First Preventative HIV Drug Leads to More Research and Debate

Author:  Michael Nagle
Institution:  American University
Date:  September 2012


The Food and Drug Administration approved the first drug for the prevention of HIV infection in July, although conditionally, requiring the manufacturer to run more tests. The AIDS Healthcare Foundation (AHF), the largest AIDS organization in the world, called this decision “reckless,” claiming these requirements are not enough to prevent drug-resistant strains from emerging.

“The FDA’s approval of Gilead’s Truvada as a form of HIV prevention today without any requirement for HIV testing is completely reckless and a move that will ultimately set back years of HIV prevention efforts,” said Michael Weinstein, AHF’s President, in a press release. He said the FDA has refused to meet with them to discuss these concerns. The FDA did not respond to a request for comment.

Truvada, made by Gilead Sciences, is a combination of two antiretroviral drugs and is already used in infected patients. As research has been published over the past few years, more doctors have been prescribing it off-label for prevention of HIV. When given to patients who are uninfected and high-risk, Truvada is part of a treatment called pre-exposure prophylaxis (PrEP).

“If an HIV-infected individual who did not know his or her HIV status was prescribed and used Truvada ... the outcome could be devastating, ultimately leading to drug resistance to an otherwise potentially life-saving AIDS treatment,” said Dr. Jorge Saavedra, Global Ambassador for AHF and former head of the Mexican National AIDS Program, in a press release. The FDA’s approval requires that a warning on every bottle of Truvada say it should only be prescribed to patients who are confirmed HIV negative, but the AHF sees this guideline as insufficient and believes a mandate would be better.

“The AIDS Healthcare Foundation has distinguished itself as an outlier,” said Mitchell Warren, Executive Director of the AIDs Vaccine Advocacy Coalition (AVAC). “It’s safe to say the AIDS community is solidly behind the decision that the FDA made this week. It is a historic decision. I’m not aware of anyone other than the AIDS Healthcare Foundation who thinks this is a bad decision.”

Since they began tracking PrEP research in 2004, AVAC has looked into many of the concerns AHF is raising. “The AIDs Healthcare Foundation is raising the right questions, but rather than wanting to progressively address them, they want to ignore the opportunity that PrEP presents,” Warren said. “And it’s a very real opportunity to provide some people with an additional prevention option that might save their lives.”

Tom Myers, AHF’s General Counsel, responded, saying that although AHF is in the minority, they are not alone.

“Given that AVAC is an information-based organization,” he said, “I’m surprised that it appears to be unaware of the contrary positions taken by the British HIV Association and the British Association for Sexual Health and HIV, the Chairman of the International Symposium on HIV & Emerging Infectious Diseases, the Lancet, articles in the American Journal of Public Health, and the members of the FDA Advisory Committee who voted against recommending approval of Truvada as PrEP, which vote was attended by Mr. Warren.”

In May, after an 11-hour meeting that included a public forum, the FDA Advisory Committee voted to suggest the FDA approve Truvada. The decision, which the FDA was not required to follow, was 19-3 and 19-2 in approving the drug for the high-risk groups studied and 12-8 in approving it for unspecified, other groups. Those opposed to approving the drug expressed concerns about drug-resistant HIV strains emerging.

A study published in the New England Journal of Medicine in July tested Truvada in 4,700 uninfected patients in heterosexual relationships with partners who have the virus. Among all patients given the drug,  eight were already infected, two of whom developed resistance. The iPrEx study, which enrolled a total of 2,499 men who have sex with men in 11 countries, saw another two infected patients develop drug resistance. In all cases, the infection was too recent to appear in the first HIV test, so they began taking the drug and did not know of their infected status until their next visits. The test measures antibody production and most people don’t start producing antibodies until 2-8 weeks after exposure, according to Centers for Disease Control.

“Ideally someone would have the rapid test, followed by another test within a few weeks, before going on to PrEP,” Warren said. “That’s something that providers do know how to manage.” Doctors can get results from a rapid test within 20 minutes in their office, but if a positive patient has not yet begun to produce measurable antibodies, they will appear negative. Physicians will be trained and educated on the risks under the Risk Evaluation and Mitigation Strategy coupled with the FDA’s approval of Truvada.

The FDA’s decision is conditional and requires Gilead to collect viral strains from people who become infected while taking the drug. They are also required to run studies to evaluate how failure to take the drug daily as prescribed may lead to infection and the development of viral drug resistance. The iPrEx study found that up to 10 percent of patients did not stick to the regimen and that taking it daily is essential to prevention of infection. Detectable levels of Truvada were found in the blood of 51 percent of a group that remained HIV-negative, but in only 9 percent of participants who became HIV infected. Upcoming studies, which were planned before the FDA’s announcement, will look at how to help patients adhere to the regimen.

“We’re investigating the use of cellphones and text messages to check in with people about their pill taking,” said Albert Liu, Ph.D, Director of HIV prevention and intervention studies with the San Francisco Department of Public Health. Liu worked on the San Francisco leg of iPrEx, which included counseling to help people implement the daily pill into their regimen.

"If we tell gay men that there is a magic pill that will protect them, fewer of them will use condoms and more of them will become infected,” says the AIDs Healthcare Foundation on their website “Gilead is irresponsibly seeking more profits based on a single study with dubious results." Multiple studies on Truvada have shown the opposite to be true, according to Liu. The iPrEx study found patients had less partners and less unprotected sex than they did before enrolling.

“It’s very paternalistic to assume how people will behave if they take a pill, or for us to decide who should get access to what,” Warren said. “To say we have potential hypothetical risks and not actually try to address the concern is ridiculous... PrEP is not just a pill. It is a program that includes [HIV] testing, counseling, condoms and a pill. That’s what the AIDS Healthcare Foundation and other people seem to forget.”

The AIDS Healthcare Foundation believes that Truvada has not been established as safe and effective “under real world conditions,” and calls for more research. “This is not an issue of paternalism or free choice,” Myers said.

AHF has been calling attention to the fact that among the entire study population, iPrEx only found a 44 percent reduction in infection. However, many patients in the study did not take Truvada daily as prescribed, or even at all. Researchers took blood tests to see if patients were actually taking it. Rates of infection were reduced by 92 percent in those with the drug in their blood.

This is more than enough to significantly slow the spread of HIV, according to Caitlin Mahon, who manages information for AVERT, an international charity that claims to run the most visited website about AIDs, based on pageviews. According to mathematical models, if “PrEP was used by 90 percent of high-risk people and was effective 90 percent of the time, potentially the spread of HIV infection could be reduced by more than 80 percent in a few years,” she said.

The iPrEx study continues and is now focusing on viral resistance and efficacy in patients who don’t take it as prescribed. Last week they published research which concluded failure to take Truvada daily does not significantly compromise the drug’s efficacy.

This science feature article was written under the guidance of JYI Science Writing Mentor Brooke Borel.