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Meta-analysis of randomized trials on the association of prophylactic acyclovir and HIV-1 viral load in individuals coinfected with herpes simplex virus-2.

ABSTRACT: To summarize the randomized evidence regarding the association between acyclovir use and HIV-1 replication as measured by plasma HIV-1 RNA viral load among individuals coinfected with herpes simplex virus (HSV)-2.Meta-analysis of seven randomized trials conducted between 2000 and 2009. Inclusion criteria composed of acyclovir or valacyclovir use as prophylaxis among individuals coinfected with HIV-1 and HSV-2 who were ineligible for highly active antiretroviral therapy. HIV-1 viral load was the outcome.Random-effects summarization was used to combine treatment effect estimates. Stratified and meta-regression analyses were used to compare estimated treatment effects by characteristics of trials and participants.The summary treatment effect estimate was -0.33 (95% confidence interval: -0.56, -0.10, 95% population effects interval: -0.74, 0.08) log(10) copies, an approximate halving of plasma viral load. However, there was marked heterogeneity (P < 0.001). Older median age, valacyclovir, higher compliance, earlier publication, and shorter study length were associated with a larger decrease in viral load as compared with their counterparts.Current evidence suggests a range of favorable effects of acyclovir on plasma HIV-1 viral load among persons coinfected with HSV-2.

SUBMITTER: Ludema C

PROVIDER: S-EPMC4501265 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Meta-analysis of randomized trials on the association of prophylactic acyclovir and HIV-1 viral load in individuals coinfected with herpes simplex virus-2.

Ludema Christina C Cole Stephen R SR Poole Charles C Chu Haitao H Eron Joseph J JJ

AIDS (London, England) 20110601 10

<h4>Objective</h4>To summarize the randomized evidence regarding the association between acyclovir use and HIV-1 replication as measured by plasma HIV-1 RNA viral load among individuals coinfected with herpes simplex virus (HSV)-2.<h4>Design</h4>Meta-analysis of seven randomized trials conducted between 2000 and 2009. Inclusion criteria composed of acyclovir or valacyclovir use as prophylaxis among individuals coinfected with HIV-1 and HSV-2 who were ineligible for highly active antiretroviral t ...[more]

PMID: 21666542

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Project description:BackgroundHerpes simplex virus (HSV) replication can be detected in the respiratory secretions of a high proportion of ventilated intensive care unit (ICU) patients. However, the clinical significance remains poorly defined. We investigated whether patients with ventilator-associated pneumonia not responding to antibiotics and in whom high levels of HSV could be detected in respiratory secretions benefit from acyclovir treatment.MethodsRespiratory secretions (bronchoalveolar lavage fluid or tracheal aspirates) were tested for HSV replication by quantitative real-time PCR. ICU survival times, clinical parameters, and radiographic findings were retrospectively compared between untreated and acyclovir treated patients with high (> 105 HSV copies/mL) and low (103-105 HSV copies/mL) viral load.ResultsFifty-seven low and 69 high viral load patients were identified. Fewer patients with high viral load responded to antibiotic treatment (12% compared to 40% of low load patients, p = 0.001). Acyclovir improved median ICU survival (8 vs 22 days, p = 0.014) and was associated with a significantly reduced hazard ratio for ICU death (HR = 0.31, 95% CI 0.11-0.92, p = 0.035) in high load patients only. Moreover, circulatory and pulmonary oxygenation function of high load patients improved significantly over the course of acyclovir treatment: mean norepinephrine doses decreased from 0.05 to 0.02 μg/kg body weight/min between days 0 and 6 of treatment (p = 0.049), and median PaO2/FiO2 ratio increased from 187 to 241 between day 3 and day 7 of treatment (p = 0.02). Chest radiographic findings also improved significantly (p < 0.001).ConclusionsIn patients with ventilator-associated pneumonia, antibiotic treatment failure, and high levels of HSV replication, acyclovir treatment was associated with a significantly longer time to death in the ICU and improved circulatory and pulmonary function. This suggests a causative role for HSV in this highly selected group of patients.

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Meta-analysis of randomized trials on the association of prophylactic acyclovir and HIV-1 viral load in individuals coinfected with herpes simplex virus-2.

Publications

Meta-analysis of randomized trials on the association of prophylactic acyclovir and HIV-1 viral load in individuals coinfected with herpes simplex virus-2.

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