Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary infections with herpes simplex virus are usually localized, whereas those with varicella-zoster virus always disseminate. Both viruses persist within the host and may cause recurrent infections. Newborns and immunocompromised individuals have a risk for severe disease. Acyclovir is the drug of choice for complications or in immunodeficiency.
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PMID:[Clinical aspects and therapy of Herpes simplex and Varicella-Zoster virus infections in practice]. 794 Apr 10

Valaciclovir, the L-valyl ester of acyclovir, is rapidly and extensively converted in humans to acyclovir after oral administration by first-pass metabolism. A phase I study was conducted in two cohorts of volunteers with advanced human immunodeficiency virus (HIV) disease (absolute CD4 lymphocyte count of < 150 cells per microliters) who received oral valaciclovir at dosages of 1,000 or 2,000 mg four times daily for 30 days. All patients were clinically stable without any changes in underlying HIV-related medications for > or = 6 weeks prior to entry in study; these medications were continued throughout the study. Multiple-dose administration of valaciclovir showed a generally favorable safety profile. Nausea, vomiting, diarrhea, and abdominal pain each were reported in < or = 31% of the patients; of these symptoms, only one episode of diarrhea was considered causally related to valaciclovir exposure. Four patients developed neutropenia (two at each dose level) which was not clinically significant. There were no renal or neurologic adverse events. Valaciclovir was rapidly absorbed and converted to acyclovir, with plasma valaciclovir levels generally undetectable or levels of < or = 0.4 microgram/ml. After 3 h postdosing, valaciclovir was not detectable in plasma. Acyclovir was measurable in plasma as early as 15 min following valaciclovir dosing, and plasma concentrations of acyclovir greatly exceeded those of valaciclovir. The mean values for the maximum concentration of drug in plasma, time to maximum concentration of drug in plasma, area under the concentration-time curve from 0 h to infinity, and apparent half-life of acyclovir obtained after single- and multiple-dose valaciclovir administration in HIV-infected patients were similar to those reported in normal healthy volunteers. The time to maximum concentration in serum and half-life of acyclovir after valaciclovir administration were approximately 2 and 3 h, respectively, which were similar to those reported after oral administration of acyclovir itself. The mean trough and peak acyclovir concentrations and the daily area under the concentration-time curve acyclovir values at steady state were 2.5 and 8.4 micrograms/ml and 120 h micrograms/ml, respectively, after a dosage of 2,000 mg of valaciclovir four times daily. These values were approximately fivefold greater than those achieved with high dosages of oral acyclovir (800 mg, five times daily) and were not affected by continued use of medications necessary for management of advanced HIV disease. Thus, 2,000 mg of valaciclovir given orally four times daily should be evaluated for its potential efficacy in suppressing cytomegalovirus and other herpes group virus infections not optimally managed with current oral acyclovir therapy.
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PMID:Phase I trial of valaciclovir, the L-valyl ester of acyclovir, in patients with advanced human immunodeficiency virus disease. 797 85

On August 14, 1987, the Centers for Disease Control revised the surveillance case definition for the acquired immunodeficiency syndrome (AIDS) to include several indicator diseases. The addition of herpes simplex virus (HSV) infections to the definition reemphasized the increasing frequency of severe HSV infections in patients also infected with the human immunodeficiency virus (HIV). These infections in patients with AIDS are associated with considerable morbidity similar to reports of HSV in other immunocompromised populations. Their spectrum can include persistent or recurrent genital disease, severe visceral involvement, and disseminated infection. Patients with AIDS also are at increased risk of drug toxicities when receiving treatment for HSV infections in addition to antiretroviral therapy. Acyclovir, a selective and specific inhibitor of HSV replication, has been the mainstay of safe and effective treatment for HSV for more than a decade. However, reports of acyclovir-resistant strains of HSV in patients with AIDS have been steadily increasing since 1989. Although foscarnet has been successful in treating acyclovir-resistant strains, foscarnet-resistant strains have also been isolated. The search to find novel approaches for the treatment and suppression of HSV in patients with AIDS has become an added challenge in the management of this devastating disease.
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PMID:Genital herpes simplex infections in patients with the acquired immunodeficiency syndrome. 799 87

During the past 5 years, 99 patients with herpes zoster were hospitalized and followed. Age, sex, localization of rash, complications, duration of hospitalization and treatment were analyzed. Most patients were in their 6th and 7th decades. Cranial nerve involvement was frequent (35%). A generalized rash was more common in those with immunodeficiency. Acyclovir (Zovirax) inhibited to some extent the spreading of the rash and reduced the frequency of herpetic neuralgia. Our findings are in accord with those in the literature.
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PMID:[Herpes zoster treated with acyclovir]. 820 May 84

Valaciclovir (BW256U87) is an L-valyl ester of acyclovir, which is extensively and almost completely converted to acyclovir. In healthy human volunteers, single valaciclovir doses of 100-1000 mg resulted in dose-proportional increases in acyclovir area under the curve (AUC). The 1,000 mg dose produced an acyclovir peak plasma concentration (Cmax) of 5-6 micrograms/ml, AUC6 of 19 hr. micrograms/ml, time to maximum plasma concentration (Tmax) of 1-2 hr, and half-life (T1/2) of 2.8 hr. Plasma valaciclovir peak levels were < 0.3 micrograms/ml, and the prodrug was undetectable after 3 hr. Multiple valaciclovir doses of 250-2,000 mg given four times daily for 10 days resulted in dose-proportional increases in acyclovir Cmax. There were less than proportional increases in the AUCs. No serious or unexpected adverse events or laboratory abnormalities were reported. In volunteers with advanced human immunodeficiency virus (HIV) disease (absolute CD4 lymphocyte count < 150 cells/microliters), acyclovir and valaciclovir pharmacokinetic results were nearly identical to those in healthy volunteers. At the 2 g dose administered four times daily, steady-state acyclovir Cmax = 8.4 micrograms/ml, Tmax = 2.0 hr, AUC6 = 30.5 hr. micrograms/ml, and T1/2 = 3.3 hr. Nausea, vomiting, diarrhoea, and abdominal pain were commonly reported; however, only one adverse event (diarrhoea) was causally linked to valaciclovir exposure. There were no renal or neurologic adverse events. Valaciclovir is well absorbed and is rapidly converted to acyclovir, resulting in three- to fourfold higher acyclovir levels than can be achieved with oral acyclovir, even in patients with advanced HIV disease. The safety profile is generally favourable, with no evidence of nephrotoxicity or neurotoxicity.
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PMID:Valaciclovir (BW256U87): the L-valyl ester of acyclovir. 824 83

When platelet counts were compared in 1986 and 1992 in 117 anti-HIV antibody positive and negative hemophilia patients, a clear decrease was found in the positive group. In 1992 platelet counts < 150 x 10(9) were present in 23.5% of the positive group in contrast to 5.8% of the negative group. Comparing platelet counts with other clinical parameters, a positive correlation was found with cholinesterase and a negative correlation with IgG in both the positive and negative groups, while negative correlations with beta 2-microglobulin and platelet-associated IgG were found in only the positive group. These findings implicate the chronic liver dysfunction present in hemophilia patients, apart from HIV infection, in the decrease in platelet counts, with immunodeficiency playing an additional role in the positive group. In the treatment of a hemophilia B patient showing decreased platelet counts, these counts increased consistent with the administration of Acyclovir and Zidovudine. It was demonstrated that HSV-1 and HIV-1 antigen are present on the soluble platelets of this patient and are recognized by antibodies in the patient's serum.
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PMID:[Thrombocytopenia in HIV-1 seropositive hemophiliacs]. 831 32

Recent use of antiviral drugs and the increase in the number of viral infections in immunocompromised hosts have led to the development of viral resistance. In this paper, the author reviews the antiviral drugs on the market, the antiviral susceptibility tests and presents a review of the literature concerning infections with resistant viruses. Acyclovir-resistant herpes simplex and varicella-zoster virus, ganciclovir-resistant cytomegalovirus and zidovudine-resistant human immunodeficiency virus will be discussed.
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PMID:[The emergence of viruses resistant to antiviral agents: a new challenge]. 846 73

Penciclovir [9-(4-hydroxy-3-hydroxymethylbut-1-yI)guanine], an effective antiherpesvirus agent, was found to be a potent and selective antiviral agent against intracellular hepatitis B virus (HBV) replication (drug concentration at which a 10-fold decrease in HBV DNA from the average level in an untreated culture was observed [EC90], 1.6 microM) and extracellular virion release (EC90, 0.7 microM) by cultured human hepatoblastoma (2.2.15) cells. Acyclovir and three other related 9-alkoxypurines with activity against either herpesviruses or human immunodeficiency virus were uniformly inactive against HBV. The activity of penciclovir is discussed in relation to recent findings related to its mode of action against HBV.
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PMID:Penciclovir is a selective inhibitor of hepatitis B virus replication in cultured human hepatoblastoma cells. 872 85

Cytomegalovirus (CMV) disease is a common complication of advanced human immunodeficiency virus (HIV) infection. Administration of oral valaciclovir, a valine ester of acyclovir, achieves sufficient plasma acyclovir levels to inhibit many clinical isolates. Acyclovir has been associated with enhanced survival in AIDS but not with CMV disease prevention. CMV-seropositive patients (1227) with CD4 cell counts <100/mm3 were enrolled in a randomized, double-blind trial. Valaciclovir, 8 g/day, was compared with acyclovir, 3.2 or 0.8 g/day, for CMV prevention; all three arms were compared for survival. The confirmed CMV disease rate was 11.7% among valaciclovir recipients and 17.5% in the pooled acyclovir arms, a 33% reduction in risk. Time to confirmed CMV disease was significantly longer for the valaciclovir group (P = .03). A trend toward earlier mortality for valaciclovir recipients was seen (P = .06). Toxicity and earlier medication discontinuation were more common in this group. Valaciclovir significantly reduces the risk of CMV disease. Further exploration of a better-tolerated dose is warranted.
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PMID:A randomized, double-blind trial of valaciclovir prophylaxis for cytomegalovirus disease in patients with advanced human immunodeficiency virus infection. AIDS Clinical Trials Group Protocol 204/Glaxo Wellcome 123-014 International CMV Prophylaxis Study Group. 941 69

A meta-analysis of 8 randomized trials (1792 patients, 2947 patient-years of follow-up) showed that acyclovir (> or = 3200 mg/day) offered a significant survival benefit (P = .006 by log-rank test) in human immunodeficiency virus (HIV) infection. The treatment effect did not vary significantly in patient subgroups of different CD4 cell counts, hemoglobin levels, age, race, and sex, and with or without AIDS diagnosis. Acyclovir treatment (hazard ratio, 0.78; 95% confidence interval [CI], 0.65-0.93), higher CD4 cell count (P < .001), higher hemoglobin level (P < .001), and younger age (P < .001) reduced the hazard of mortality. Acyclovir decreased herpes simplex virus infections (odds ratio [OR], 0.28; 95% CI, 0.21-0.37) and varicella-zoster virus infections (OR, 0.29; 95% CI, 0.13-0.63) but not cytomegalovirus disease or mortality from lymphoma or Kaposi's sarcoma. A survival advantage was seen specifically in studies with high incidence of clinical herpesvirus infections (> or = 25% per year). Given the wide confidence intervals, the small effect in low-risk patients, and recent changes in HIV therapeutics, the results should be interpreted cautiously, but the meta-analysis supports the importance of pathogenetic interactions between herpesviruses and HIV.
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PMID:Clinical efficacy of high-dose acyclovir in patients with human immunodeficiency virus infection: a meta-analysis of randomized individual patient data. 969 14


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