How do we prepare for the possible roll-out of a topical microbicide for the prevention of HIV infection in women? That was one of many key questions posed to Monday’s esteemed panelists at a meeting hosted by the U.S. Agency for International Development.
USAID called the meeting in response to the encouraging Center for the AIDS Program of Research in South Africa (CAPRISA) 004 trial results that came out in July at the International AIDS Conference in Vienna, which showed that coitally-dependent, 1 percent tenofovir vaginal gel was 39 percent effective in reducing the spread of HIV infection among South African women. Last week the results of a similar trial studying the effect of pre-exposure prophylaxis (PrEP), once-daily tenofovir pill among men who have sex with men were released, showing 44 percent effectiveness.
Participants included government officials, top researchers and representatives from nongovernmental organizations such as the Bill and Melinda Gates Foundation, a major funder of HIV prevention research.
The meeting focused on the need for confirmatory evidence, and an agreement on what that entails, to get these exciting new prevention tools into circulation. The FDA recently announced that a study currently underway, the Vaginal and Oral Interventions to Control the Epidemic (VOICE) Study, can be used as confirmatory evidence should the results support the CAPRISA findings. VOICE is evaluating the safety and effectiveness of both daily oral dosing and daily topical application of tenofovir gel to prevent sexual HIV transmission in women, and observing which method women are more likely to use regularly.
Future research goals include determining whether the tenofovir gel is safe and effective for pregnant women and how to integrate the gel into family planning services.
“The male circumcision experience offers a good example of how research findings can lead to development of policy, and a translation of that policy into regional guidelines and implementation,” said Dr. Kevin DeCock, Director of the Center for Global Health at the Centers for Disease Control and Prevention. “We need to agree on what kind of confirmatory evidence is required, how much, similarities and differences between oral and topical PrEP… we need to agree on all of that,” he said.
The ultimate goal, according to USAID Administrator Rajiv Shah; “Allowing for country-led, sustainable roll out of microbicides in a broad number of countries.” Shah said this will require earlier planning and a broad mobilization of partners, reaching women and understanding their thoughts about using these products, and performing product uptake analyses to understand the needs of those that the prevention products are trying to reach – in this case, women. “This marks our progress toward the empowerment of women,” Shah said.
Repeated several times was the urgent need to move ahead as quickly as possible with testing of the dapivirine-containing intravaginal ring. The ring delivers 25 mg of the antiretroviral over the course of 28 days, and is currently in Phase I/II safety and acceptability trials being conducted in Africa by the International Partnership for Microbicides (IPM). If successful, the ring will move on to Phase III trials to test HIV infection prevention effectiveness, scheduled to begin in Africa in 2011 with results due in 2015.
“One thing mentioned at the meeting was the need in this time of constrained resources for definition of the highest priority activities for funding,” said Renee Ridzon, MD, senior program officer at the Gates Foundation and a member of the Center for Global Health Policy’s Scientific Advisory Committee. In particular, she said, was the need for a collaborative effort and funding on the very costly late-stage trials.
Panelists also discussed opportunities for cost-cutting in the provision of the gel to the community once approved. The overall affordability of the CAPRISA microbicide is largely dependent on the price of the applicator and the wrapper, which currently constitute about 80 percent of overall production cost. Development of reusable and/or less expensive cardboard applicators are currently being explored by South African manufacturers.
Panelists highlighted that the effectiveness of these prevention interventions has a high, positive correlation with treatment adherence. A non-blinded trial in which participants know that they are not taking a placebo but all are receiving the drug which has been proven to be effective – might encourage greater adherence to the treatment regimen, and in turn show greater efficacy at the community level.
U.S. Global AIDS Ambassador Eric Goosby made an appearance at the all-day meeting, and was asked how the President’s Emergency Plan for AIDS Relief (PEPFAR) program will play a role in microbicide roll out. “I think we will play a role,” Goosby said. “We have sites across all of these [high HIV prevalence] countries already.”
CAPRISA Director Dr. Salim Abdool Karim was quick to point out that prevention programs are targeting high-risk HIV negatives, and not HIV positives, which might not make dissemination through PEPFAR as simple a task.
Many of the panelists also attended an event at the South African Embassy Tuesday morning, entitled “Women and Microbicides: What Comes after the CAPRISA Trial?” The embassy’s panelists included key constituents needed to drive the PrEP agenda forward, including Dr. Karim; the President of Research at FHI Dr. Ward Cates; and the Executive Director of CONRAD, which provided supplies of the tenofovir gel for the CAPRISA trial, Dr. Henry L. Gabelnick.
“Optimally there will be no delay in regulatory approval, licensure, and provision of these products to the populations that need them,” said USAID Health Development Officer Dr. Judy Manning, who also participated in the panel. The FDA granted the tenofovir gel fast-track approval in mid-October, which will allow documentation for the gel’s efficacy to be submitted as they become available, rather than all at once.