Abstract

Objectives: To determine the effect of daily acyclovir on genital shedding of HIV-1 and HSV-2 in a randomised placebo controlled trial among rural Zimbabwean sex workers.

Methods: Two hundred and fourteen women were recruited and tested for HIV-1 and HSV-2 antibodies, HIV plasma viral load (PVL), CD4 lymphocyte count and genital swabs for qualitative detection of HIV-1 and HSV-2 genital shedding. Women were randomised to acyclovir 400mg twice daily for twelve weeks or matching placebo and were followed weekly to detect HIV-1 or HSV-2 genital shedding. Shedding analyses were only undertaken on 125 women co-infected with HSV-2 and HIV-1. Data were analysed using logistic regression, with random effects modelling used to account for repeated measurements on the same women.

Results: All women were randomised to acyclovir or placebo; 125 of whom were co-infected with HIV-1 and HSV-2. Sixty nine women were randomised to acyclovir and 56 to placebo. Although twice daily acyclovir reduced rates of HSV-2 genital shedding, (adjusted OR 0.24 (95% CI 0.12-0.48; p<0.0001)), it had no effect on the proportion of visits at which HIV-1 shedding was detected (adjusted OR 1.08 (95% CI 0.48-2.42; p=0.9)). Adherence varied between participants but even when adherence was high (as determined by pill count and extent of HSV-2 suppression) HIV-1 shedding was not reduced.

Conclusion: Among these HIV-1 and HSV-2 sero-positive women, suppressive acyclovir therapy had no effect on the rate of HIV genital shedding despite reduction in genital HSV-2. Treatment adherence and its measurement clearly affect interpretation of these results.