There’s huge news today in the results of a major drug trial for HIV prevention, but the news comes balanced with significant cautions and caveats. For the first time, researchers have shown that if men who are not infected with HIV take routine doses of AIDS treatment drugs, they can markedly reduce their risk of becoming infected.
Writing in the New England Journal of Medicine, a multi-national team show that, when HIV-negative sexually active men take the once-daily pill Truvada (actually a combination of two AIDS drugs, FTC and DTF), they reduce their risk of becoming infected with HIV by an average of 44 percent. Among men who took the pill diligently — proven in the trial not only by counting their remaining pills but by analyzing their blood for drug residue — the protection rose to 73 percent.
The finding is powerful evidence that it is possible to protect people who are at high risk of infection — even in very resource-poor settings — from acquiring HIV. The 2,499 men in six countries who participated in the study were chosen because they were very high risk: they had sex with other men, as gay men or as self-identified transgender women; they had multiple sexual partners (on average, 18 in the 3 months before the study began); two-thirds regularly had anal sex without condoms; and two-fifths regularly traded sex for drugs, food, shelter or money.
The trial they were recruited into divided the men into groups that received the actual drug or a placebo, and packaged the drugs with a suite of additional services: free condoms, coaching in how to prevent infection, STD testing, regular HIV tests, and short courses of drugd to prevent infection if they had sex that they thought might have exposed them to HIV. The men stayed in the trial for an average of 1.2 years, with the longest participation 2.8 years.
At the end of one year, 100 men in the trial had become infected: 36 of those taking Truvada and 64 of those on placebo.
When the researchers checked those who remained HIV-negative, they found something interesting: Only half of those who claimed to have taken all their pills had actually done so, as proved by analysis of their blood for the drugs’ chemical signature. That suggested that the drug was more protective than the 44 percent risk reduction suggested, and that very good compliance with such a drug regimen might be much more protective than the overall results showed.
That’s a potential success — and at the same time, it’s a pointer to such a regimen’s likely challenge if deployed in the real world. Adherence to the drug regimen turned out to be lower than the study design had predicted — and yet, it may have been as high as it was only because of the intensive attention that the participants received.
A thoughtful accompanying editorial raises just some of the important questions:
…What is the likelihood that such a regimen could be accomplished in an implementation program that lacks the intense reinforcement of adherence counseling provided in the context of a clinical trial? How can medication-use fatigue be mitigated over potentially many years of daily therapy? What are the potential long-term safety issues for healthy persons, as well as those with coexisting illnesses, such as diabetes or hypertension? What will the [trial] results mean for other populations with a lower risk of HIV acquisition? What would be the effect of open-label FTC–TDF use on the prophylactic use of condoms, on knowledge of HIV-infection status (both for subjects and their partners), and on the frequency of casual sex?
There’s another open question as well, something that AIDS researchers have fretted about since pre-exposure and post-exposure prophylaxis began to be talked about in the 1990s after the advent of powerful multi-drug cocktails changed the course of the epidemic. (I myself first wrote about these issues in 1997, but I can’t link to the story as it’s behind a stupid paywall.) We accept that incomplete treatment of an organism makes it more likely that the organism will evolve resistance to the treatment. If pre-exposure prophylaxis for HIV became common, would we run that risk for this virus as well?
The authors are careful to say that Truvada was chosen in part because it is not a great stimulator of resistance. And in the trial, only two cases of resistant virus developed, in men who received the active drug but turned out to have been infected before the trial started. That’s a very low rate — but these were unusual circumstances, with a great deal of energy expended on persuading the participants to adhere to their regimens. If this were deployed in the real world, would the resistance rates still be so low?
Prevention of HIV infection has been a dearly sought goal since the start of the epidemic almost 30 years and 40 million cases ago. For many years, the news has been consistently disappointing; it’s really only in the past 12 months that a few findings have started to be positive. So this trial result is important news, and is likely to be looked at as a way forward. It will be important to see whether the public health questions — about applicability, expense and especially unintended consequences such as resistance — get asked as well.
Grant RM et al. Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men. doi: 10.1056/NEJMoa1011205. (And detailed supplementary appendix.)
Michael NL. Oral Preexposure Prophylaxis for HIV — Another Arrow in the Quiver? doi: 10.1056/NEJMe1012929.
Web site for the iPrEx trial