A Game Change
As the Food and Drug Administration weighs approval of the off-label use of Truvada for HIV-negative individuals, we look at the arguments being made by those on both sides of the debate.
Dr. Lisa Sterman has been writing prescriptions for Truvada—a little blue pill that packs the punch of two anti-HIV medications, emtricitabine and tenofovir—to her patients, 80 percent of whom are gay men, for years.
But not all of her patients getting prescriptions for the antiretrovirals are, in fact, HIV positive. Nearly a dozen are high-risk HIV-negative individuals taking the drug for its preventive qualities.
Sterman, a physician, researcher and board member of the San Francisco AIDS Foundation, is one of a growing number in the medical field using Truvada as a way to prevent high-risk patients from contracting HIV.
From serodiscordant couples—couples where one partner is HIV negative and the other HIV positive—to at-risk gay men, Sterman advocates prescribing the drug for preventive uses.
“Given the fact that we can’t completely prevent HIV with traditional efforts like abstinence, condoms and testing, we need a more radical step for patients who are at high risk,” she says.
Every year, there are approximately 50,000 new HIV infections in the U.S., more than 50 percent of which are men who have sex with men, according to the Centers for Disease Control.
Sterman contends it’s time to think outside the box to defeat the epidemic.
The practice, called pre-exposure prophylaxis, or PrEP for short, has been the subject of several clinical trials involving heterosexual men and women, serodiscordant couples and high-risk gay men and is currently being considered for FDA approval. (At press time, the FDA’s Antiviral Drugs Advisory Committee recommended approval, with the FDA expected to issue its decision in August.)
During the trials, research subjects took Truvada every day—no other retroviral drugs have been tested to date—to maintain a certain amount in their bloodstream. They were also given condoms, risk-reduction counseling and regular HIV testing as part of an overall prevention program.
In one 2010 study called iPrEx, nearly 2,500 high-risk men who have sex with men from across six countries—including the U.S., Thailand, Brazil and South Africa—decreased their chances of contracting HIV by an average of 44 percent and up to 73 percent for those who reported compliance 90 percent of the time.
Researchers admit PrEP is not the silver-bullet cure for HIV/AIDS, stressing the continued importance of regular testing, condom use and, above all else, compliance. As far as compliance goes, there are serious concerns about the development of drug resistance as a result of patients not taking the drug regularly, though none of the noncompliant subjects in the trials developed such a condition.
The theoretical problem goes something like this: If someone is using Truvada as a PrEP but only sporadically—like using it as protection during a drunken, debaucherous weekend instead of condoms—and he was unknowingly exposed to HIV, he could actually develop a resistance to anti-HIV medications.
Not only would this make an entire class of drugs unavailable to that individual, the patient could then pass the drug-resistant strain on to others, effectively erasing
the medical advances made over the past two decades.
“I think we need more data on that,” says Sterman, “The bottom line is if you
don’t get infected, then you can’t become resistant.”
Sterman explains there’s no way to test this hypothetical situation in a clinical setting because of ethical concerns; you’d basically have to instruct a group of PrEP users to have sex with HIV-positive individuals. But if a client did develop drug resistance to one class of anti-HIV medications, she insists it’s not the big deal it would’ve been years ago.
“That is not the end of the world anymore,” she says, explaining that there are many other anti-HIV drugs. “If you do a cost–benefit analysis of the number of infections we may prevent with this drug versus the number of drug-resistant cases we might see, I think we win in terms of prevention.”
For some, though, the idea of using Truvada to prevent HIV infections is a bitter pill to swallow.
Michael Weinstein, president of the AIDS Healthcare Foundation, the largest HIV/AIDS healthcare provider in the United States, has serious doubts about the real-world applicability of the Truvada trials, the results of which he says weren’t even that great.
“The studies were done under ideal circumstances, meaning people were paid to be in the study, they were tested monthly, they were counseled intensively, and still only 18 percent of the people in the study took it every day,” he says, predicting that the 44 percent decreased infection rate will only come down in the real world.
Weinstein’s not alone. The British HIV Association, the British Association for Sexual Health and HIV, and French doctor Alain Lafeuillade, the chairman of the International Symposium on HIV and Emerging Infectious Diseases, have all come out against the use of Truvada as a PrEP.
Weinstein says he doubts that a healthy person would choose to take a daily drug and still use condoms, adding, “You’d really have to be paranoid about your pants falling down to wear both a belt and suspenders.
“I just cannot understand why you’d take a heavy-duty drug like this if you were wearing condoms,” he says, worrying that the safe-sex culture developed in the ’90s could be impacted by the widespread use of Truvada.
Sterman agrees. “If we say, ‘Just use Truvada,’ are we kind of condoning unsafe sex? I think that’s risky. We need to recognize the importance of making adult decisions and making those decisions in a clearheaded manner, in terms of not being on drugs and alcohol when you make them.”
Sterman also insists PrEP should not be seen as the first line of defense against the global pandemic. It’s only one weapon in an arsenal, all of which are needed to create a generation free of HIV/AIDS.
Weinstein says the two conventional methods of fighting the epidemic—condoms, which have a 95 percent rate of effectiveness when used properly, and treating HIV-positive individuals with anti-HIV drugs, which has a 96 percent rate of effectiveness—are the best ways to fight the epidemic. He worries PrEP could cause infection rates to go up, drug resistance to increase and the health of otherwise healthy men to be impacted negatively.
“If the first standard is to do no harm, [PrEP] could do a great deal of harm,” Weinstein says. “There are serious side effects, which are necessary if the person is HIV positive. But if you’re talking about giving this to healthy young men, it can cause kidney damage and bone loss, etc.”
The Truvada website lists diarrhea, nausea, headache, fatigue, kidney decline and failure and inflammation of the pancreas as potential side effects of taking the daily drug.
Sterman says she hasn’t seen many side effects firsthand. “My patients really don’t complain about much,” she says. “This drug is pretty clean in terms of side effects.”
She did say, though, that if she had a patient with pre-existing kidney problems, she’d take extra steps to regularly test kidney function, given the potential damage the drugs can cause.
Another issue raised by PrEP opponents is the fact that there are thousands of HIV-positive individuals currently on waiting lists for Truvada in cash-strapped states. Opening the drug up to a whole new customer base—those who don’t even “need” it—would spread resources even thinner.
“That’s immoral,” Weinstein says. “We’re going to spend millions to give HIV-negative men medications while there are waiting lists of people who are already HIV positive who are not receiving medication.”
A major obstacle to many HIV-positive patients currently is that a prescription for Truvada can cost up to $1,000 per month.
“The AIDS assistance programs in [some] other states are really scary,” says Sterman. “That’s up to each state’s budget to determine how their HIV assistance programs work. But I know that Gilead is committed to making this drug available to the people who need it.”
Sterman says that if FDA approved, Truvada’s manufacturer, Gilead Sciences, will most likely provide patient assistance in the form of a patient co-pay card and that the rest would most likely be funded by insurance companies and state-funded AIDS programs. Weinstein, however, suggests Gilead’s motives had much more to do with the company’s bottom line: “The patent for tenofovir, the leading drug in this combination, expires in five years.”
He also says the FDA doesn’t work independently from the pharmaceutical industry.
Ultimately, Weinstein thinks the amount of damage caused by the FDA’s approval of PrEP would depend on whether the government agency requires an initial HIV-negative test—and subsequent monthly tests—for someone to get a prescription for Truvada.
“If it’s allowed to be used the way Viagra is used, where you go online and find a doctor for hire who sells it, I think it’ll just become another party drug. That could have disastrous consequences.”
Even beyond its “party drug” uses in connection with unnecessarily risky encounters, Weinstein suggests the situation brings up a much larger issue regarding who is calling the shots in the gay community.
“At one time, the gay male community had a lot of influence on how we were treated. The drug companies and the government were not in charge,” he says. “Through our advocacy, we determined what was best for us. Unfortunately, that’s been drastically eroded.”
But Weinstein is not ready to back down. “Advocacy does work, and I’m naïve enough to believe that right prevails in the end.”