PARTNERS IN PREVENTION (PIP) TRIAL KISUMU SITE

The PIP Kisumu site is located at the Lumumba Health Center within  Kisumu municipality.  This study is a collaboration between Center for Microbiology research - KEMRI and the University of California San Francisco. This clinical trial is funded by the Bill and Melinda Gates Foundation through the University of Washington who are in collaboration with University of California San Francisco.
This study is a proof-of-concept trial to assess the impact of suppression of genital herpes on HIV infectiousness. 
 

It seeks to test the efficacy of twice daily acyclovir (400 mg) among HIV discordant couples where the HIV-infected partner is co-infected with herpes simplex virus type 2 (HSV-2) to prevent transmission to their HIV negative partner.
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 (up to 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
Our hypothesis is that standard doses of daily acyclovir 400 mg bid will reduce the rate of HIV transmission by 50% in these HIV-discordant couples by decreasing HSV-2 reactivation, and concomitantly, the frequency and amount of genital HIV shedding.

Study Design

The design of the study is a Phase III, multi-site, randomized double-blind, placebo-controlled, trial in which participants undergo treatment and follow-up for 24 months.

Study population
The study targets heterosexual HIV-discordant couples in which the HIV-infected partner also is HSV-2 seropositive with a CD4+ cell count > 250 cells/mm3 at screening and   not on antiretrovirals.

Study Size
The overall PIP intends to enroll 3000 HIV discordant couples (1500 in each treatment arm) recruited at  the twelve African sites. Kisumu site has a target of 300 couples to be enrolled in a period of two years (April 2005 to April 2007). Approximately two hundred couples already enrolled as at April 2006.

Treatment Regimen

HIV-infected study participants will be assigned at random in a 1:1 ratio to either 400 mg acyclovir or matching placebo, taken orally twice daily.
 

Individual Benefits:       

Participants in this study will receive CD4 testing and routine medical care and counseling.  Persons becoming symptomatic for AIDS or with CD4 counts <250 will be eligible for local programs providing antiretroviral therapy.  Counseling of HIV-discordant couples will reduce the risk of transmission for individual couples.

Community Benefits:     

Given the low cost of acyclovir, a positive finding in reducing HIV transmission could be of global public health benefit.  However, an important goal of this study is to achieve the study objectives in a way that provides benefits to the community that endure beyond the proposed four year study lifetime regardless of the specific outcome of the study.  Some of these community benefits are listed below:

• Development of couples VCT (CVCT):  Infrastructure to effectively counsel and test couples for HIV will be needed for this study to effectively recruit discordant couples.   CVCT capacity developed at participating sites in collaboration with existing local VCT programs through training of local counselors will be a beneficial resource to the community well after the study is completed. Given recent data that ~70% of incident HIV cases are transmitted from regular partner, creating awareness, increasing demand and constructing facilities for couples VCT should reduce transmission of HIV among couples.  This will have consequent benefits to the family and community by maintaining one healthy partner.  
• Enhanced laboratory capacity:  The study will enhance local laboratory specimen and data management infrastructure through use of electronic databases and networks.  The study will also provide technical training to ensure sustainable proficiency testing and quality control for HIV, HSV-2 and CD4 testing.

• Sustainable infrastructure for future HIV prevention and treatment trials: A sustainable infrastructure allowing high quality behavioral and laboratory research with HIV-discordant couples is needed to study vaccines and other preventive and treatment strategies for HIV. This will be developed in communities participating in this trial making them attractive sites for future studies (e.g., microbicide and vaccine trials) with consequent direct and indirect individual and community benefits.
•  Knowledge of community-specific biological factors for HIV transmission: This study may identify specific biological and social risk factors for HIV transmission that are unique to specific ethnic groups.  Knowledge about specific genetic and immunologic factors may lead to therapies, vaccines or other preventive tools that may specifically benefit such groups in participating communities.

Pip Kisumu Clinic At Lumumba Health Center  

Discordant Couple Recruitment

PIP Kisumu has employed a multi faceted approach to mobilize couples to seek CHCT services. This is being done in Kisumu, Nyando and Vihiga districts in Western Kenya. The outreach wing charged with the responsibility of mobilizing couples from the targeted communities has five major wings as outlined below;

Accelerated Mobilization

Faith based organizations

Work Place

Influential network Agents (INAs)

Voluntary Counseling and Testing (VCT)

The Kisumu site runs two stand alone C-VCT sites at Ondiek and Tivoli Aids Resource Center. The VCT wing collaborates with other VCT sites; Kisumu-; Vihiga-.to refer HIV discordant couples identified at those sites. A token of 4 US$ equivalent is paid to VCT counselors as transport reimbursement for every discordant couple referred and received at PIP Kisumu clinic. Other strategies used at the VCT include, individual partner arousal (partners who test alone are encouraged to invite their partners for the same) and couple refers couple (couples who have tested encouraged to invite other couples known to them). The VCT wing also conducts a four-day VCT counselors training on CHCT. Monthly counselors meetings are also held basically to discuss barriers to referral and mapping out way forward.

Challenges to Recruitment

Discordance is a new phenomenon and the public is still struggling to understand how it occurs and why one would remain negative while the partner is positive.
Most men test by proxy with the assumption that their partners HIV  results is same as their own.
Mobilization is labour intensive and covers a lot of extensive field work this requires vehichles which have been inadequate.
A few loss to follow up because of fake locator information and some of the participants have unrealistic expectation of the projects.