It's been quite the year (plus a month) for HIV prevention research.
That glimmer of hope from the Thai vaccine trial. The striking effect of HIV-treatment as prevention. The positive results of the CAPRISA vaginal microbicide study, which were presented to rapturous applause this summer in Vienna.
And today, the iPrEx study is published, which shows that giving TDF/FTC to HIV-negative, high-risk men who have sex with men (MSM) reduces their risk of acquiring HIV by 44%. It's the first efficacy study of pre-exposure prophylaxis (PrEP) and will undoubtedly generate plenty of discussion.
For a detailed scientific analysis of the trial, two HIV prevention experts have already provided their commentary, Nelson Michael in NEJM and Raphy Landovitz in Journal Watch AIDS Clinical Care. I highly recommend both.
But every HIV specialist/Infectious Disease doctor will have thoughts on this important study, so in no particular order, here are mine:
- A few doctors (mostly those with patient panels with large numbers of MSM) anecdotally have already been prescribing PrEP, at least to a limited extent. If this practice expands, will insurance cover it? Like virtually everything else in our patchwork healthcare "system", I suspect this will vary widely from plan to plan and from state to state. And you can be sure that for the time being this will not be covered under the state-based AIDS Drug Assistance Programs (ADAPs).
- Aside from those providers, what other clinicians will actually prescribe PrEP? ID docs? Primary care providers? Many HIV specialists don't follow HIV-negative patients; providers who work in clinics that focus on treatment of sexually transmitted infections generally don't follow patients longitudinally; and non-HIV specialists have little familiarity with antiretrovirals.
- Would intermittent PrEP with TDF/FTC work just as well as continuous therapy? How intermittent? Again, anecdotally, this appears to be how most clinicians who have been prescribing PrEP have been using it.
- The intervention clearly worked in preventing HIV infection -- at least in those who took it. In fact, if you believe the pharmocology sub-group analysis, compliance was pretty lousy, with detectable drug levels found in only 9% of those acquiring HIV and 51% of those remaining HIV negative. Since this was in a research study setting, where compliance is usually better than in clinical practice, I'm not optimistic that the highest risk patients -- some of whom have significant drug-dependency and psychiatric disease -- are going to do very well with this.
- No drug is 100% safe, and the burden of proof for safety is greater when something is used as prevention rather than treatment. How safe does it have to be? I would say a good goal would be comparable safety to a widely adopted vaccine, a very high bar indeed.
- Two stylistic oddballs in the study: How does "iPrEx" stand for "Preexposure Prophylaxis Initiative"? What's with the funky capitalization scheme? An iPrEx sounds like a gizmo you plug into an iPhone. And why was coformulated tenofovir-emtricitabine abbreviated "FTC-TDF", when virtually every other mention of this product in the HIV universe does it in the other direction (i.e., TDF-FTC)?
Weird spelling notwithstanding, iPrEx is the first of several studies of PrEP, and its publication is a landmark event. The study continues with all subjects now receiving TDF/FTC (or FTC-TDF, grrr); hence there are more data to come -- not only from iPrEx but from the multiple other ongoing HIV prevention studies.
In fact, this timeline of HIV prevention research suggests that the next few years could, amazingly, be even more exciting than this past one.
Paul Sax is Clinical Director of Infectious Diseases at Brigham and Women's Hospital. His blog HIV and ID Observations is part of Journal Watch, where he is Editor-in-Chief of Journal Watch AIDS Clinical Care.