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HSV-2 Suppression Reduces HIV and HSV Shedding

December 2005

In an important proof of concept study presented at the 12th Annual Retrovirus Conference, Nicolas Nagot and colleagues from London School of Hygiene and Tropical Medicine, investigated whether suppressive treatment for herpes simplex virus (HSV) associated with genital herpes could have an impact on HIV transmission.1

The study randomized 140 women who were coinfected with HIV and HSV and were not eligible for ARV treatment, to either 1 gram valacyclovir daily for three months or placebo. Patients were followed for three months prior to randomization and for the three months during the study. HIV RNA and HSV DNA shedding in genital fluids were measured from cervical swabbing every two weeks.

The mean CD4 count at baseline was 519 and 482 cells/mm3 in the valacyclovir and placebo groups respectively. Overall visit attendance was reported as 93% and treatment adherence as 97%.

The reduction in HIV-1 RNA genital shedding was significantly greater in the valacylovir group than in the placebo group. HIV-1 shedding was significantly less persistent in the treated group. HIV-1 plasma viral load was also reduced in the valacyclovir group, as was HSV DNA shedding. The proportion of women shedding HSV at least once was 18.6% in the valacyclovir arm and 54.3% in the placebo arm.



A recent analysis by Freeman of studies in this area concluded that a person with genital herpes has an approximately threefold greater risk of acquiring HIV infection after sexual exposure.2

Genital ulcers provide a reduced physical barrier to HIV and increase activation of local CD4 and dendritic cells, which are susceptible to HIV infection. If the source partner is coinfected with HIV and HSV they may also have higher HIV virus levels in genital fluids and therefore be more infectious.

Previous studies have highlighted the protective effect of valacyclovir treatment on the transmission of HSV to non-infected partners,3 and data in this study supporting reduced risk of HIV transmission is clearly important. A similar benefit may be likely using the less expensive off-patent acyclovir.

Study Parameters
 Treated GroupPlacebo GroupP-Value
HIV RNA shedding in genital fluids (log copies/mL)0.26+0.090.003
Persistence of HIV RNA shedding (% of women)   
     At every study visit14.3%27.1% 
     At over half of study visits32.9%14.3% 
     At less than half of study visits32.9%14.3% 
     Never shed25.7%14.3%0.007
HIV RNA in blood (log copies/mL)0.39+0.12
HSV DNA shedding in genital fluids (log copies/mL)0.22+0.18
Women who shed HSV at least once (%)18.6%54.3%


  1. Nagot N, Ouedraogo A, Mayaud P et al. Effect of HSV-2 suppressive therapy on HIV-1 genital shedding and plasma viral load: a proof of concept randomized double-blind placebo controlled trial (ANRS 1285 Trial). 13th CROI, Denver 2006. Abstract 33LB.

  2. Freeman EE, Weiss HA, Glynn JR et al. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS 2006;20:73-83.

  3. Corey L, Wald A, Patel R et al. Once-Daily Valacyclovir to Reduce the Risk of Transmission of Genital Herpes. NEJM Volume 350:11-20 January 1, 2004.

From HIV i-Base. More treatment information is available at

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This article was provided by Gay Men's Health Crisis. It is a part of the publication GMHC Treatment Issues. Visit GMHC's website to find out more about their activities, publications and services.