The U.S. Food and Drug Administration on Monday announced it has approved use of the AIDS drug Truvada for reducing the risk of HIV infection among uninfected people considered at high risk for contracting HIV through sexual contact.
The decision to allow Truvada to be taken daily in the form of a pill as part of a prevention regimen known as pre-exposure prophylaxis, or “PrEP,” has drawn mixed reactions among AIDS advocacy organizations, with most supporting the decision.
But others have raised strong objections, saying potentially harmful side effects of Truvada along with the risk of HIV infection through non-adherence to a rigid daily drug regimen, which in turn could lead to drug-resistant strains of HIV, far outweigh the benefits.
“Today’s approval marks an important milestone in our fight against HIV,” said FDA Commissioner Dr. Margaret Hamburg. “Every year, about 50,000 U.S. adults and adolescents are diagnosed with HIV infection, despite the availability of prevention methods and strategies to educate, test, and care for people living with the disease,” she said.
“New treatments as well as prevention methods are needed to fight the HIV epidemic in this country,” Hamburg said.
Truvada, which is manufactured by the pharmaceutical firm Gilead Sciences, was first approved in 2004 by the FDA for use as a treatment for HIV.
In announcing its approval for use as a prevention drug, the FDA pointed to two large placebo-controlled trials of the drug as a prophylaxis that were sponsored by the U.S. National Institutes of Health and the University of Washington.
One of the trials conducted in the U.S. and abroad evaluated the drug in 2,400 HIV-negative men or transgender women who have sex with men and who are prone to “high risk behavior,” such as inconsistent or no condom use during sex, according to a statement released by the FDA.
“Results showed Truvada was effective in reducing the risk of HIV infection by 42 percent compared with [a] placebo in this population,” the FDA statement says.
It says the second trial included 4,759 heterosexual couples where one partner was HIV-infected and the other was HIV negative. Truvada reduced the risk of becoming infected by 75 percent compared to participants taking a placebo, the FDA statement says.
Among those supporting the FDA decision to approve Truvada as a prevention drug is Project Inform, the San Francisco based HIV patient advocacy group that has closely observed prevention and treatment options for people with HIV and AIDS for more than 20 years.
“Project Inform is extremely pleased with a landmark decision by the FDA to approve the first biomedical HIV prevention product in the history of the epidemic,” the group said in a statement.
“Finally, after 30 years, HIV-negative individuals have a new way to protect themselves from becoming infected,” said Project Inform Director Dana Van Gorder. “While PrEP isn’t a tool that will be appropriate for broad use, we are thrilled to have a new option that could offer substantial benefit to those at highest risk for HIV, including gay and bisexual men and transgender women who struggle with consistent condom use, and in heterosexual women living in areas with high HIV rates whose partners refuse to use condoms,” Van Gorder said.
The AIDS Institute, a national AIDS advocacy group with offices in Washington, D.C. and Florida, and the Boston-based Fenway Health and its research arm Fenway Institute also issued statements supporting the FDA action.
Taking the opposite view is the Los Angeles based AIDS Healthcare Foundation, which provides HIV/AIDS treatment programs in the U.S. and in countries throughout the world, including Africa and Asia.
“My initial reaction is that this is a catastrophe for AIDS prevention in the U.S.,” said Michael Weinstein, AHF’s executive director.
Weinstein said global trial studies cited by the FDA involved constant monitoring and encouragement by organizers to ensure that participants adhered to their daily drug regimen as well as engaged in safer sex practices, such as condom use.
“The bottom line is that was under ideal conditions,” he said. “People were tested monthly. They were intensively counseled. They were paid to be in the study. And only about 50 percent took the drug.”
He predicted far fewer people “in the real world” would be compliant in taking their daily drug regimen, especially since the drug, as reported by Gilead Sciences, induces occasional side effects in healthy people such as headache, stomach discomfort and weight loss.
Weinstein said that in addition to opening the way for users to lower their guard and stop using condoms, even though the FDA approval calls for continued use of safer sex practices along with Truvada, the drug is highly dangerous for people who become HIV positive without knowing it.
In its published drug warnings, Gilead says use of Truvada alone is harmful to people with HIV unless they use it in combination with other antiretroviral drugs. Weinstein said he fears that people using Truvada as a prevention pill and become HIV positive after failing to take the drug every day could be at high risk – both for becoming ill and developing a drug resistant strain of HIV.
Dr. Debra Brinkrant, an FDA official who has monitored the Truvada studies, said an analysis of the trial studies showed that those who used Truvada used condoms more frequently and did not discontinue condom use.
“Everyone has to work together to make sure this works,” she said. “We must see that adherence is maintained. This is a first step to cut the infection rate,” a rate she said has not decreased in spite of years of other HIV prevention and education programs.
Justin Goforth, director of medical adherence and head of the Sexually Transmitted Disease Clinic at D.C.’s Whitman-Walker Health, said Whitman-Walker has already been prescribing Truvada as a prevention pill as part of a small study program. He said Whitman-Walker will likely expand the number of people it approves for use of the drug as a prevention medication now that the FDA has issued its approval.
“A lot of gay men are coming in and begging us to get this,” he said. “This is clearly not for everyone. The issue is finding the right people. They have to be people at high risk,” he said, adding that men who have sex with men who themselves or their partners have trouble being complaint with condom use, or those with multiple sex partners, would be among those considered for Truvada as a prevention pill.
Goforth acknowledged that the NIH sponsored trials of Truvada for men who have sex with men and transgender women had an adherence rate of about 50 percent. The fact that they were paid to be in the trials could have been responsible for the low adherence rate, with many choosing to join the program for the purpose of taking the money rather than the pills, Goforth said.
But he said Whitman-Walker has found through its limited Truvada trial program for HIV negative people that those seeking out the drug have followed the daily pill regimen.
“I feel people who come forward now to take this have a greater incentive for compliance,” he said.
And Goforth pointed to studies showing that Truvada’s effectiveness in preventing HIV infection is greater than 90 percent among those who take the pill every day.