"Question 1(c)"

When FDA's Antiviral Advisory Committee finally voted last night whether to recommend an HIV prevention indication for Truvada (see previous posts), it turned out that some of the suspense was unwarranted: for men who have sex with men and HIV negative people in serodiscordant relationships (i.e., their stable partner is HIV positive), the group voted 19-3 and 19-2, respectively, to recommend approval. 

The vote on "Question 1(c)," however (the panel voted on each proposed indication one at a time), was much closer.  The question was whether to recommend approval for indication in "Other individuals at risk for acquiring HIV through sexual activity."  As a committee member noted before the vote, this question was primarily about heterosexual women, many of whom face a high risk of HIV acquisition in the U.S. (not to mention globally), but in whom the clinical trials data have been less conclusive.  It has been widely noted that the FEM-PrEP trial, testing Truvada in heterosexual women, was stopped when an interim review showed that it would not demonstrate efficacy.  It has emerged subsequently, however, that adherence in FEM-PrEP was too low for the trial to have demonstrated an effect, regardless of the pill's actual efficacy.  Women have been included in other studies of oral tenofovir-based products (including Truvada), but neither of those studies was powered to draw conclusions by gender.  At the same time, it is biologically plausible that the products would not work in women, based on relatively low drug concentration in vaginal tissue associated with Truvada (compared to levels found effective in CAPRISA 004 from a topical tenofovir product, or compared to levels found in rectal tissue in men).  Thus, the shortage of efficacy data in women was a curveball for the panel, deciding how broadly to approve the indication for Truvada.

The committee voted 12-8 to approve the wider indication.  This close vote signals that the most interesting question, in advance of the FDA's anticipated June 15 decision on labeling, may be the "1(c)" population.  FDA appears likely to approve for MSM and serodiscordant couples, perhaps dampening the public debate on these questions--but focusing the debate on the wider indication? 

PrEP: does risk compensation matter?

From today's meeting of the Antiviral Drugs Advisory Committee, which will advise FDA on whether to approve a new prevention indication for Truvada: Susan Buchbinder from the SF Dept of Public Health discusses the potential role of risk compensation in PrEP implementation.  (Risk compensation would occur if patients, perceiving PrEP to reduce their risk of HIV acquisition, start to engage in riskier behaviors and/or reduce their use of other protection methods such as condoms.  Clinical trials on PrEP have not found significant evidence of risk compensation, but can't rule out the possibility in real-world practice.)

Buchbinder notes that in terms of overall risk reduction, even partial PrEP efficacy would offset a fair amount of risk compensation--that is, it would take a lot more unprotected sex to eliminate the benefit of an intervention that reduces risk by, say, 60%.  She also draws an analogy to statins, a partially effective drug intervention used to reduce risk of cardiovascular diseases.  Whereas risk compensation is continually debated in the context of partially effective HIV risk reduction methods such male circumcision and PrEP, she notes, it is rarely discussed in the context of statins: doctors don't withhold statins based on the worry that patients will end up eating more cheeseburgers.

This analogy raises the question of whether the focus on risk compensation in HIV prevention has something to do with social norms: whereas eating an unhealthy diet is common in most groups, are the activities that increase HIV risk--unprotected sex, especially anal sex, and IV drug use--regarded in a way that makes the possibility of their increase seem disproportionately problematic?  Is the concern amplified by cultural taboos?