A second clinical trial studying pre-exposure prophylaxis (PrEP) in women in Africa has found that the intervention was no more helpful than a placebo in preventing new HIV infections, but that once again this was highly likely due to the fact that very few women were using the products as directed. These results were reported at the 2013 Conference on Retroviruses and Opportunistic Infections (CROI) in Atlanta
As with the previous trial showing poor results, called FEM PrEP, the VOICE trial enrolled women of child-bearing age in several African countries. With VOICE, just over 5,000 women were enrolled in three African countries. The women, with an average age of 25 and with nearly 80 percent being unmarried, were randomized to one of the following arms:
• take tenofovir (TDF) + emtricitabine (FTC), in a pill called Truvada
• takeTDF alone
• take a placebo pill
• take a gel containing TDF
• take a placebo gel
The gel and tenofovir arms were stopped early for futility, meaning that the results were already so poor as to render efficacy unlikely, in 2011. The Truvada arms continued through the end of the study in August 2012.
In the final analysis, VOICE researchers found that there were 15% fewer infections in the TDF gel arm than the placebo arm. There were 4% more infections in the Truvada arm than the placebo arm and nearly 50% more infections in the TDF arm. None of these reached statistical significance, however.
Though 90 percent of the women in all of the arms claimed that they took their pills or used their gel, an analysis of blood and vaginal fluids revealed that less than 30 percent were using the drugs at any time point. What’s more, because the blood and vaginal results only meant that the pills or gels were used within the last several days there is no way to know whether those with adequate blood or vaginal fluid levels were using the products daily as directed.
In all, both poor adherence and infections were more likely in younger women and unmarried women.
Attention must now turn to both better technologies for PrEP, including long-acting formulations available by injection or in vaginal rings. These would be far less vulnerable to poor adherence. Research focus must also be directed at better understanding adherence challenges and technology preferences of women in Africa.
We should be cautious, however, about assuming that these results can be extrapolated to all women or to women in the United States. Both the PARTNERS PrEP and TDF2 studies found relatively high rates of adherence and efficacy in women in Africa.