute oral infections occurred in 25 of the acyclovir treated patients and 36 of the placebo treated patients (relative risk 0.69 (95% confidence interval 0.55 to 0.87)). This difference was due to a reduction in the incidence of herpes labialis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)), intraoral ulcers excluding the soft palate (one case versus 13 cases; relative risk 0.08 (0.01 to 0.56)), and acute necrotising ulcerative gingivitis (one case versus eight cases; relative risk 0.13 (0.02 to 0.95)). However, ulcers on the soft palate were diagnosed with similar frequency in the two groups. Isolation of herpes simplex virus type 1 in saliva was reduced from 15 cases in the placebo group to one case in the acyclovir group (relative risk 0.07 (0.01 to 0.48)).. Intraoral ulcers excluding the soft palate are most often due to infection with herpes simplex virus, whereas ulcers on the soft palate have a non-herpetic aetiology. The findings suggest that acute necrotising ulcerative gingivitis may also be due to herpes simplex virus. Prophylaxis with acyclovir should be considered for patients with acute myeloid leukaemia during remission induction therapy.

Topics: Acute Disease; Acyclovir; Adolescent; Adult; Aged; Aged, 80 and over; Double-Blind Method; Female; Gingivitis, Necrotizing Ulcerative; Herpes Labialis; Herpes Simplex; Humans; Leukemia, Myeloid; Male; Middle Aged; Mouth Diseases; Opportunistic Infections; Stomatitis, Herpetic; Ulcer

Topics: Acyclovir; Adult; Boston; Candidiasis; Child; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Immunization, Passive; Immunoglobulins; Immunoglobulins, Intravenous; Immunosuppressive Agents; Liver Transplantation; Male; Muromonab-CD3; Opportunistic Infections; Placebos; Pneumonia, Viral; Risk Factors; Treatment Outcome

Topics: Acyclovir; Bacterial Infections; Cytomegalovirus; Cytomegalovirus Infections; Female; Follow-Up Studies; Graft Rejection; Humans; Immunization, Passive; Immunoglobulins; Immunoglobulins, Intravenous; Incidence; Kidney Transplantation; Male; Opportunistic Infections; Retrospective Studies; Virus Diseases

To study the effect of cytomegalovirus immune globulin (CMVIG) on prevention of cytomegalovirus (CMV) disease and its complications in patients receiving liver transplants.. Randomized, multicenter, placebo-controlled, double-blind trial.. Four university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation).. One hundred forty-one liver transplant recipients completed the study.. CMVIG or placebo (1% albumin) given in a dose of 150 mg/kg body weight within 72 hours of the transplant, then at weeks 2, 4, 6, and 8, and at 100 mg/kg at weeks 12 and 16.. Patients were observed for 1 year after transplantation for the development of CMV infection, disease, pneumonia, as well as for opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine, buffy coat, and throat wash for CMV for 2 months, then monthly, and at any clinical illness.. Using a Cox proportional hazards model, CMVIG was shown to reduce severe CMV-associated disease (multi-organ CMV disease, CMV pneumonia, or invasive fungal disease associated with CMV infection) from 26% to 12% (relative risk, 0.39; 95% CI, 0.17 to 0.89). When we controlled for the use of monoclonal antibodies to T cells (OKT3), CMVIG use was still protective (relative risk, 0.39; CI, 0.17 to 0.90). Rates of CMV disease were reduced from 31% to 19% (relative risk, 0.56; CI, 0.3 to 1.1) in CMVIG recipients although no effect on rates of CMV infection, graft survival, or patient survival at 1 year were shown. When we controlled for the urgency of transplantation and OKT3 use, a reduction in CMV disease (relative risk, 0.22; CI, 0.06 to 0.81) was shown for globulin recipients for all serologic groups except for the highest risk group (the CMV-seropositive donor, CMV-seronegative group).. CMVIG reduced the rate of severe CMV-associated disease in patients undergoing orthotopic liver transplantation. No effect of CMVIG on CMV donor-positive, recipient-negative liver transplant recipients was shown, suggesting a need for additional prophylactic strategies.

Topics: Acyclovir; Adult; Analysis of Variance; Cytomegalovirus Infections; Drug Therapy, Combination; Female; Humans; Immunoglobulins, Intravenous; Liver Transplantation; Male; Middle Aged; Multivariate Analysis; Opportunistic Infections; Postoperative Complications; Proportional Hazards Models; Risk Factors; Treatment Outcome

CMV infection is a major cause of morbidity and mortality following liver transplantation (LT). A prospective study of 218 LT recipients showed that 55% of patients developed CMV infection during the 1st year post-transplantation. Symptomatic CMV infection developed in 25% of all patients, being a major cause of death (21% of all deaths). Of 62 episodes of documented organ invasion, liver was the major site (38 episodes), followed by lung (20), gastrointestinal (4), and retina (4). The main patient group at risk (according to CMV serology of the recipient [(R)/donor(D)]) was the R-/D+: 77% of patients developed CMV infection, all of them with symptoms. The lowest group at risk was the R-/D-: 13% of patients developed CMV infection, half of whom developed symptoms. Time-dependent multivariate statistical analysis of risk factors indicated that the R-/D+ group was the main risk factor for CMV infection (P < .02) and symptomatic infection (P < .0001). To decrease the incidence and severity of CMV infection following LT, a randomized study is ongoing to evaluate the efficacy of ganciclovir (5 mg/kg/IV/q 12 hours for the first 14 days post-LT) followed by acyclovir (800 mg/po/qid for 14 weeks) GCV + ACV (group I), versus acyclovir (same dose for 16 weeks, starting immediately post-LT) ACV (group II). These treatment groups are compared to matched historical controls (C). Preliminary analysis of 83 LT recipients indicates that in group I the median date for the first evidence of CMV infection is delayed (82 days) as compared to group II and C (41 and 33 days, respectively) (P = .004).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acyclovir; Cytomegalovirus Infections; Ganciclovir; Humans; Incidence; Liver Transplantation; Multivariate Analysis; Opportunistic Infections; Prospective Studies; Risk Factors

The use of OKT3 therapy is a major risk factor for opportunistic infections in liver transplant recipients. In the last 2 years, we prospectively randomized 100 patients receiving OKT3 therapy into either a control group (n = 50) or a prophylaxis group (n = 50). Prophylaxis consisted of six doses of intravenous immune globulin over 4 weeks and oral acyclovir for 3 months after OKT3 therapy. The two groups were comparable with respect to demographic, immunologic, and clinical characteristics. The regimen of prophylaxis resulted in (1) a significant reduction in the incidence of herpetic and Epstein-Barr viral infections; (2) no change in the incidence of cytomegalovirus infections; (3) a significant decrease in the incidence of fungal infections; and (4) fewer deaths due to sepsis. The incidence of viral and fungal infections was higher after OKT3 induction than after rescue therapy. Our conclusion is that opportunistic infections are frequent after OKT3 therapy in hepatic allograft recipients. Treatment with intravenous immune globulin and oral acyclovir is safe and effective in preventing non-cytomegaloviral and fungal infections in this setting, thus conferring a survival advantage with fewer deaths due to sepsis.

Topics: Acyclovir; Adult; Antibodies, Viral; Antigens, Differentiation, T-Lymphocyte; CD3 Complex; Child; Child, Preschool; Cytomegalovirus; Drug Costs; Female; Humans; Immunoglobulins, Intravenous; Liver Transplantation; Male; Middle Aged; Muromonab-CD3; Opportunistic Infections; Prospective Studies; Receptors, Antigen, T-Cell; T-Lymphocyte Subsets

Our objective was to evaluate the efficacy and safety of zidovudine (250 mg every 6 h) alone or in combination with acyclovir (800 mg every 6 h) as treatment for AIDS-related complex (ARC). A double-blind, controlled clinical trial of 6 months therapy was conducted at teaching hospital ambulatory clinics in eight European countries and Australia; 199 patients were studied. Time to development of AIDS-defining opportunistic infections (OI) and AIDS-associated neoplasms, survival, performance status, body weight and CD4+ cell counts were measured. During the study six (9%) zidovudine recipients, five (7%) combination recipients and 12 (18%) placebo recipients developed AIDS-defining OI; the probability of developing an OI was 0.23, 0.09 and 0.08 for the placebo, zidovudine and combination recipients, respectively. Four patients in the placebo group, three in the zidovudine group and one in the combination group died during the study. Patients receiving zidovudine with or without acyclovir had moderate increases in CD4+ cell counts compared with placebo recipients and serum HIV p24 antigen level decreased significantly in all those receiving zidovudine. Fourteen (21%) patients in the zidovudine group and 16 (24%) in the combination group experienced bone-marrow suppression compared with three (5%) placebo recipients. Red-cell transfusions were administered to 6, 19 and 13% of placebo, zidovudine and combination recipients, respectively. These data confirm the efficacy of zidovudine therapy after 4 weeks' treatment in the reduction of development of OI in patients with ARC and support the use of a maintenance dose of 250 mg zidovudine 6-hourly. Given the increased development of OI in the treated groups compared with placebo during the first 4 weeks of therapy, we cannot exclude an initial adverse effect of zidovudine and recommend caution in the use of a loading dose of zidovudine. At 6 months there was no apparent difference in efficacy between the combination of zidovudine and acyclovir compared with zidovudine alone. Moreover, the addition of high-dose acyclovir resulted in a minimal increase in the risk of toxicity.

Topics: Acyclovir; Adult; AIDS-Related Complex; Double-Blind Method; Drug Therapy, Combination; Female; Herpes Simplex; Humans; Male; Neoplasms; Opportunistic Infections; Safety; Zidovudine

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

In 21 children with weakened immune response++ (18 patients after immunosuppression and/or after radiotherapy because of neoplastic disease, 1 patients with diagnosed hepatitis chronica persistens, 1 patient with streptococcal septicemia and one infant with protein deficiency and severe anemia) Zovirax was applied in treatment of Varicella virus infection. Clinical observation showed a positive effect of Zovirax in treatment of VZV infection which was manifested by a milder course of the infection and disappearance symptoms. Better effects were obtained when the treatment was started in the first 72 hours of infection.

Topics: Acyclovir; Adjuvants, Immunologic; Adolescent; Child; Child, Preschool; Clinical Trials as Topic; Female; Herpes Zoster; Humans; Immune Tolerance; Infant; Male; Opportunistic Infections

Topics: Acyclovir; Adolescent; Antiviral Agents; Chickenpox; Child; Child, Preschool; Clinical Trials as Topic; Herpes Zoster; Humans; Immune Tolerance; Infant; Neoplasms; Opportunistic Infections

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

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

Topics: Acyclovir; Aged; Antineoplastic Agents; Antiviral Agents; Bridged Bicyclo Compounds, Heterocyclic; Exanthema; Female; Hepatitis; Herpesvirus 3, Human; Humans; Immunocompromised Host; Leukemia, Lymphocytic, Chronic, B-Cell; Opportunistic Infections; Pancreatitis; Recurrence; Sulfonamides; Treatment Outcome; Varicella Zoster Virus Infection

Varicella-zoster virus (VZV) causes herpes zoster. Pneumocystis jirovecii (PJ) also causes pneumonia in immunocompromised hosts. Although both cause opportunistic infections, it is rare to have a co-infection in a non-human immunodeficiency virus carrier.. An 84-year-old woman with hemolytic anemia referred because of acute respiratory failure. She had received prednisolone without PJ pneumonia prevention. She developed dyspnea and desaturation while eating, and thus was treated based on a presumptive diagnosis of aspiration pneumonia. Physical examination revealed a vesicular rash on the left side of her neck suggesting herpes zoster infection. Polymerase chain reaction of her sputum for PJ and VZV was positive, which confirmed a diagnosis of pneumonia due to PJ and VZV co-infection. Despite acyclovir and sulfamethoxazole and trimethoprim administration, she died on hospital day 19.. Clinicians should suspect PJP when patients on systemic corticosteroids develop pneumonia and they have not received prophylactic treatment for PJP in non-HIV carriers. When such patients have a VZV rash, clinicians should aggressively seek signs of opportunistic infections. Our case hereby highlights the importance of recognizing the possibility of a VZV and PJ co-infection.

Topics: Acyclovir; Aged, 80 and over; Anti-Infective Agents, Urinary; Antiviral Agents; Coinfection; Fatal Outcome; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Opportunistic Infections; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Sputum; Sulfamethoxazole; Trimethoprim; Varicella Zoster Virus Infection

To describe a series of 5 patients with herpes simplex virus keratitis (HSK) and rheumatoid arthritis (RA) under immunosuppressive treatment.. Retrospective study. Detailed data were obtained regarding symptoms and signs at the initial evaluation, treatment, microbiological diagnostic tests, evolution, and outcomes.. Five patients with HSK and RA were identified. Bilateral involvement occurred in 2 patients (40%). Epithelial keratitis was diagnosed in 5 eyes. Three eyes showed severe melting with eye perforation. Gram-positive bacterial co-infections were common in the group with stromal keratitis. We did not find differences in the evolution of the disease based on anti-rheumatoid treatment.. The characteristics of HSK in patients with RA differed from HSK in immunocompetent patients. The stromal keratitis cases were very aggressive and difficult to manage, with perforation and gram-positive bacterial co-infection as frequently associated conditions. Prophylactic therapy at standard doses was unsuccessful to avoid recurrences.

Topics: Acyclovir; Aged; Antiviral Agents; Arthritis, Rheumatoid; Corneal Stroma; DNA, Viral; Female; Herpesvirus 1, Human; Humans; Immunosuppressive Agents; Keratitis, Herpetic; Male; Opportunistic Infections; Polymerase Chain Reaction; Retrospective Studies

Cytomegalovirus infection is a major cause of morbidity and mortality in solid-organ transplant. Low doses of valacyclovir have been administered as cytomegalovirus prophylaxis in our institution for years. To the best of our knowledge, there is no published study of a low-dose regimen for cytomegalovirus prophylaxis in heart transplant patients. Therefore, our aim was to determine the results of low doses of valacyclovir in heart transplant.. Between September 2006 and December 2014, sixty-eight patients underwent orthotopic heart transplants. All of the patients received triple immunosuppressive therapy after surgery. During the next 6 months, sulfamethoxazole/trimethoprim was administered for Pneumocystis jiroveci pneumonia, and toxoplasmosis. Additionally all patients received valacyclovir hydrochloride (1000 mg/d, oral) for cytomegalovirus prophylaxis and nystatin oral rinse for prophylaxis of fungal infections.. There was only 1 cytomegalovirus infection at follow-up. The patient had cytomegalovirus pneumonia at 17-month follow-up. In response to treatment with 1-week intravenous ganciclovir, the patient was discharged with a further 6-month oral valacyclovir therapy (1000 mg/d).. In this study, we hypothesized that daily use of low-dose valacyclovir (1000 mg/d) is not only sufficient for cytomegalovirus prophylaxis but also beneficial in terms of cost.

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Drug Administration Schedule; Drug Therapy, Combination; Female; Heart Transplantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Middle Aged; Opportunistic Infections; Pneumonia, Viral; Risk Factors; Time Factors; Treatment Outcome; Valacyclovir; Valine; Virus Activation; Young Adult

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome, usually presented with abnormal skin pigmentation, nail dystrophy, and oral leukoplakia. The main cause of mortality in DC is immunodeficiency and vital infection. DC involves multisystem, but retinal involvements are rare.Herein, we report an unusual case of pediatric DC suffering from frosted branch angiitis (FBA) after recovery of mycoplasma pneumonia. Cytomegalovirus infection and cytokine changes were found relevant to the onset of FBA. Despite corticosteroids, antiviral medication, and hematopoietic stem cell transplantation, the patient ended in poor vision with optic atrophy.This case implies that pediatricians should be aware of FBA as a rare retinal manifestation in children with DC and bone marrow failure. Cytomegalovirus may be one of the common causes and cytokines could be triggering factors.

Topics: Acyclovir; Anemia, Aplastic; Bone Marrow Diseases; Bone Marrow Failure Disorders; Child; Combined Modality Therapy; Cord Blood Stem Cell Transplantation; Dyskeratosis Congenita; Fluorescein Angiography; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Hemoglobinuria, Paroxysmal; Humans; Male; Methylprednisolone; Opportunistic Infections; Optic Atrophy; Pneumonia, Mycoplasma; Retinal Vasculitis; Retinal Vessels; Tomography, Optical Coherence

Over 26 years, we found 46 infectious episodes in 350 kidney transplant recipients. Fifteen were urinary tract infections, recurrent in 4 patients. There were 8 cytomegalovirus infections, three of them fatal when intravenous (IV) ganciclovir was not available. Seven patients had a reactivation of tuberculosis (TB) in the pleura, cervical spine, lumbar spine, knee, ankle, skin and peritoneum, respectively, and were all resolved satisfactorily with conventional anti-TB therapy. Three patients transplanted before routine prophylaxis with the use of acyclovir developed an extensive herpes zoster infection in the 1st 6 months after transplantation, which was resolved with the use of oral acyclovir, and 1 had a disseminated herpes simplex infection resolved with the use of IV acyclovir. Three patients transplanted before routine prophylaxis with trimethoprim sulfa developed Pneumocystis carinii pneumonia in the 1st 6 months after transplantation, which was fatal in one of them. In 2 patients, we found a Nocardia infection, confined to the lung, which was cured in one of the cases and systemic and fatal in the other. Two patients transplanted before routine prophylaxis with the use of nystatin developed esophageal candidiasis in the 1st 6 months after transplantation. One patient developed infective endocarditis in a stenotic bicuspid aortic valve and died 10 years later after another incident of infective endocarditis at the prosthetic aortic valve. Two patients developed an extensive condyloma at the penis, perianal region, and perineum owing to human papillomavirus, requiring extensive surgical resection and podophyllin applications. Another patient developed fatal post-transplantation lymphoproliferative disease due to Epstein-Barr virus infection 15 years after transplantation. One patient developed a severe and fatal mucocutaneous leishmaniasis with no response to conventional antimonial therapy. It is interesting to note that despite Chagas disease being endemic in Bolivia, we had no patients with reactivation or transmission through the graft even though many of the patients and donors were serologically positive for Chagas disease.

Topics: Acyclovir; Adolescent; Adult; Aged; Bolivia; Child; Cytomegalovirus Infections; Epstein-Barr Virus Infections; Female; Ganciclovir; Herpes Simplex; Herpes Zoster; Humans; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Pneumonia, Pneumocystis; Postoperative Complications; Retrospective Studies; Tuberculosis; Young Adult

Topics: Acyclovir; Aged; Facial Paralysis; Female; Follow-Up Studies; Herpes Labialis; Humans; Infusions, Intravenous; Opportunistic Infections

We report a challenging case of an atypical presentation of recrudescent herpes simplex virus infection in a patient with common variable immunodeficiency. Oral infections in immunosuppressed patients may present with unusual clinical features that can mimic non-infectious diseases. This report discusses the diagnostic steps necessary for definitive diagnosis and to guide appropriate and effective management.

Topics: Acyclovir; Antiviral Agents; Common Variable Immunodeficiency; Diagnosis, Differential; Female; Humans; Immunocompromised Host; Lichen Planus, Oral; Middle Aged; Opportunistic Infections; Stomatitis, Herpetic; Valacyclovir; Valine

Topics: Acyclovir; Aged, 80 and over; Antibodies, Monoclonal, Murine-Derived; Antiviral Agents; Blister; Hemorrhage; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunologic Factors; Male; Opportunistic Infections; Purpura, Thrombocytopenic, Idiopathic; Rituximab; Valacyclovir; Valine

A 24-year-old black female (HIV-positive) was referred to our clinic with a 4-week history of an ulcerative lesion of the right upper and lower eyelids. She was on treatment for pulmonary tuberculosis and had been admitted to a secondary level hospital. She had no other ocular symptoms or signs. A tissue biopsy of the lesion revealed multinucleate squamous cells with ground glass viral nuclear inclusion bodies, indicative of herpes simplex virus (HSV) infection. The ulcer healed with oral and topical acyclovir therapy, confirming a herpetic origin. There is only one other reported case of this type of ulcerative eyelid lesion caused by HSV; the patient in this case was also immunocompromised.

Topics: Acyclovir; Adult; Antiviral Agents; Eyelid Diseases; Female; Herpes Simplex; HIV Infections; Humans; Opportunistic Infections; Ulcer; Young Adult

To describe postexposure prophylaxis (PEP) against varicella zoster virus (VZV) in children being treated for malignancy in the UK and Ireland: the population at risk, frequency of exposure, clinical practice and attitudes among healthcare providers.. An observational study in three parts: (1) a retrospective survey of serostatus at diagnosis of malignancy, (2) collation of varicella zoster immune globulin (VZIG) dispensing data over a 3-year period and (3) an online survey of paediatric oncologists' clinical practice and beliefs in relation to VZV disease and its prevention.. UK and Ireland.. Children diagnosed with malignancy in 2009 (serostatus survey) or receiving VZIG between April 2006 and March 2009 (VZIG dispensing study). Paediatric oncologists and haematologists working in tertiary paediatric oncology centres and related shared care units in the UK and Ireland (physician survey).. Of 1500 children diagnosed with malignancy each year, at least 24% are VZV seronegative. Few centres make efforts to prevent household exposure by vaccinating VZV-susceptible family members. Exposures to VZV result in the administration of PEP to approximately 250 children with cancer annually: half receive an intramuscular injection of VZIG while the remainder receive a course of oral aciclovir. The choice of PEP is made by doctors. There is no consensus among paediatric oncologists as to which is the better option, reflecting the lack of a secure evidence base.. A randomised controlled trial to compare the effectiveness and acceptability of VZIG and aciclovir as PEP against varicella is both desirable and feasible.

Topics: Acyclovir; Antibodies, Viral; Antiviral Agents; Attitude of Health Personnel; Chickenpox; Child; Child, Preschool; Drug Utilization; Epidemiologic Methods; Herpesvirus 3, Human; Humans; Immune Sera; Neoplasms; Opportunistic Infections; Post-Exposure Prophylaxis; Professional Practice; Randomized Controlled Trials as Topic

Biological agents such as inhibitors of tumour necrosis factor alpha (TNF-alpha ) are associated with the development of opportunistic infections. Although there are no international recommendations for the management of opportunistic infections, their prevention is a key safety issue for patients with inflammatory bowel disease (IBD). We report that chemoprophylaxis with oral valaciclovir was effective in preventing Herpes simplex virus (HSV-1) reactivation in a girl treated with infliximab for Crohn's disease.

Topics: Acyclovir; Adult; Anti-Inflammatory Agents; Antibodies, Monoclonal; Crohn Disease; Female; Herpesvirus 1, Human; Humans; Infliximab; Opportunistic Infections; Secondary Prevention; Valacyclovir; Valine; Virus Activation

Reactivation of latent varicella zoster virus is one infectious complication associated with the extensive immunosuppression necessary for hematopoietic stem cell transplant. Most cases are limited to skin and mortality is low. Isolated visceral zoster is rare, presenting with ileus/abdominal pain, hepatitis, and/or hyponatremia. We present 2 cases of visceral varicella zoster virus in adolescents with chronic graft-versus-host disease after hematopoietic stem cell transplant. Both presented with elevated liver enzymes, severe abdominal pain, and hyponatremia but lacked cutaneous involvement. Both received high-dose acyclovir and showed improvement, but eventually expired from hepatic failure. The diagnosis of visceral zoster can be difficult especially without cutaneous manifestations. Vigilance is necessary in patients with chronic graft-versus-host disease, abdominal pain, and/or hepatitis and antiviral therapy should be initiated promptly.

Topics: Acyclovir; Antiviral Agents; Chronic Disease; Fatal Outcome; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Herpes Zoster; Herpesvirus 3, Human; Humans; Leukemia, Myeloid, Acute; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Transplantation, Homologous; Virus Activation; Viscera; Young Adult

Topics: Acyclovir; Adolescent; Antiviral Agents; Aspergillosis; Azathioprine; Brain; Chickenpox; Disseminated Intravascular Coagulation; Fatal Outcome; Female; Humans; Immunosuppressive Agents; Lung; Lupus Erythematosus, Systemic; Lymphohistiocytosis, Hemophagocytic; Meninges; Multiple Organ Failure; Myocardium; Opportunistic Infections; Prednisolone

The effect of preemptive therapy on indirect sequelae associated with cytomegalovirus (CMV) in liver-transplant recipients has not been clearly delineated.. Thirteen years of outcome with the use of preemptive therapy were assessed in a cohort of 216 consecutive liver-transplant recipients.. The incidence of major infections (31% vs. 44.3%), bacterial infections (31% vs. 39.2%), bacteremia (19% vs. 29.1%), or fungal infections (3.4% vs. 7.6%) did not differ significantly for patients with CMV infection who received preemptive therapy compared with those who never developed CMV infection and did not receive antiviral prophylaxis for CMV (P>0.20 for all variables). The rate of opportunistic infections also did not differ when patients were stratified by primary CMV infection, reactivation infection, or no CMV infection. Recurrent hepatitis C virus (HCV) hepatitis occurred in 55.6% of the patients with CMV treated with preemptive therapy and 49.8% of those without CMV infection (P>0.20). The probability of survival at 6 months, 12 months, 2 years, and 3 years was also comparable for the two groups.. Liver-transplant recipients with CMV infection, including high-risk R-/D+ patients, when followed using the preemptive therapy approach had no significant difference in meaningful outcomes such as opportunistic superinfections, HCV recurrence rates, rejection, and survival when compared with the patients in whom CMV infection never developed and who did not receive antiviral prophylaxis for CMV.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Cytomegalovirus Infections; Female; Ganciclovir; Hepatitis C; Humans; Incidence; Liver Transplantation; Longitudinal Studies; Male; Middle Aged; Opportunistic Infections; Recurrence; Survival Analysis; Viremia

Immunosuppressive agents (azathioprine, methotrexate) are increasingly being used in the treatment of inflammatory bowel disease. The use of immunosuppressive agents is associated with a greater risk of opportunistic infections, the most frequent of which are those caused by cytomegalovirus and varicella zoster virus. We present four cases of opportunistic infections due to Herpesviruses in patients undergoing immunosuppressive treatment with azathioprine for Crohn's disease. We also review the literature published on this topic. Two patients presented cutaneous varicella complicated by pneumonia and esophagitis respectively, one patient had cutaneous herpes zoster and the other had fatal pneumonia possibly caused by the Herpesvirus. In the first three the clinical course of the infection was favorable after withdrawing immunosuppressant treatment and initiating treatment with aziclovir. In patients Crohn's disease azathioprine treatment increases the risk of opportunistic infection by Herpesvirus. However, in the absence of other factors that increase immunosuppression, these infections usually have a benign course with specific antiviral therapy.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Azathioprine; Chickenpox; Crohn Disease; Disease Susceptibility; Esophageal Diseases; Fatal Outcome; Female; Ganciclovir; Hepatitis, Viral, Human; Herpes Zoster; Herpesviridae Infections; Humans; Immunosuppressive Agents; Leukopenia; Lymphopenia; Male; Opportunistic Infections; Pneumonia, Viral

Cytomegalovirus (CMV) is a major pathogen in renal transplant patients causing significant post-transplant morbidity and mortality. Prophylactic antiviral therapy, currently implemented in most kidney transplant centres, has significantly reduced the incidence of CMV infection after transplantation. Oral ganciclovir has been shown to be an effective prophylactic agent in preventing CMV disease and infection with a demonstrated superior efficacy over oral acyclovir. Valacyclovir, a prodrug of acyclovir with a higher level of bioavailability than acyclovir, has also been shown to be effective in preventing CMV disease when given as prophylactic treatment.. In a retrospective analysis of 150 renal transplant recipients in our centre, we compared the efficacy of oral ganciclovir with valacyclovir in preventing CMV infection. Seventy-seven consecutive renal transplant recipients prophylactically treated with oral ganciclovir for 12 weeks after transplant were compared with 73 consecutive recipients treated with oral valacylovir for an equal length of time.. No difference was noted in the incidence of CMV infection between the two treatment groups (5.1 vs 5.4%) after a 6 month follow-up. Likewise, the incidence of acute rejection was similar in both groups (11.6 vs 6.8%). All cases of CMV infection occurred in high-risk patients (donor positive/recipient negative).. The prophylactic use of oral valacylovir is as effective as oral ganciclovir in reducing CMV infection and disease after kidney transplantation.

Topics: Acyclovir; Administration, Oral; Adult; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Ganciclovir; Graft Rejection; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Opportunistic Infections; Preoperative Care; Probability; Retrospective Studies; Risk Assessment; Treatment Outcome; Valacyclovir; Valine

Topics: Acyclovir; Antiviral Agents; Chickenpox Vaccine; Hematopoietic Stem Cell Transplantation; Herpes Zoster; Humans; Opportunistic Infections; Research Design

Topics: Acyclovir; Adult; Antiviral Agents; Biopsy; Esophagitis; Esophagoscopy; Fever of Unknown Origin; Herpes Simplex; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Opportunistic Infections; Risk Factors

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Bone Marrow Transplantation; Child; Drug Resistance, Microbial; Female; Graft vs Host Disease; Herpes Simplex; Humans; Leukemia; Male; Mouth Diseases; Opportunistic Infections

A 26-year old man was admitted because of acute abdominal pain. He had received an allogeneic bone marrow transplant (BMT) for aplastic anemia 6 months before. All physical, laboratory, roentgenographic, and ultrasonographic studies were performed but nondiagnostic. On the fourth hospital day the patient developed visual disturbance and on the following day skin eruption appeared. Laboratory findings revealed severe liver dysfunction. We diagnosed this case as varicella-zoster virus (VZV) infection with visceral dissemination. Antiviral therapy with acyclovir was initiated and abdominal pain markedly reduced and visual acuity was recovered after 4 days. In case of VZV infection, acute abdominal pain prior to skin eruptions is rare. However in such cases the patients are highly fatal due to visceral dissemination. Antiviral therapy begun before visceral dissemination of VZV is highly effective in preventing serious disease, whereas it is less effective after dissemination. We consider that early diagnosis and treatment of VZV infection is necessary for BMT recipients who are undergoing immunosuppressive therapy.

Topics: Abdominal Pain; Acute Disease; Acyclovir; Adult; Anemia, Aplastic; Antiviral Agents; Bone Marrow Transplantation; Herpes Zoster; Humans; Immunocompromised Host; Male; Opportunistic Infections; Transplantation, Homologous

Topics: Acyclovir; Administration, Oral; Antifungal Agents; Antiviral Agents; Fluconazole; Ganciclovir; Humans; Injections, Intravenous; Kidney Transplantation; Opportunistic Infections; Pancreas Transplantation

Mucositis is a common complication following chemotherapy. Clinical findings similar to herpetic infection are observed in some patients. Acyclovir administered in addition to empirical, antibiotic treatment improves the course of mucositis, and can also bring down the temperature. The aim of our study was to define the etiological influence of herpetic infection on the course of febrile neutropenia in patients with mucositis. A total of 34 patients with febrile neutropenia were divided into 2 groups: 15 with typical herpetic eruption, and 19 with non-specific mucositis. Both groups received 5-10 mg/kg acyclovir every eight hours together with empiric antibiotic treatment. The effect of acyclovir was studied, and results compared in the two patient groups. Body temperatures decreased in both groups, clinical symptoms, however, disappeared more slowly in the group with non-specific mucositis. The beneficial effect of acyclovir treatment was particularly well expressed in seropositive patients. In this group of patients, herpetic infections may recur under further chemotherapy. Thus, it would be useful to administer acyclovir to them prophylactically during risk periods.

Topics: Acyclovir; Adult; Aged; Antiviral Agents; Diagnosis, Differential; Female; Fever of Unknown Origin; Hematologic Neoplasms; Herpes Simplex; Humans; Male; Middle Aged; Neutropenia; Opportunistic Infections; Retrospective Studies; Stomatitis; Virus Activation

A boy with Wiskott-Aldrich syndrome suffered from thymidine kinase (TK)-altered and aciclovir-resistant herpes simplex virus type 1 (HSV-1) skin infections. He presented with severe herpes simplex around the left eye in March 1993 at the age of 8 years. HSV-1 strain TAS was isolated and was shown to be susceptible to aciclovir (50% inhibitory concentration (IC50) 0.23 microg/mL). He was treated with intravenous (i.v.) high dose aciclovir, 2 mg/kg per h, which produced an improvement. About 1 year later (May 1994), a severe herpes simplex infection appeared on his face, arm, genitalia, back and foot. Treatment with i.v. aciclovir, 2 mg/kg per h, was initiated, but the skin lesions did not improve. HSV-1 strain TAR was isolated and was shown to be resistant to aciclovir (IC50 36 microg/mL). HSV-1 TAR and TAS were susceptible to vidarabine (IC50 4. 4 and 2.9 microg/mL, respectively). The skin lesions were treated with i.v. vidarabine, 15-20 mg/kg per day, and healed satisfactorily. However, in March 1995, the patient again experienced a severe herpes simplex infection around the left eye. HSV-1 strain R95 was isolated and was shown to be resistant to aciclovir (IC50 36 microg/mL). Diminished sensitivity of HSV-1 TAR and R95 to aciclovir was associated with reduced viral TK activity and loss of aciclovir phosphorylation activity.

Topics: Acyclovir; Antiviral Agents; Child; Drug Resistance, Microbial; Herpes Simplex; Humans; Male; Opportunistic Infections; Recurrence; Wiskott-Aldrich Syndrome

Since 1990, we have treated all kidney transplanted patients with cyclosporin (CsA)+ an initial 10 d antilymphocyte globulin (ALG) course, from September 1995 supplemented with mycophenolate mofetil (MMF). In 170 consecutive transplantations from June 1992 to the end of 1996, aciclovir 3200 mg/d (adjusted for kidney function and in children to age) was given prophylactically for 3 months post-transplantation (Tx), monitored with systematic and frequent tests for HSV and CMV. In case of CMV infection, we gave ganciclovir intravenously (oral ganciclovir from 1996) in doses according to kidney function for 3 months, followed by a further 3 months observation and monitoring period. In case of acute cellular rejection, ganciclovir was given during the 10-d OKT3 course and 1 week further. In case of delayed graft function combined with aciclovir side effects, ganciclovir was given until aciclovir could be reintroduced.. 39% were HSV seronegative at Tx. There were no seroconversions or reactivations within the observation period. No mucocutaneous HSV infections was observed. No resistant strains developed. 26% were both HSV and CMV negative at Tx. 52% were CMV negative at Tx. 30% experienced a CMV infection post-transplant. The patients were grouped according to CMV status in the donor (D) and recipient (R) before Tx. We found approximately the same number of patients in the 4 CMV groups D-/R-, D+/R-, D-/R+ and D+/R+. Most infections occurred in the D+/R- group compared to D-/R- (p = 0.009). A significant increase in the number of CMV infections occurred in this subgroup when we gave reduced doses in case of delayed graft function (p = 0.015), from 1994. We observed only 1 CMV disease (in 1992). Serological EBV testing were performed concomitantly. No correlation was seen between CMV and EBV infections. From September 1995 we have treated all transplanted patients (n = 40) with CsA/ALG/MMF. We found no significant increase in CMV infections in this group.. Prophylaxis with aciclovir (combined with ganciclovir during acute rejections and in case of delayed graft function with aciclovir side effects) gives a good protection against HSV and CMV infections and prevents CMV disease effectively. High-dose aciclovir post-transplantation (or shift to ganciclovir) seems to be important to obtain effective prophylaxis. Better immunosuppression with MMF does not result in more CMV infections.

Topics: Acyclovir; Antigens, Viral; Antiviral Agents; Cytomegalovirus Infections; Epstein-Barr Virus Infections; Ganciclovir; Herpesviridae Infections; Humans; Immunocompromised Host; Kidney Transplantation; Opportunistic Infections

Lower respiratory tract infection is a major cause of morbidity and death after lung transplantation. The incidence and significance of noncytomegalovirus viral respiratory tract infections has not been reported to date. We report our center's experience with these infections.

Topics: Acyclovir; Adolescent; Adult; Cytomegalovirus Infections; Female; Herpes Simplex; Humans; Immunosuppressive Agents; Lung Transplantation; Male; Middle Aged; Opportunistic Infections; Pneumonia, Bacterial; Pneumonia, Viral; Postoperative Complications; Premedication; Risk Factors

Posttransplantation lymphoproliferative disorders (PTLDs) represent an important complication of solid organ transplantation. The main causative factor of PTLDs seems to be the intensity and type of immunosuppressive therapy and the frequent occurrence of Epstein-Barr virus infection. PTLDs that are disseminated at diagnosis or present late after transplantation generally share an unfavorable prognosis and are unlikely to regress in response to reduction in immunosuppressive therapy. We describe a case of cutaneous B-cell lymphoma occurring 4 years after heart transplantation in which molecular analysis revealed a monoclonal pattern of Epstein-Barr virus infection and immunoglobulin gene rearrangement. In spite of its monoclonal nature and late occurrence, the lymphomatous lesions regressed completely after antiviral treatment and a reduction in immunosuppressive therapy.

Topics: Acyclovir; Antiviral Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Heart Transplantation; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Lymphoma, B-Cell; Male; Middle Aged; Opportunistic Infections; Postoperative Complications; Prognosis; Skin Neoplasms; Tumor Virus Infections

Large papillomatous lesions clinically resembling verrucous carcinoma may be caused by viruses other than human papillomavirus. We report a case of recurrent vegetations covering the entire vulva in a pregnant patient with common variable immunodeficiency. Herpes simplex virus was recovered from these lesions. The patient did not respond to intravenous acyclovir, but her lesions dramatically healed with two courses of intravenous foscarnet. Repeated biopsies may prove necessary in cases such as this to ensure proper diagnoses.

Topics: Acyclovir; Adult; Biopsy; Common Variable Immunodeficiency; Drug Resistance, Microbial; Female; Fetal Death; Foscarnet; Herpes Genitalis; Herpesvirus 2, Human; Humans; Infant, Newborn; Opportunistic Infections; Pregnancy; Pregnancy Complications, Infectious; Recurrence

We report a patient with acute myeloblastic leukaemia who presented with a pneumonia and herpes simplex viraemia associated with primary herpes simplex virus-1 infection. The importance of detecting and treating viral infections in haematology patients is discussed.

Topics: Acyclovir; Aged; Female; Herpes Simplex; Herpesvirus 1, Human; Humans; Leukemia, Myeloid, Acute; Opportunistic Infections; Pneumonia; Viremia

Topics: Acyclovir; Adult; Ganciclovir; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Kidney Transplantation; Lymphoproliferative Disorders; Male; Opportunistic Infections; Treatment Failure

A 30-year-female with chronic myelogenous leukemia received allogeneic bone marrow transplantation (BMT). On day 104, low-grade fever, cough, and general malaise developed, resulting in hospitalization 10 days later. Chest X ray revealed diffuse infitrates, suggesting cytomegalovirus interstitial pneumonia. Ganciclovir (DHPG) was given daily and all symptoms disappeared three days later. However, a very few vesicular lesions appeared on her trunk and her two children had chickenpox at that time. Chest CT was taken and disclosed diffuse nodular shadows. Clinical course and chest CT suggested varicella pneumonia. DHPG administration was stopped and acyclovir PO started to be given. She was discharged in excellent condition. In this report, we show a rare case of varicella pneumonia after allogeneic BMT and efficacy of DHPG for the treatment of varicella pneumonia.

Topics: Acyclovir; Adult; Antiviral Agents; Bone Marrow Transplantation; Chickenpox; Female; Ganciclovir; Humans; Immunocompromised Host; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Opportunistic Infections; Pneumonia, Viral; Tomography, X-Ray Computed; Transplantation, Homologous

Our data suggest that CMVIG in combination with ganciclovir effectively reduces the incidence, and delays the onset of CMV infections in seropositive lung transplant recipients. In addition, its use may be associated with less severe CMV infection and a lower incidence of bacterial or fungal opportunistic infection. Although the number of patients in the study is small, high-titer CMVIG may be more effective than standard titer immunoglobulin in the prevention of CMV disease in lung transplant recipients. Several questions remain in addition to these: What is the optimal dosage and duration of treatment with CMVIG for prophylaxis of CMV infection and disease in lung transplant recipients; Is this strategy cost-effective; Will it reduce the incidence of obliterative bronchiolitis following lung transplantation and enhance allograft survival? A prospective, random-assignment trial is warranted to answer these questions.

Topics: Acyclovir; Antibodies, Viral; Cytomegalovirus; Cytomegalovirus Infections; Ganciclovir; Humans; Immunization, Passive; Immunoglobulins; Immunoglobulins, Intravenous; Immunosuppressive Agents; Incidence; Lung Transplantation; Opportunistic Infections; Pneumonia, Viral; Survival Analysis; Viremia

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

We report a case of a 76-year-old patient who developed an atypical form of varicella zoster virus (VZV) reinfection. In addition to histological and serological confirmation of diagnosis, direct demonstration of VZV-DNA was possible by means of the nested polymerase chain reaction. Although VZV infection is usually diagnosed by clinical examination, the nested PCR is a sensitive and specific diagnostic procedure that can be useful especially in atypical cases.

Topics: Acyclovir; Aged; Azathioprine; Chickenpox; Cytopathogenic Effect, Viral; Female; Herpesvirus 3, Human; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Opportunistic Infections; Pemphigus; Polymerase Chain Reaction; Prednisone

Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients.. One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol.. Mean age was 33 (range, 19-59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent), Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas. Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months +/- 2.9 SEM (range, 1-94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures.. Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.

Topics: Acyclovir; Adult; Anus Diseases; Chlamydia; Combined Modality Therapy; Cytomegalovirus; HIV Seropositivity; Humans; Male; Middle Aged; Mycobacterium; Neisseria gonorrhoeae; Opportunistic Infections; Prospective Studies; Rectal Diseases; Risk-Taking; Simplexvirus; Treatment Outcome

Topics: Acyclovir; Adult; Chickenpox; Herpes Simplex; Herpes Zoster; Humans; Opportunistic Infections

Cytomegalovirus (CMV) is the most common opportunistic pathogen following renal transplantation and remains a major concern in transplantation centers owing to its high morbidity and impact on renal allografts. Pending more effective antiviral drugs, efforts have been directed toward prevention strategies. We conducted a retrospective analysis to evaluate the efficacy of various prophylactic options used at our institution during the period April 1986 to August 1990. All CMV-negative patients with CMV-negative kidneys (D-R-) received screened, CMV-negative blood products (n = 19). CMV-specific immunoglobulins (CMV Ig) were used in 6 patients at increased risk for primary CMV infection and acyclovir was administered to 21 patients at an initial intravenous dose of 5 mg/kg body weight; then oral doses of 800-3200 mg per day were given according to the patients' estimated creatinine clearance. Thirty-two patients did not receive any CMV prophylactic treatment and served as controls. CMV monitoring of the patients during the first 6 months after transplantation showed an overall infection and disease rate of 81% and 38.1%, respectively, in the acyclovir-treated group. Compared with controls, the incidences of infection and disease were higher in the acyclovir-treated patients, with a significant difference for CMV infection (P = 0.002, generalized Wilcoxon test). Only 1 of the 19 D-R- patients presented with CMV infection. CMV Ig-treated patients tended to have less severe disease without any apparent reduction in infection incidence. Given the high rate of infection in patients at risk, we infer that high-dose acyclovir does not prevent CMV infection in our setting of renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acyclovir; Adolescent; Adult; Cytomegalovirus; Cytomegalovirus Infections; Humans; Immunoglobulin G; Incidence; Kidney Transplantation; Middle Aged; Opportunistic Infections; Premedication; Retrospective Studies; Transplantation, Homologous; Treatment Failure; Viremia

Herpes simplex virus (HSV) infections causing severe disease are reported frequently in patients suffering from human immunodeficiency virus (HIV) infection. This disease pattern may also be seen in an immunocompromised disease state with other causes, however, as in the case presented in this paper. An 84-year-old woman had hepatic cirrhosis resulting from chronic hepatitis C virus infection. The woman developed ulcerative lesions in and around her mouth and in the genito-anal region, and these persisted for some months. Diagnosis of HSV infection was not obtained until after extensive laboratory investigations. Aciclovir infusion therapy started immediately afterwards led to dramatic improvement of the skin and mucous membrane changes. Complete clearing of lesions was not obtained, however, because the patient died as a result of the immunosuppression.

Topics: Acyclovir; Aged; Aged, 80 and over; Female; Fluorescent Antibody Technique; Hepatitis C; Herpes Genitalis; Herpes Simplex; Humans; Immune Tolerance; Inclusion Bodies, Viral; Liver Cirrhosis; Opportunistic Infections; Skin; Stomatitis, Herpetic

A 31-year-old woman with systemic lupus erythematosus (SLE) developed meningoencephalitis, followed by transverse myelitis. The clinical picture was otherwise not consistent with a lupus flare. Extensive diagnostic evaluation was unrevealing. Acute visual loss ensued, associated with an unusual pattern of retinitis. Endoretinal biopsy established the diagnosis of herpesvirus infection. Reinstitution of antiviral therapy, and optic nerve sheath decompression, led to resolution of neurologic deficits and partial return of vision. Our report is the first that describes a patient with SLE with herpes meningoencephalitis, transverse myelitis, and rapidly progressive outer retinal necrosis, diagnosed antemortem by endoretinal biopsy, and successfully treated with acyclovir and optic nerve fenestration.

Topics: Acyclovir; Adult; Biopsy; Central Nervous System Diseases; Combined Modality Therapy; Female; Herpesviridae Infections; Humans; Lupus Erythematosus, Systemic; Meningoencephalitis; Myelitis, Transverse; Opportunistic Infections; Retinitis

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

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

Topics: Acyclovir; Adult; Antiviral Agents; Drug Resistance, Microbial; Foscarnet; Herpes Simplex; HIV Infections; Humans; Male; Opportunistic Infections; Phosphonoacetic Acid; Skin Diseases

Topics: Acyclovir; Antilymphocyte Serum; Cause of Death; Clotrimazole; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Follow-Up Studies; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Function Tests; Kidney Transplantation; Muromonab-CD3; Opportunistic Infections; Pentamidine; Postoperative Complications; Survival Analysis; Survival Rate; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acyclovir; Adult; Combined Modality Therapy; Critical Care; Herpes Zoster; Humans; Immunocompromised Host; Lymphoma, Non-Hodgkin; Male; Opportunistic Infections

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

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

Herpes simplex encephalitis (HSE) carries a high mortality rate. Therefore, an early diagnosis and institution of acyclovir are essential. We report a case of biopsy-proven HSE with 2 negative cerebrospinal fluid (CSF) analyses and 2 normal CT scans. However, MRI together with EEG were abnormal early in the disease stressing their significant role in any suspected case of HSE. Although brain biopsy remains controversial, CSF herpes simplex antigen detection offers hope in providing an early or retrospective diagnosis while specific antiviral therapy with acyclovir is initiated. Overdependency on routine CSF analysis or head CT scan can result in unnecessary delays in diagnosis and treatment.

Topics: Acyclovir; Antibodies, Viral; Antigens, Viral; Biopsy; Brain; Electroencephalography; Encephalitis; Herpes Simplex; Humans; Magnetic Resonance Imaging; Middle Aged; Opportunistic Infections; Simplexvirus; Tomography, X-Ray Computed

Acute retinal necrosis (ARN) is increasingly being observed among patients with HIV infection. Varicella-zoster virus (VZV) and herpes simplex virus (HSV) are recognized as being the etiologic agents in this syndrome. Among the 538 patients with HIV infection (261 of these with AIDS), who were followed up in our department between 1985 and 1990, we diagnosed ARN in 4 cases. Three of these patients suffered from AIDS. Thus, ARN was the third-most-frequent form of retinitis in our patients with AIDS (prevalence 1.1%), following Cytomegalovirus (CMV) retinitis (17.2%) and toxoplasmosis-retinochorioiditis (2.7%). The course of ARN in patients with AIDS is demonstrated in four case reports. Special features of the retina are documented by photographs of the fundus. The authors suggest that patients with AIDS who experienced an episode of VZV- or HSV infection which necessitated high-dose systemic aciclovir therapy are at risk of developing ARN. We recommend that they be kept on virustatic maintenance therapy.

Topics: Acyclovir; Adult; Fluorescein Angiography; Follow-Up Studies; HIV Infections; Humans; Male; Opportunistic Infections; Retinal Necrosis Syndrome, Acute

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

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

Topics: Acyclovir; Adult; Cytomegalovirus Infections; Dose-Response Relationship, Drug; Female; Ganciclovir; Hepatitis, Viral, Human; Humans; Liver Transplantation; Male; Middle Aged; Opportunistic Infections; Retrospective Studies

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

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

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

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

Intravenous acyclovir and vidarabine were compared in the treatment of varicella-zoster virus (VZV) infection in 25 immunocompromised children--13 with acute lymphocytic leukemia, three with other types of cancer, two with immunodeficiency and in seven undergoing prednisolone treatment. Thirteen had varicella and 12 had herpes zoster. Acyclovir was given intravenously to five patients with varicella and to four with herpes zoster at a dose of 5-10 mg/kg every eight hours. Vidarabine was given intravenously to eight patients with varicella and to eight with herpes zoster at a dose of 10 mg/kg/day. In varicella, vidarabine significantly shortened the time from the start of treatment to cessation of new lesion formation compared with acyclovir. However, there was no significant difference in time to complete crusting between the two treatments. In herpes zoster, acyclovir significantly shortened the time from the onset of the skin lesions to complete crusting. A slight raise of GOT in two cases was reported. While acyclovir and vidarabine were equally effective for VZV infection, in herpes zoster acyclovir was more effective.

Topics: Acyclovir; Adolescent; Chickenpox; Child; Child, Preschool; Drug Administration Schedule; Female; Herpes Zoster; Humans; Male; Opportunistic Infections; Vidarabine

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

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

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

Topics: Acyclovir; Adult; Cytomegalovirus Infections; Ganciclovir; Heart Transplantation; Humans; Male; Myocarditis; Opportunistic Infections

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

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

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

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

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

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

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

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

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

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

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

The clinical and virologic efficacy of ganciclovir (9-[1,3-dihydroxy-2-propoxymethyl]guanine) in the treatment of severe CMV infections in solid organ transplant recipients was investigated. Twelve patients (9 liver and 3 kidney transplant recipients) with CMV retinitis, esophagitis, hepatitis, or pneumonia received ganciclovir at a dose of 0.75-7.5 mg/kg/day for 10-30 days (mean duration 17 days). Clinical stabilization or improvement occurred in 8 patients (67%). Serial liver biopsies in 6 liver allograft recipients with CMV hepatitis demonstrated substantial histologic improvement on treatment. Of 6 patients with CMV pneumonia, 4 (67%) recovered and survived. Cultures of blood and other sites became negative in 9 patients (75%). Three patients (25%) had recurrent viral shedding after treatment, but none of these relapsed with invasive infections. Mild neutropenia was the only side effect encountered but was frequent (67%). The overall survival rate was 50%. Ganciclovir is effective in reducing CMV shedding in solid organ transplant recipients and is well tolerated. Our experience suggests a clinical benefit as well in patients with severe, invasive CMV disease. Relapse, in contrast to patients with the acquired immunodeficiency syndrome, is infrequent.

Topics: Acyclovir; Biopsy, Needle; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Liver; Liver Transplantation; Opportunistic Infections

Twelve liver and 5 kidney transplant recipients with severe cytomegalovirus infection were treated with Ganciclovir (7.5 mg/kg/day, intravenously). Ten were evaluable (compatible clinical picture, organ involvement shown histopathologically or by culture, viremia, and absence of concomitant infection). All 17 patients were studied for adverse drug side effects. A total of 9 evaluable patients survived the infection; 1 died during treatment due to infection or drug toxicity. A death 19 days after completion of treatment was due to unrelated causes. Patients became afebrile after 2-9 days (mean, 5.3 days) of treatment. Liver function improved, pulmonary infiltrates cleared, and hypoxemia reversed during therapy. Viremia ceased during therapy in 9 patients; asymptomatic viruria persisted or recurred in 6 of 7 patients studied. No relapses occurred during follow-up (7-17 months; mean, 13 months). Transient neutropenia and thrombocytopenia occurred in 3 and 1 patients, respectively. Ganciclovir appears promising for treatment of severe CMV infection in patients with kidney or liver transplants.

Topics: Acyclovir; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Liver Transplantation; Opportunistic Infections; Pneumonia; Time Factors

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

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

Topics: Acyclovir; Blood Donors; Chickenpox; Cytomegalovirus Infections; Herpes Simplex; Herpesviridae Infections; Humans; Liver Transplantation; Opportunistic Infections; Time Factors; Tissue Donors

Topics: Acyclovir; Adolescent; Adult; Antiviral Agents; Child, Preschool; Cytomegalovirus Infections; Female; Ganciclovir; Heart Transplantation; Humans; Immunosuppression Therapy; Lung Transplantation; Male; Middle Aged; Opportunistic Infections; Ovarian Neoplasms; Pneumonia, Viral; Teratoma

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

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

Topics: Acyclovir; Aged; Encephalitis; Female; Herpes Zoster; Humans; Immune Tolerance; Male; Middle Aged; Opportunistic Infections

Immunocompromised patients are at high risk of developing herpes simplex virus infections caused by reactivation of the virus. Intravenous and oral formulations of acyclovir have been shown to prevent most of these infections during the major at-risk periods when given prophylactically. Immunocompetent patients may also experience reactivation of herpes simplex virus leading most often to recurrent genital or labial infections. For those patients who experience frequent attacks, oral acyclovir can prevent most recurrences and is well tolerated when given as continuous suppressive therapy.

Topics: Acyclovir; Administration, Oral; Herpes Simplex; Humans; Immune Tolerance; Injections, Intravenous; Opportunistic Infections; Recurrence

A simple plaque-reduction assay was used to determine the acyclovir sensitivity of herpes simplex virus isolates taken from patients enrolled int he acyclovir clinical trial programme. The resultant data revealed no reduction in acyclovir sensitivity in virus from those patients, with a normal immune status, receiving topical, oral or intravenous acyclovir for the treatment of acute disease episodes. In the treatment or prophylaxis of chronic herpes infections in immunocompromised patients reductions in sensitivity were observed but these were infrequent. Sensitive virus was later recovered from a small number of patients who had yielded resistant virus when they were followed through to the next recurrence.

Topics: Acyclovir; Administration, Oral; Administration, Topical; Animals; Drug Resistance, Microbial; Herpes Simplex; Humans; Injections, Intravenous; Microbial Sensitivity Tests; Opportunistic Infections; Recurrence; Simplexvirus; Thymidine Kinase; Vero Cells

Herpes simplex virus strains, isolated from three immunocompromised patients whose infections showed clinical resistance to acyclovir, were studied as treatment progressed. Virus isolated from two patients remained sensitive to acyclovir throughout. Isolates from the third patient, who had received a prolonged course of oral acyclovir, showed a sharp decrease in drug sensitivity which corresponded to loss of thymidine kinase activity. No changes in restriction endonuclease profiles were observed in isolates from the same patient as treatment with acyclovir progressed.

Topics: Acyclovir; Drug Resistance, Microbial; Herpes Simplex; Humans; Microbial Sensitivity Tests; Opportunistic Infections; Simplexvirus

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

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