In November when researchers revealed positive results from the first large-scale trial of anti-HIV drugs to prevent sexual transmission of the virus, a barrage of questions immediately surfaced about how best to use so-called Pre-Exposure Prophylaxis (PrEP). Today, the U.S. Centers for Disease Control and Prevention (CDC) issued the first recommendations to healthcare providers about PrEP. Although the "interim guidance" has few surprises and is only a stopgap until the U.S. Public Health Service issues more formal recommendations, clinicians are welcoming the input. "It is an important step in the development of recommendations," says Robert Grant, a virologist with the J. Gladstone Institutes at the University of California, San Francisco (UCSF), who headed the positive PrEP trial.
The study, reported online 23 November in The New England Journal of Medicine, found that daily use of two anti-HIV drugs combined into a single pill called Truvada reduced the risk of transmission in uninfected men and transgender women who have sex with men by 44%. The efficacy jumped to 73% in a subset of participants who reported taking their pills each day at least 90% of the time, indicating that prevention was tightly tied to adherence to the trial protocol. The findings received widespread media reports and were praised by researchers around the world as an important advance for the failure-weary HIV-prevention field.
Grant and his co-workers stressed from the outset that the results apply only to this population, and the CDC's interim guidance repeats that caveat. It also recommends that clinicians carefully test patients for HIV infection before prescribing Truvada as a preventive and then follow up with tests every 2 to 3 months. CDC suggests the same daily dosing, counseling, and condom provision as used in the study and says prescriptions should be for 90 days only, which would give clinicians a formal way to confirm periodically that their patients are still HIV negative. (In HIV-infected people, Truvada is used only in combination with other antiretrovirals to prevent the emergence of drug-resistant strains of the virus.)
CDC says it issued the interim guidance because of concerns that "unsafe and potentially less effective PrEP practices could develop" before the final recommendations are issued, as Truvada is already a licensed drug for HIV treatment and clinicians already are prescribing its off-label use as a preventive. Specifically, CDC said it wanted to dissuade clinicians from prescribing other anti-HIV drugs as PrEP, using a dosing schedule other than the one proven to work in the study, providing prescriptions without counseling and condoms, and not properly testing and monitoring patients for HIV infection.
The guidance says it will take "several months" for PHS to issue more thorough recommendations, as it now is gathering "expert input and public comment."
Davey Smith, an HIV/AIDS clinician at UC San Diego, says a still-unresolved question is cost. "The main holdup is going to be who's going to pay for it," says Smith. "It's also the lowest socioeconomic gay men who have a burden already. They're the neediest of the needy, and they're the ones who don't have access to healthcare. I don't think we've been very good at thinking about the other side of the coin."