HIV drugs can do a remarkable job of suppressing high viral loads to undetectable levels, but can they prevent that infection in the first place? Most people thought that they could in theory but there was no proof of that … until now.
Results from the Preexposure Prophylaxis Initiative ( iPrEx ) Trial found that drugs could reduce new infections by 43.8 percent in the high-risk men who have sex with men ( MSM ) and transgender persons in the study. It was published in the New England Journal of Medicine Nov. 23.
The $43.6-million trial enrolled 2,499 participants at 11 sites on four continents, including San Francisco and Boston in the United States. Despite the fact that MSM are much more likely to be infected with HIVthey are more than half of those infected in the US and in the broader epidemic of sub-Saharan Africa they are at least four times as likely as their heterosexual counterparts to be infected with the virusthis is the first large biochemical prevention study conducted in MSM.
Participants were randomized to receive once a day dose of either Truvada, a single pill containing the drugs emtricitabine and tenofovir, or placebo, essentially a sugar pill with no active ingredients. They also received counseling on HIV prevention at every meeting with the study team. The analysis was based on a median of 1.2 years on the drug.
Of the first 100 people to become infected with HIV, 64 were receiving placebo ( an annual infection rate of about 4 percent ) and 36 were on Truvada. The 43.8 percent rate of protection was no home run but within the same ballpark as the protection seen in other recent prevention trials; the vaginal microbicide trial of tenofovir gel in African women ( 39 percent ) and a vaccine trial in Thailand ( 31 percent ) .
Digging deeper, the researchers found that adherence was a very important part of the equation. The men who took at least half of their doses had 50.2 percent fewer infections; those who took at least 90 percent of their medication had 72.8 percent fewer infections. Even the best drugs will not work if people don't take them as they should.
Robert Grant, M.D., is a researcher at the Gladstone Institute at the University of California San Francisco and the principle investigator of the study. He said they asked participants to report how often they took their pills, but because people often are "optimistic" in their recall, and sometimes report what they think researchers want to hear, the study also tested for levels of the drug in the blood of those who became infected.
"No drug was detected in 91 percent; the other 9 percent had detectible levels inside blood cells that were very low. The absence of drug in the blood is probably due to people not taking the drug, which could explain all of the infections that did occur" in that group, Grant said.
The association between adherence and the level of protection was similar to what was seen in the microbicides trial. People who most closely used the product as intended had the best results. Cutting corners gave HIV an opportunity that it quickly exploited.
"The iPrEx study results are extreme important and provide strong evidence that PrEP [ preexposure prophylaxis ] can reduce HIV acquisition among a segment of society disproportionately affected by HIV/AIDS," said Anthony Fauci, MD, director of the NIH National Institute of Allergy and Infectious Diseases. It provided $27.8 million toward the study.
He emphasized that despite this good news, "correct and consistent use of condoms and a reduction in the number of sex partners still remain the most effective ways to protect yourself from HIV infection."
"This is great news," said Thomas J. Coates, Ph.D., a leading international HIV prevention researcher at the University of California Los Angeles David Geffen School of Medicine. "But if it would have been any lower, I would have been devastated."
University of Pittsburgh HIV prevention researcher Ronald Stall, Ph.D., called the results "very good news for gay men and other populations at high risk of HIV transmission." It also points to the continued need for better behavioral interventions to support adherence.
Gilead Sciences manufactures Truvada and supported the iPrEx study by providing all of the drugs used. The company said it "will be working with the appropriate regulatory agencies to determine if data from this study warrant inclusion in the prescribing information for Truvada."
While doctors can prescribe drugs for "off label" use that the FDA has not approved, and some already prescribe Truvada for prevention, health insurance companies generally only reimburse for the use indicated on the label of the drug.
Adding a prevention indication to the drug label likely will require additional trials in MSM and other populations, particularly with regard to preventing vaginal transmission of HIV. Some of those studies already are underway.
"The big conundrum right now is what does it mean for practice?" Coates said the response was not sufficiently great to signal immediate widespread adoption of this approach as a prevention intervention, particularly given issues of cost.
The retail price of the drug in the United States is about $14,000 a year, while the NIH pharmacy purchases it for about $5,000 a year, Fauci said.
In developing countries, generic versions of Truvada can be purchased for as little as 40 cents a day, according to Grant. However, those are the same places where more than half of the people already infected with HIV, who meet guidelines to begin treatment, cannot do so because of the cost. It is unlikely that public health officials will devote scarce resources to Truvada when a condom will do the same job much more cheaply.
Furthermore, an international survey of more than 5,000 participants, to be released next week by the Global Forum on MSM & HIV, found that more than half of MSM worldwide do not have access to basic HIV prevention and treatment services. Adding PrEP to the mix will be a challenge.
The paper "Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men" is freely available from the New England Journal of Medicine at http:// www.nejm.org/doi/full/10.1056/NEJMoa1011205.