Randomised Controlled Trial Assessing the Impact of Genital Herpes Suppressive Therapy on HIV Shedding

Sponsor

French National Agency for Research on AIDS and Viral Hepatitis (Other)

Overall Status

Completed

CT.gov ID

NCT00158509

Collaborator

(none)

215

Enrollment

Location

Duration (Months)

19.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Herpes Genitalis HIV Infection	Drug: Valacyclovir	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Prevention

Official Title:

Efficacy of an HSV2 Genital Herpes Suppressive Treatment on HIV and HSV2 Genital Shedding Among Co-Infected Patients Receiving or Not Antiretroviral Drugs

Study Start Date :

Aug 1, 2004

Study Completion Date :

Jul 1, 2005

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

To assess the impact of HSV-2 suppressive therapy on HSV-2 shedding among co-infected women taking HAART or not needing HAART []

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Service d'Hygiene du Centre Muraz	Bobo-Dioulasso		Burkina Faso

Sponsors and Collaborators

French National Agency for Research on AIDS and Viral Hepatitis

Investigators

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