San Diego, CA — At a symposium entitled “Challenges and Opportunities in HIV Prevention today at ID Week, Jean Marrazzo offered a summation of the pre-exposure phophylaxis (PrEP) research findings and highlighted some of the nuances and unanswered questions about disparate study results.
She began by defining the now widely used term “biomedical prevention” as a biological intervention that modifies a person’s risk of acquiring a disease or condition in the future, but reminded her largely physician audience that the behavioral component of such an intervention may be critical. Can you acquire the drug or device and can and will you take it? She also noted that one’s perception of individual risk and appreciation of the effectiveness of the intervention seem to be pretty strongly linked to adherence.
She used the Fem-PrEP trial to illustrate this—a large oral PrEP trial with a very high risk group of young African women. The trial found no difference in risk of HIV acquisition between the control group and the group that was offered oral antiretrovirals, and was stopped early with a stunning HIV incidence rate of 5 percent. Seventy percent of the women in the trial perceived themselves to be at little or no risk for HIV infection at the trial’s inception, despite the fact that only half reported using condoms and 6 percent of the women presented with gonorrhea and 14 percent with chlamydia. And even though most of the women reported taking their pills, for the majority, no tenofovir could be found in their blood samples.
Results from the VOICE trial have also been discouraging to date, since two of the trial arms testing topical tenofovir and the one testing oral tenofovir have already been stopped because of failure to show effectiveness. Results from the daily oral Truvada arm of the study are expected out by late winter.
This leaves scientists and program implementers to sort out why the IPREX and Partners Prep trial results were so much better. Marazzo suggests that figuring all this out requires a sophisticated understanding of biology and behavior. She pointed to a recent analysis of the Partners PrEP results that suggests that adherence to PrEP in discordant couples may be reinforcing because PrEP resolves tension in a committed HIV discordant sexual relationship and provides an opportunity to strengthen the relationship.This interplay may have implications for how to frame PrEP for vulnerable at risk populations.
Teasing out the reasons why the CAPRISA study showed 39 percent effectiveness and the FEM-PrEP study and two arms of the VOICE trial none leaves Marazzo and other scientists thinking that it is not all about adherence. There were differences in patterns and rates of other sexually transmitted infections between the studies. Are there problematic interactions between tenofovir and hormones? Where do different levels of genital inflammation fit in? Women who seroconverted in the CAPRISA trial tended to have higher levels of inflammation than those that did not. Genital tract characteristics may affect individual susceptibility to HIV infection. What was the frequency of anal intercourse among the women in the VOICE study using vaginal tenofovir gel? Twenty percent of the trial participants reported having anal intercourse during the three months prior to enrollment in the study.
While scientists grapple with these questions, other trials are underway. The ASPIRE study will test a new antiretroviral for prevention—the long acting dapivirine—in a vaginal ring in a Phase III clinical trial that is already 75 percent enrolled. Rilpivirine will also be studied for its prevention potential as a long acting injectable.
In the meantime, questions remain especially about the use of antiretrovirals as prevention in resource limited settings. Who to prioritize? How best to deliver? Do those who would benefit the most want it?