December 15, 2014
I admit that I was not a PrEP fanboy when it was first pitched. An HIV provider of a certain age, I was brought up on a latex-rich diet of condoms and dental dams. A pill to prevent HIV, in my view, negated the barrier -- tore it down and stamped on it. It seemed reckless.
My thinking about PrEP has evolved as its value has become more evident through both clinical research findings and experiences as a health care provider and educator. As my patients brought with them uninfected partners asking about PrEP, or talked about partners they met who insisted on unprotected sex, it became clearer to me that there is a need for an HIV prevention method that does not rely on barriers. I got it.
This year the U.S. Centers for Disease Control and Prevention (CDC) got it, too, and issued rather thoughtful recommendations for the use of PrEP for HIV prevention. The CDC guidance -- issued as a clinical practice guideline with a clinical providers' supplement -- is a nice how-to, geared to a nonspecialist readership, and is intended to raise awareness and acceptance of PrEP by providers.
On the heels of this official recommendation came new data that explain the real-world use of PrEP. For a while, the throbbing heart of research that supported PrEP was the iPrEx trial, a randomized, controlled study that found a significant reduction in the rate of incident HIV among high-risk men who have sex with men (MSM) and transgender women who were assigned to tenofovir/emtricitabine (Truvada) PrEP, as compared to a placebo. But efficacy, of course, was very dependent on adherence and raised concerns that in a real-world setting, suboptimal adherence would lead to transmission and even drug resistance.
An open-label study extension, iPrEx OLE, helps to address the "how much is enough" question. Measuring levels of tenofovir diphosphate in dried blood spots from the participants, the study team was able to calculate the approximate number of times a week the drug was taken and then look at incident HIV by adherence category.
For those taking four or more tablets per week, there were no incident infections. While a true protective threshold for tenofovir/emtricitabine cannot be firmly established by this study alone, the results demonstrate some forgiveness in adherence with overall substantial benefit even when doses were regularly missed.
Interestingly, those at greatest risk by virtue of certain behaviors -- such as unprotected receptive anal sex, known HIV-infected partner, and multiple sex partners -- were more likely to have high levels of tenofovir diphosphate than those with less risk, and thus presumably had less motivation to adhere.
Adding to the PrEP rally was the IPERGAY trial, which undoubtedly stands for something inoffensive in French. The intervention in this randomized trial among high-risk MSM of peri-coital PrEP consisted of four tablets of tenofovir/emtricitabine or placebo (two 2 to 24 hours before sex, a second dose 24 hours later, and a last one 24 hours after that). The study was stopped early when a significant difference in HIV incidence favoring the active drug arm was detected. Again, here we see a dosing strategy other than daily PrEP as an effective strategy for prevention.
Lastly, there is the pride-invoking PROUD study. This U.K. trial of high-risk MSM randomized to daily PrEP versus deferral of PrEP was also stopped and the control arm offered PrEP after an interim analysis found significant protection afforded by the active drug.
Overall, this post-iPrEx research has cemented the fact that PrEP works for MSM. Other studies showing efficacy of PrEP in injection drug users and women are also convincing. Now, we have to convince our primary care providers to join those of us in the HIV care community to prescribe this important intervention.
What are some other top clinical developments of 2014? Read more of Dr. Wohl's picks.
David Alain Wohl, M.D., is an associate professor of medicine in the Division of Infectious Diseases at the University of North Carolina and site leader of the University of North Carolina AIDS Clinical Trials Unit at Chapel Hill.
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