The introduction of new antiretroviral-based HIV prevention methods into health systems: an update

RHM published a discussion paper by me on the subject of new antiretroviral-based HIV prevention methods in the November 2011 journal issue,¹ which was written in August 2011. Subsequently, there were two important changes in the protocol of an ongoing clinical trial (VOICE) testing the effectiveness of HIV prevention methods discussed in the article. This is an update on those changes.

The Vaginal and Oral Interventions to Control the Epidemic (VOICE) study had been evaluating antiretroviral-based oral and vaginal methods for preventing transmission of HIV infection in Malawi, South Africa, Uganda and Zimbabwe. The study had enrolled 5,029 sexually active, HIV-negative women to test the daily use of two different oral antiretrovirals as pre-exposure prophylaxis (PrEP): tenofovir and a combination tablet containing emtricitabine and tenofovir (known by the trademark Truvada), and a vaginal gel containing 1% tenofovir.

In September 2011 oral tenofovir was discontinued from the study after a routine review determined that it was no more effective than the placebo used within the trial study group. Then, in December 2011, the study discontinued the use of the tenofovir-based vaginal gel after a routine review of data concluded that it was not effective in preventing HIV in the women enrolled in the trial.²

These two findings confound results presented in the previous Discussion piece regarding the efficacy of oral tenofovir and 1% tenofovir gel in prior trials, which had demonstrated a preventative effect on HIV transmission among women involved in those studies. The VOICE study will continue to test the safety and effectiveness of the oral use of combination emtricitabine and tenofovir as compared with placebo, given its relevance for understanding the potential for this combination to prevent HIV in different groups of women.

Two previous studies showed that daily use of the combination was effective in both men and women but it was not certain how generalisable the data from those studies were to single women, women with multiple partners, or women who may not know whether their husband/partner has HIV.

The lack of efficacy of oral tenofovir and 1% tenofovir gel has several implications, particularly for antiretroviral-based vaginal microbicides. The results of the CAPRISA 004 study released in July 2010 were an important milestone in the search for an effective microbicide. Some stakeholders began to urge for immediate deployment of the gel for use by women in settings where HIV is endemic. It was also felt that regulatory bodies could consider positive results from VOICE as a possible confirmatory trial of CAPRISA 004.

Overall, however, it was not felt that the landmark CAPRISA trial had provided all of the answers needed to introduce use of 1% tenofovir gel as a new HIV prevention strategy. VOICE was considered a critical study for obtaining further understanding of use of the gel. Women enrolled in VOICE used a once-daily dosing of 1% tenofovir gel. This is a different dosing regimen to the CAPRISA 004 trial, in which women used the gel 12 hours before sex and 12 hours after sex and no more than twice a day.

While the VOICE findings confound earlier trial results, the commentary and queries in the previous Discussion piece remain relevant. The conversation regarding whether there will be sufficient motivation to complete ongoing research on vaginal microbicides, given the efficacy of oral pre-exposure prophylaxis (PrEP) methods, has become more dynamic. Further tests of 1% tenofovir gel are planned in subsequent CAPRISA studies looking at different delivery options within health services.

Given the urgent calls for the release of effective HIV prevention strategies, particularly women-initiated vaginal microbicides, this is a frustrating development. These findings should remind health policy-makers of the need for significant support with correct adherence once these methods are finally available for use in the communities they have been designed to benefit.