Evaluating Tenofovir Gel in South Africa

Community members play important role in trial.

Family Health Research: 2008, Vol. 2, Issue 2

The Centre for the AIDS Programme of Research in South Africa (CAPRISA) and its partners are testing the effectiveness of tenofovir gel — a promising antiretroviral-based microbicide — in two South African communities. The intense collaboration between CAPRISA and the community of Vulindlela demonstrates just how vital community involvement can be in the preparation and conduct of a microbicide trial.

"Vulindlela is one of many communities we have worked in," says Dr. Quarraisha Abdool Karim, CAPRISA's associate scientific director and one of the principal investigators of the tenofovir gel trial. "But our experience in Vulindlela has been unique."

A semi-rural district outside of Durban, Vulindlela is home to almost half a million people. For years, the residents of Vulindlela had experienced the effects of AIDS on their community, watching as family graveyards filled up at an astonishing pace. Finally, the traditional village chief, or Inkosi, was compelled to take an unusual step: He contacted a group of local scientists.

Photo Credit: CAPRISA

The semi-rural district of Vulindlela, shown here, is one of two communities participating in the trial.

Dr. Abdool Karim was one of the scientists who met with the traditional leaders of Vulindlela one Saturday morning in 2001. After welcoming the visitors, the Inkosi apologized that he could not spend the entire day with the group, as planned. "He had several funerals to attend," recalls Dr. Abdool Karim.

In response to the concerns of the traditional leaders, CAPRISA conducted extensive research on the nature of the HIV epidemic in the community. For two years, scientists hosted focus group discussions with local stakeholders, studied the HIV cases from local clinics, and conducted "verbal" autopsies to establish the main causes of death in the community. Armed with these data, they were able to secure funding to establish an AIDS treatment program. Today, the program cares for more than 5,000 patients, including 1,300 who are receiving antiretro­viral treatment. As part of a community fellowship program, CAPRISA also trained 32 community members as HIV/AIDS educators.

The Trial ... Phase IIb study evaluating the safety and effectiveness of tenofovir gel in preventing HIV infection Enrolling 980 sexually active, HIV-uninfected women, ages 18 to 40, who are at high risk of acquiring HIV Being conducted at clinical research sites in Vulindlela and Durban Study participants randomized to use either 1 percent tenofovir gel or a placebo gel Participants counseled to apply the gel via single-use, prefilled applicators before and after intercourse Participants given free condoms and counseled on reducing the risks of infection Participants and their partners provided with free screening and treatment for sexually transmitted infections Results expected in 2010 ... And Why it is Unique First effectiveness trial of an antiretroviral-based microbicide First microbicide trial that an institution in the developing world is leading First microbicide trial that a South African government agency is co-funding First time that South Africa has secured an up-front voluntary license to manufacture and distribute a microbicide if it is proven effective Photo Credit: Elizabeth T. Robinson/FHI A research facility in Durban, South Africa, tests blood samples.

Despite these accomplishments, the prevalence of HIV remained high in Vulindlela. At last measure, about 55 percent of women ages 20 to 24 were infected. This alarming statistic highlighted the importance of finding an effective HIV-prevention method that women could control. Ultimately, CAPRISA selected Vulindlela as one of the study sites for its tenofovir gel trial, which began in May 2007.

Together, the researchers and local traditional leaders established the Vulindlela Community Research Support Group to function as a liaison between the community, study participants, and research team. The group is a mixture of community leaders, representatives from religious and women's organizations, young people, government health care providers, and other stakeholders who review study materials and provide advice on recruitment and retention. They also function as a conduit through which community members can voice any concerns about the trial or other research that CAPRISA is conducting.

So far, more than 3,000 women in Vulindlela have received general information about the tenofovir gel trial. Among these women, 800 volunteers have been screened, and 454 have been enrolled in the study. As a testament to CAPRISA's dedication to building research capacity in the region, all of the study staff — including the recruitment teams, community educators, and project managers — are South African.

Adherence A participant's adherence to the study regimen is absolutely vital for valid results in a trial. Yet, unstable living conditions and other stressors someitmes make it difficult for women to follow the directions for using the study products. The CAPRISA team has implemented an innovative Adherence Support Program to help increase adherence rates. The program is based on the intention-motivation-behavioral skills model of HIV prevention, which reduces the risk of infection through behavioral change. Before enrolling in the trial, potential participants learn about using the gel applicators, possible side effects of the gel, the time required to participate in the trial, and the benefits and risks of participating. Once enrolled, each woman receives tailored counseling provided by a nurse using an approach called "motivational interviewing." Counselors use various teaching techniques to emphasize that the gel has to be inserted within 12 hours before sex and again up to 12 hours after sex, no matter how many times a woman has sex within that period. This core message is summarized as BAT-24: a dose Before sex, a dose After sex, and not more than Two applications within 24 hours. Photo Credit: Elizabeth T. Robinson/FHI Explicit instructions on using the gel applicators, combined with tailored counseling during the trial, help participants adhere to the study regimen. When a woman reports problems with adherence, the nurse helps her develop a plan to address them. The counselor also writes "adherence support prescriptions" that spell out practical, customized suggestions for each individual's situation. CAPRISA CAPRISA is a nonprofit organization dedicated to researching new ways to prevent and treat HIV and tuberculosis, and to building local research infrastructure and capacity. CAPRISA is collaborating with CONRAD, FHI, and the South African Ministry of Science and Technology (through LIFElab) on its effectiveness trial of tenofovir gel. More information about the trial is available here.