A randomised placebo-controlled trial to explore the effect of suppressive therapy with acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 among Zimbabwean sex workers
- F M Cowan1,
- S J Pascoe2,
- K L Barlow3,
- L F Langhaug2,
- S Jaffar2,
- J W Hargrove2,
- N J Robinson5,
- M T Bassett4,
- D Wilson4,
- D W G Brown3,
- R J Hayes2
- 1Royal Free and University College Medical School, London, UK
- 2London School of Hygiene and Tropical Medicine, London, UK
- 3Health Protection Agency (HPA), London, UK
- 4University of Zimbabwe, Harare, Zimbabwe
- 5GlaxoSmithKline Research and Development, Brentford, UK
- Dr F M Cowan, Centre for Sexual Health and HIV Research, Royal Free and University College Medical School, University College London, Mortimer Market Centre, off Capper Street, London WC1E 6AU, UK;
- Accepted 3 July 2008
- Published Online First 6 August 2008
Objectives: To determine the effect of daily acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 (HSV-2) in a randomised placebo-controlled trial among rural Zimbabwean sex workers.
Methods: 214 women were recruited and tested for HIV-1 and HSV-2 antibodies, HIV plasma viral load, CD4 lymphocyte count and genital swabs for qualitative detection of HIV-1 and HSV-2 genital shedding. Women were randomly assigned to acyclovir 400 mg twice a day for 12 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 randomly assigned to acyclovir or placebo; 125 of whom were co-infected with HIV-1 and HSV-2. 69 women were randomly assigned to acyclovir and 56 to placebo. Although twice daily acyclovir reduced rates of HSV-2 genital shedding, (adjusted odds ratio (AOR) 0.24; 95% CI 0.12 to 0.48; less than p<0.001), it had no effect on the proportion of visits at which HIV-1 shedding was detected (AOR 1.08; 95% CI 0.48 to 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-seropositive women, suppressive acyclovir therapy had no effect on the rate of HIV genital shedding despite a reduction in genital HSV-2. Treatment adherence and its measurement clearly affect the interpretation of these results.
Funding: This study was part of a larger study funded by a grant from the Wellcome Trust. The research for this substudy was funded by GlaxoSmithKline Research and Development.
Competing interests: None.
Ethics approval: The study was approved by the Medical Research Council of Zimbabwe and the Medicines Control Authority of Zimbabwe. In addition the study had approval from the ethics committees of University College London and London School of Hygiene and Tropical Medicine.
Patient consent: Obtained.
Contributors: FMC drafted the paper and all authors commented on the draft. FMC designed the study and oversaw all aspects of the project implementation and evaluation. SJP was responsible for the preliminary statistical analysis for the paper. KLB validated and then undertook all the HIV and HSV-2 PCR analyses on genital and plasma samples. LFL supervised the day to day running of the project. SJ assisted with the study design and undertook statistical analysis. JWH was responsible for the initial statistical analysis and data management. NJR assisted with study design and analysis. MTB was involved in study design and facilitated implementation. DW was involved in study design and facilitated implementation. DWGB was closely involved in study design and the design of laboratory analyses. RJH was involved in study design and oversaw the statistical analysis.