April 8, 2015
Cindra Feuer is an AVAC staff member.
The Partners’ Forum rectal microbicide breakout session could not have come at a more strategic time. By the latter part of this year, the first Phase II rectal microbicide gel study, MTN 017, will come to an end with results expected in early 2016. However, it doesn’t seem likely that this product—which is a reformulated, reduced-glycerin cousin of the 1% tenofovir vaginal gel evaluated in CAPRISA 004, VOICE and, most recently FACTS 001—will move into the Phase III efficacy trial that has been discussed as the next step after MTN 017.
There are many reasons why the Phase III may not happen. There has been anecdotal evidence from MTN-017 and community gel discussion that the gel is not really lube-like (the applicator used to apply the gel means that it ends up in a different part of the rectum than what is lubricated during anal sex). There has also been criticism of the pre-filled applicator (the same one used in the trials of vaginal gel), with some finding it uncomfortable and burdensome to carry around and use. MTN 017 was designed to gather this kind of feedback. These reports are part of what has caused the field to pause. The recent disappointment from the FACTS trial has added to this.
FACTS 001 found that, even though women used the gel about 50 percent of the time, this level of adherence wasn’t high enough to reduce risk of HIV. In the meantime, daily oral PrEP is available today for people at risk of HIV, including the same men and transwomen who might want a rectal microbicide; long-acting injectable ARVs for prevention and treatment are also on the horizon.
The breakout session on rectal microbicides at the AVAC Partners Forum deliberated on new directions, demands and next steps for the rectal microbicide field. Participants felt strongly that there was a need and desire for rectal microbicides even with the advent of oral PrEP. They declared strongly that research should continue.
The second key message took some serious consideration, weighing the urgency of the need and desire for a rectal microbicide against the realities of what is available today, and the promise of the longer-term pipeline. But in the end, the group decided that its recommendation was that anecdotal evidence from MTN 017 should be taken seriously and rectal tenofovir gel shouldn’t move into phase III because of lack of acceptability of the applicator and the fact that the gel does not function like a lubricant—meaning two products would still need to be used. The group heard a description of Microbicide Trials Network’s (MTN) proposed Phase II Adonis Study design comparing different strategies for delivering a rectal microbicide, looking beyond the current applicator.
The group also weighed in on longer-term efforts and agreed on the need to: Keep a robust pipeline moving through development, including dapivirine gel Phase I to start this year; douche microbicides; and preclinical compounds especially Griffithsin, a non-ARV microibicide.
And, of course, the group was all in favor of continuing rectal microbicide research in South Africa, one of the homes to MTN 017, the first rectal gel study on the continent.
There was recognition for a revived African advocates voice in support of these demands on the IRMA listserv, which is closely followed by a range of researchers and leaders in the field, including scientists at the MTN and NIH—as well as PrEP, vaccine and all-around prevention researcher Linda-Gail Bekker of the South African Desmond Tutu HIV Foundation who declared at the Forum, “If you aren’t following IRMA, you haven’t lived!”