Genital herpes is a long-life sexually transmitted diseases which infects a large proportion of women in Africa. Its clinical symptoms are painful sores on the genitals, which heals after a few days. HIV infection can worsen genital herpes. In turn, it is possible that genital herpes increases the quantity of HIV secreted at the genital level in women infected by the 2 viruses. This study is dedicated to verify this hypothesis.

Condition	Intervention	Phase
Herpes Genitalis HIV Infection	Drug: Valacyclovir	Phase II

Further Study Details: 

Primary Outcomes: To assess the impact of HSV-2 suppressive therapy on HIV shedding among co-infected women taking highly active antiretroviral therapy (HAART) or not needing HAART
Secondary Outcomes: To assess the impact of HSV-2 suppressive therapy on HSV-2 shedding among co-infected women taking HAART or not needing HAART
Expected Total Enrollment:  215

Infection with Herpes Virus Simplex type 2 (HSV-2) is likely to represent the main cofactor involved in HIV transmission, either through clinical episodes or asymptomatic genital shedding. However, the definite proof of this concept has never been made through randomised controlled trials. Furthermore, the natural history of HSV-2 infection is poorly documented in sub-Saharan Africa, as well as the efficacy of the antiviral drug on virus transmission. The latter can be measured by HSV-2 genital shedding as a proxy.

The objectives of this research programme are to assess the impact of a suppressive treatment for genital herpes on HIV genital shedding among co-infected patients receiving HAART or not needing antiretroviral (ARV) drugs.

In order to achieve these objectives, we propose to perform 2 randomised double blind controlled trials nested within the ongoing cohort of sex workers in Bobo-Dioulasso.

While the increase of HIV transmission by HSV-2 infection stands as our main working hypothesis among HIV positive persons, the specific rationale for individuals taking ARV is the following: Does the potential cofactor effect of genital herpes on HIV remain present when the immunity is built up by ARV? In other words, is HSV-2 infection a public health issue in this group of people. The role of ARV on HIV transmission will also be assessed.

These 2 trials will be performed using exactly the same methodology and the same study treatment. We will use a parallel design with a baseline phase to take into account the important inter-individual variability of genital shedding. Each participant will be its own control. The baseline phase and treatment phases will each consist of 6 visits performed at a 2 weeks interval. The participants will receive either placebo or Valacyclovir 1g/day during the treatment phase (3 months).

The outcomes will be measured using both a qualitative and a quantitative measure of HIV shedding. The analysis will be conducted using an "intention to treat" and a "per protocol" approach.

At the end of our project, the working hypothesis will be much documented in women taking ARV or not. Furthermore, our results will constitute a reference for an upcoming therapeutic vaccine trial.

This work results from the collaboration of the Centre Muraz, the UMR 36 "AIDS and associated diseases" (Montpellier) and the London School of Hygiene & Tropical Medicine.

Ages Eligible for Study:  16 Years and above,  Genders Eligible for Study:  Female

Criteria

Inclusion Criteria:

• Infection with HIV-1 and HSV-2
• If required to take antiretrovirals according to WHO recommendations, should be on HAART for at least 4 months
• Written informed consent

Exclusion Criteria:

• Pregnancy or willing to be pregnant during the next 6 months
• Breastfeeding
• Renal failure
• Expected non-compliance with follow-up or study treatment

Burkina Faso
      Service d''''Hygiene du Centre Muraz, Bobo-Dioulasso,  Burkina Faso

Study chairs or principal investigators

Nicolas Nagot,  Principal Investigator,  London School of Hygiene & Tropical Medicine   
Philippe Mayaud,  Study Chair,  London School of Hygiene & Tropical Medicine   
Philippe Van de Perre,  Study Chair,  Montpellier University, France   

Study ID Numbers:  ANRS 1285
Last Updated:  September 11, 2005
Record first received:  September 9, 2005
ClinicalTrials.gov Identifier:  NCT00158509
Health Authority: Burkina Faso: Ministry of Health
ClinicalTrials.gov processed this record on 2005-09-13