Today the Microbicide Trials Network (MTN) research team published the final VOICE trial results in the New England Journal of Medicine with findings that add urgency, and perhaps optimism, to the women’s HIV prevention field as it counts the days until the late-February release of data from the FACTS 001 trial of the 1% tenofovir microbicide gel. (There is also a journal commentary entitled Preventing HIV in Women — Still Trying to Find Their VOICE.)
How does a publication of a trial that reported its results two years ago (and ended gel randomization and placebo control three years ago) raise the stakes today? To answer that question, it helps to look back at VOICE’s design and findings to date.
The VOICE trial was a five arm study designed to evaluate daily oral PrEP using TDF/FTC or TDF and vaginal 1% tenofovir gel as HIV prevention tools for women. The randomized, placebo-controlled components of the trial have been done for some time, and the bottom line from the trial was that there was no evidence of efficacy for any of the three interventions tested. Subsequent analyses of samples from participants showed that, even though the majority of women reported high levels of product use, actual adherence was very low. In AVAC Report 2013, we delved in-depth into what this finding meant—and how lack of efficacy in the context of low adherence is a finding that may say as much or more about how women feel about research and health systems as they do about how they feel about the products themselves.
The trial also found that all of the products were well tolerated and safe (to the extent that they were used) and that young women below the age of 25—who were most likely to acquire HIV—were also most likely not to use the products as prescribed.
VOICE D, a protocol launched after the original trial ended, has gathered a wealth of information about motivations for trial participation, misunderstandings in translation and terminology, and other issues that underpinned these findings. AVAC summarized some of these data in our updates from the recent HIV R4P conference.
VOICE is, in many ways, the richest source of information about why women-controlled products weren’t used, and therefore didn’t work, that the field has ever had.
This new publication adds a wrinkle and a glimmer of hope to this version of the VOICE story. A small subset of women provided blood samples that were analyzed for presence of the active ingredients in the experimental arm. Within that subset, an even smaller number had detectable drug in their blood. Researchers compared risk of HIV acquisition between women assigned to the tenfovoir gel arm who had detectable drug at their first quarterly visit (at month three visit) with women assigned to the tenofovir gel arm who had no detectable drug at their first quarterly visit. They found that women who received the gel and used it—per the sample at the three month visit—were 66 percent less likely to acquire HIV than women who did not. This finding was statistically significant. There was no association in similar analyses of women assigned to either the oral TDF or oral TDF/FTC arms.
What does this all mean? Conclusions can’t be drawn from small numbers. But this hint of efficacy sets the stage for the highly-anticipated release of data from the FACTS 001 microbicide trial which tested tenofovir gel in South African women. FACTS 001 used a different dosing regimen than the one used in VOICE, which asked women to use the gel on a daily basis. FACTS 001 asked women to use the gel before and after sex but no more than twice in 24 hours, the same “BAT 24” regimen used in the CAPRISA 004 trial that reported results in 2010 of modest HIV risk reduction across the whole trial, but—like this new data from VOICE—higher effectiveness among those women who used the gel (as determined by presence of tenofovir in blood samples).
As we await these data, advocates can use this new information to help as they continue to think through and prepare messages for a range of scenarios—including the possibility that FACTS 001 might have a finding like VOICE, or that it might not.
Does this type of finding support further evaluations of the same product? Does it suggest moving forward with methods that are less user-dependent? Or does it warrant piloting of the gel as is, to understand whether adherence improves once women know that the product works? It certainly puts all prevention advocates on alert for the FACTS 001 results expected in a few weeks—and adds to the evidence that we will need to put together to map the way forward.
These are just some of the questions that AVAC has been working with partners in several African countries to articulate and prepare to answer in the coming weeks and months. We’ve developed a range of materials and resources to help think through and explain these issues—and look forward to sharing them, thinking aloud and then acting on the data in the coming weeks.
Whatever the outcome from FACTS 001, the VOICE trial—with its almost 6 percent HIV incidence rate—is a reminder of the bottom line for us all: women need prevention tools they can and will use, and the research to find these tools must continue.