The U.S. Food and Drug Administration (FDA) announced today that it has approved the drug Truvada for daily use to reduce the risk of HIV infection in uninfected adults at high risk of becoming infected. Truvada, taken daily, is being approved for pre-exposure prophylaxis (PrEP) in combination with safer-sex practices.
Dr. Debra Birnkrant, director of the division of antiviral products at the FDA's Center for Drug Evaluation and Research (CDER), warned on a conference call with reporters that the drug would have to be used in combination with safer-sex practices, plus regular counseling and HIV testing.
Truvada has been on the market since 2004, used to treat HIV-infected individuals as part of a daily regimen. Its component parts, tenofovir and emtricitabine, have been available since 2001 and 2003, respectively. In 2012, the FDA granted an expedited review of pharmaceutical giant Gilead's application to market Truvada as a once-a-day drug as part of PrEP.
In two clinical trials, daily use of Truvada was shown to reduce the risk of HIV infection by 42 percent among HIV-negative gay and bisexual men and transgender women, and by 75 percent among serodiscordant heterosexual couples, where one partner is infected with HIV and the other is not. According to Birnkrant, adherence rates to the full regimen, including testing, counseling and safer-sex practices, were about 30 percent in the first group and 80 to 90 percent in the second group.
Asked whether the approval of the drug would lead to individuals engaging in riskier sex practices, Birnkrant said the trial data showed that condom use among participants increased over time. As for known complications commonly associated with taking Truvada, including decreases in kidney function and bone marrow density, Birnkrant said the study showed such problems were mild and reversible.
Birnkrant said the FDA was hoping a daily regimen of Truvada, along with safer-sex practices, would decrease the number of new infections. To ensure the safety of individuals who take Trvuada as part of PrEP, the FDA has added language to the boxed warning on the drug's label and also approved a Risk Evaluation and Mitigation Strategy (REMS) designed to minimize the risk of acquiring HIV and developing resistant forms of the virus.
The REMS offers guidance for health care providers so they can determine whether to prescribe Truvada for HIV-negative patients.
In response to the announcement, the National Minority AIDS Council (NMAC) hailed the Truvada approval as an ''historic step'' in fighting HIV/AIDS. But Moises Agosto, NMAC's director of treatment, education, adherence and mobilization, cautioned that the treatment was ''by no means a panacea and is only effective when used in conjunction with traditional prevention and risk-reduction strategies, such as condom use.''
Agosto also clarified that Truvada as PrEP should only be prescribed to certain groups of people considered at high risk of infection, including serodiscordant couples, sex workers and gay men with multiple partners, who are willing to adhere to a daily regimen of medication.
''In recent years, there have been a number of promising developments in biomedical interventions – from treatment to prevention and pre-exposure prophylaxis to microbicides and vaccine research,'' Agosto said in an NMAC statement. ''Coupled with the reforms included in the Patient Protection and Affordable Care Act as well as the National HIV/AIDS Strategy, we are in a position for the first time in over three decades to finally end the epidemic. Today's decision is another important step in that goal.''
But the AIDS Healthcare Foundation (AHF) blasted the FDA's decision to approve Truvada for daily use as part of PrEP, calling the FDA's actions ''negligence bordering the equivalence of malpractice which will sadly result in new infections, drug resistance and serious side effects among many, many people.''
AHF took exception to what it sees as a lack of required HIV testing and a failure of the FDA to acknowledge another study showing a key component of Truvada is associated with significant risk of kidney damage and disease.
''The FDA'a 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,'' Michael Weinstein, AHF's president, said in a press release following the FDA announcement. ''From the beginning, we believe there was a rush to judgment by government officials and others in favor of such approval despite decidedly mixed studies offered in support. And while FDA recommends a negative HIV test prior to use of Truvada as PrEP … it in no way actually requires HIV testing in any manner – just strengthening of the 'boxed warning' on Gilead's packaging.''
Regarding the HIV-testing requirement, Weinstein said in a conference call with reporters that the approval of Truvada would place a large burden on doctors and health care providers, since, in practice, prescriptions would be refilled by pharmacists who would check with doctors to verify the prescription, but would only recommend, not require, HIV testing results in order to obtain the drug.
Weinstein also noted that in one of the FDA studies, there was a 42 percent effectiveness rate among people who were paid for their role in the study, a number that he suggested might drop if people engaged in riskier behaviors or did not adhere to their daily regimen. Furthermore, 50 percent of participants had no trace of the medication in their blood, Weinstein said, indicating an apparent lack of adherence.
Weinstein also alleged that the announcement of Truvada as a once-a-day pill to prevent HIV infection was timed to be a big revelation ahead of the XIX International AIDS Conference, occurring in D.C. July 22 to 27.
''This is a typical quick fix,'' Weinstein said. ''Pop a pill instead of doing the hard work.''
What would be more effective, Weinstein argued, is a campaign to distribute condoms, reach out to high-risk groups such as single men who have sex with men and sexually active people of color, identify those who are infected through testing and get them into treatment to reduce their risk of passing on the virus. Weinstein noted that AHF plans to distribute more than 20 million condoms in 2012 to help combat the epidemic.
Greater challenges, according to Weinstein, are that half of newly infected people don't know their status, along with a failure by society to adequately address testing, safe sex and comprehensive sex education.
''Most countries that have brought down the rate of HIV infection are those that are willing to talk about it,'' Weinstein said.
In response to AHF's claims, an FDA spokeswoman said that AHF's information was inaccurate, countering that testing was required and should be done every three months. She also released the text of new warning:
''TRUVADA used for a PrEP indication must only be prescribed to individuals confirmed to be HIV-negative immediately prior to initial use and periodically during use. Drug-resistant HIV-1 variants have been identified with the use of TRUVADA for a PrEP indication following undetected acute HIV-1 infection. Do not initiate TRUVADA for a PrEP indication if signs or symptoms of acute HIV infection are present unless negative infection status is confirmed.''
Ron Simmons, president and CEO of Us Helping Us, a local organization working to provide support services to black men infected with HIV/AIDS, responded to the news by saying he can't envision any doctor prescribing Truvada as part of PrEP and not requiring an HIV test, as it could serve as grounds for legal action. But he also rejected suggestions that approving the drug would cause MSM (men who have sex with men) to be less adherent or engage in riskier sexual behavior.
''That's going to be something we'll have to address when the time comes,'' he said. ''We can't naturally assume that MSM will be less adherent.''
Simmons said he has some reservations about prescribing a drug that has some degree of toxicity to people who are HIV-negative. But he also said more research was needed, particularly follow-up studies in order to see if dosage or frequency can be reduced.
Simmons said the biggest challenge his organization would face, particularly among black gay men, would be the distrust by the black community toward the U.S. medical establishment. He added that some black ministers have already come out in opposition to PrEP.
Simmons said that Us Helping Us has a lot of work to do to convince people with insurance of the benefit of taking Truvada as PrEP, and to gain access to the treatment for lower-income individuals. That latter group, he noted, would not have access to care or to preventative services free of charge until 2014, and only if the Affordable Care Act is implemented.
Justin Goforth, director of the medical adherence unit at local community health center Whitman-Walker Health, said he has heard arguments that approving Truvada will lead to greater risk—taking behaviors, but is skeptical of those claims, pointing out that once people are engaged in care, data shows their risk-taking behavior decreases.
As far as resistance to Truvada, Goforth said that can only occur if an individual has HIV, meaning they would have to seroconvert, or become HIV-positive, while taking Truvada as PrEP. If strategies for prevention are effectively implemented, he explained, individuals would remain negative. The small percentage of people who would seroconvert and be at risk for resistance would be nullified, at least from a public health standpoint, he said.
Taking care to acknowledge that data on these various factors as practiced outside of a clinical setting is not yet available, Goforth pointed out that many participants in the FDA study were not in the United States, but rather from countries with fewer resources. Therefore, the finding that 50 percent of study participants didn't take the medicine would not be shocking, as they would continue to get paid so long as they claimed they were taking the medicine.
By contrast, he said, in real-life practice, people who actively seek out PrEP will not be motivated by money, but will be seeking medical treatment willingly and will likely be paying a co-pay for the drug, which would reasonably push them to adhere more strictly to the daily regimen.
Goforth also said that multiple prevention techniques are essential to avoiding infection by HIV/AIDS, which is why he sees Truvada for PrEP as ''another tool in the toolbox.'' For example, he said, one's risk of transmitting or acquiring HIV lessens by combining prevention strategies, such as using condoms, having a positive partner in a serodiscordant couple receive treatment to achieve viral suppression, and having a negative partner take Truvada as part of PrEP.
Goforth also noted that PrEP is reserved for individuals deemed at very high risk of becoming infected with HIV, such as drug users, sex workers and people with multiple partners. But he also said it could be an ideal strategy for people at risk due to an imbalance in the ''power dynamic'' of a relationship, such as battered or abused women or younger gay men, particularly those of color, who are not in a position to negotiate sex with older partners upon whom they may be financially or emotionally reliant.
''That's enormous,'' he said. ''Because if you're in a situation where you know your partner isn't going to use a condom, now you have a choice.''