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

Objective: 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. Design: 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. Methods: 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. Results: The summary treatment effect estimate was -0.33 (95% confidence interval: -0.56, -0.10, 95% population effects interval: -0.74, 0.08) log10 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. Conclusion: Current evidence suggests a range of favorable effects of acyclovir on plasma HIV-1 viral load among persons coinfected with HSV-2.