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Sponsors and Collaborators: |
University of Washington Bill and Melinda Gates Foundation |
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Information provided by: | University of Washington |
ClinicalTrials.gov Identifier: | NCT00194519 |
The University of Washington has received funding to conduct a proof-of-concept trial to assess the impact of suppression of genital herpes on HIV infectiousness. This study (the Partners in Prevention Study) will enroll HIV discordant heterosexual couples in which the HIV-infected partner is co-infected with herpes simplex virus type 2 (HSV-2) to test the efficacy of twice daily (bid) acyclovir (400 mg) given to the HIV-infected partner to prevent transmission to his/her HIV negative partner(s). This randomized, double-blind, placebo-controlled proof-of-concept trial will provide evidence for the efficacy of HSV-2 suppression with daily acyclovir on HIV transmission among HIV-discordant couples among whom the HIV-positive partner is also HSV-2 seropositive with CD4 >250. The researchers hypothesis is that, by decreasing the frequency and amount of genital HIV shedding, standard doses of daily acyclovir 400 mg bid will reduce the rate of HIV transmission by 50% in HIV-discordant couples among whom the HIV-infected partner is HSV-2 positive.
Under the study protocol version 4.1.1, 3000 HIV-discordant heterosexual couples in which the HIV-positive partner is HSV-2 positive and has a CD4 count >250 will be recruited; participants will be followed for up to 2 years. A 4% per year HIV incidence in the placebo arm is assumed.
The first study site began enrolling participants on 17 November 2005. As of September 2006, 14 sites in Eastern and Southern Africa had participated in recruiting the 2300 HIV-discordant couples enrolled to date.
Condition | Intervention | Phase |
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HIV Infection Herpes Simplex, Genital Sexually Transmitted Diseases |
Drug: Generic acyclovir and matching placebo |
Phase III |
Study Type: | Interventional |
Study Design: | Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study |
Official Title: | Phase III Randomized Placebo-Controlled Trial of HSV-2 Suppression to Prevent HIV Transmission Among HIV-Discordant Couples |
Enrollment: | 3408 |
Study Start Date: | November 2004 |
Estimated Study Completion Date: | May 2009 |
Estimated Primary Completion Date: | November 2008 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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Acyclovir: Active Comparator |
Drug: Generic acyclovir and matching placebo
400 mg twice-daily oral
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Placebo: Placebo Comparator |
Drug: Generic acyclovir and matching placebo
400 mg twice-daily oral
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Herpes simplex virus type-2 (HSV-2) is the primary cause of genital ulcers and one of the most prevalent sexually transmitted diseases worldwide. Consistently, over 30 studies have found HSV-2 infection to be a risk factor for HIV acquisition with an overall relative risk of 2.1 in the studies that demonstrated HSV-2 preceded HIV infection. A recent study of HIV-discordant couples from Rakai, Uganda, has shown that at all levels of HIV viral load in the HIV-positive partner, HSV-2 infection in the susceptible partner increased the per-contact risk of acquisition of HIV five-fold, and GUD in the HIV-source partner increased the per-contact risk of HIV transmission five-fold. As strong as these epidemiological data are, an intervention trial is required to define the clinical and public health significance of these findings.
This trial will directly answer the extent to which HSV-2 infection increases infectiousness of HIV/HSV-2 co-infected persons and the relative reduction in HIV transmission among HSV-2 seropositive persons treated with daily suppressive antiviral therapy. Acyclovir has an acceptable safety profile for widespread STD treatment and is inexpensive, well-tolerated, and episodic and long-term suppressive therapy has not been associated with increased acyclovir resistance. Given high HSV-2 seroprevalence in HIV-infected persons (70-80%) and high HIV incidence in populations with high prevalence of HSV-2 infection worldwide, this approach could have great public health importance by providing a safe, acceptable, and cost-effective method to reduce HIV transmission among HIV-infected persons who are also HSV-2 seropositive.
Sites that have enrolled couples in this study include: Johannesburg (2 sites) and Cape Town, South Africa; Gaborone, Botswana; Kitwe/Ndola and Lusaka, Zambia; Nairobi, Kisumu, Eldoret and Thika, Kenya; Moshi, Tanzania; Kampala, Uganda; and Kigali, Rwanda.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Potential index (HIV-infected) participants must meet the following criteria (by self-report, unless otherwise indicated) in order to be eligible for inclusion in the study:
Potential partner (HIV-uninfected at enrollment) participants must meet the following criteria (by self-report, unless otherwise indicated) in order to be eligible for inclusion in the study:
Exclusion Criteria:
Potential index (HIV-infected) participants who meet any of the following criteria (by self-report, unless otherwise indicated) will be excluded from the study:
Potential partner participants who meet any of the following criteria (by self-report, unless otherwise indicated) will be excluded from the study:
Botswana | |
Botswana-Harvard Partnership | |
Gabarone, Botswana | |
Kenya | |
University of Nairobi | |
Nairobi, Kenya | |
Kemri - Ucsf | |
Kisumu, Kenya | |
Moi University - Indiana University | |
Eldoret, Kenya | |
Partners Study Thika Site | |
Thika, Kenya | |
Rwanda | |
Projet San Francisco-Emory University | |
Kigali, Rwanda | |
South Africa | |
Perinatal HIV Research Unit, University of Witswatersrand | |
Johannesburg, South Africa | |
Reproductive Health and HIV Research Unit | |
Johannesburg, South Africa | |
University of Cape Town | |
Cape Town, South Africa | |
Tanzania | |
Kilimanjaro Christian Medical College-Harvard University | |
Moshi, Tanzania | |
Uganda | |
Mulago Hospital - IDI | |
Kampala, Uganda | |
Zambia | |
Zambia-Emory HIV Research Project | |
Ndola/Kitwe, Zambia | |
Zambia-Emory HIV Research Project | |
Lusaka, Zambia |
Principal Investigator: | Connie Celum, MD, MPH | University of Washington |
Study Director: | Jairam Lingappa, MD, PhD, | University of Washington |
Study Chair: | Anna Wald, MD, MPH | University of Washington |
Responsible Party: | University of Washington ( Connie Celum MD MPH ) |
Study ID Numbers: | 04-1240-A-02, Gates Foundation Grant #26469 |
Study First Received: | September 13, 2005 |
Last Updated: | October 15, 2008 |
ClinicalTrials.gov Identifier: | NCT00194519 |
Health Authority: | United States: Institutional Review Board |
HIV infection HIV transmission genital herpes sexual intercourse sexual transmitted infection |
acyclovir HIV Seronegativity Treatment Naive HIV-discordant couples HIV serodiagnosis |
Herpes Simplex Sexually Transmitted Diseases, Viral Skin Diseases Herpes Genitalis Acquired Immunodeficiency Syndrome Genital Diseases, Male Immunologic Deficiency Syndromes Herpesviridae Infections |
Virus Diseases Genital Diseases, Female Skin Diseases, Infectious Acyclovir HIV Infections Sexually Transmitted Diseases DNA Virus Infections Retroviridae Infections |
Skin Diseases, Viral Anti-Infective Agents RNA Virus Infections Slow Virus Diseases Immune System Diseases |
Therapeutic Uses Lentivirus Infections Infection Antiviral Agents Pharmacologic Actions |