- Category: HIV Prevention
- Published on Monday, 16 July 2012 00:00
- Written by Liz Highleyman
On July 16, 2012, the U.S. Food and Drug Administration (FDA) approved Truvada -- Gilead Sciences' tenofovir/emtricitabine combination pill -- for pre-exposure prophylaxis (PrEP) to prevent sexual transmission of HIV.
"Today’s approval marks an important milestone in our fight against HIV," said FDA Commissioner 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. New treatments as well as prevention methods are needed to fight the HIV epidemic in this country."
The FDA's approval came 2 months ahead of its September 14 deadline. A decision had originally been expected by June 15 -- about a month after the agency's Antiviral Drugs Advisory Committee recommended approval -- but was delayed to allow more time for development of a Risk Evaluation and Management Strategy (REMS) that includes atraining and education program for providers.
"The REMS for Truvada for the PrEP indication is aimed at educating health care professionals and uninfected individuals to help ensure its safe use for this indication without placing an unnecessary burden on health care professionals and patients," said Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, in an agency press release.
Gilead requested approval for the expanded indication in December 2011 based on a growing body of evidence showing that tenofovir/emtricitabine can lower the risk of HIV acquisition if taken every day.
The iPrEx study of gay and bisexual men and a small number of transgender women showed that once-daily Truvada PrEP reduced the incidence of new infections by 42% overall, 73% among people with reported good adherence, and 92% among those with measurable drug levels in their blood.
"This approval is a major milestone in our 30-year fight against AIDS," iPrEx lead investigator Robert Grant said in a press release issued by Gilead. "The use of PrEP alongside routine HIV testing gives us a tremendous opportunity to reduce the rate of new HIV infections in this country and around the world."
The Partners PrEP and TDF2 studies -- first presented at last summer's International AIDS Society meeting in Rome and published just last week in the New England Journal of Medicine -- showed that daily tenofovir, with or without emtricitabine, reduced the incidence of new infections by 60% to 75% for heterosexual men and women.
"PrEP offers a new prevention tool for those most at risk for HIV, and should be provided in the context of other prevention strategies, including HIV and sexually transmitted infection testing, condoms, and with adherence support," said Partners PrEP principal investigator Connie Celum after the Antiviral Drugs Advisory Committee's May 10 vote. "To turn the tide on the HIV epidemic in the US and globally, we need to be guided by evidence in developing our approach to HIV prevention."
PrEP data have not been unanimous, however. The Fem-PrEP study of Truvada for heterosexual women (also published in NEJM last week) was halted early because it was unable to demonstrate a preventive effect, as was an arm of the VOICE trial testing oral tenofovir alone.
While Truvada PrEP appears highly effective -- at least for selected, high-risk populations that use it as part of a comprehensive prevention strategy that also includes condoms and risk-reduction counseling -- some have raised concerns regarding the difficulty of ensuring good adherence, possible long-term side effects (especially bone and kidney toxicity), drug resistance, and cost and access issues.
To address the risk of resistance if people who are already HIV infected take tenofovir/emtricitabine without other antiretrovirals, individuals seeking PrEP must receive a confirmed negative HIV test before starting Truvada and every 3 months thereafter.
As a condition of approval, Gilead will be required to collect viral isolates from people who contract HIV while taking Truvada to perform drug resistance testing and must collect data on pregnancy outcomes among women who become pregnant while taking Truvada PrEP.
In addition, the company will conduct a study to evaluate drug adherence and its relationship to adverse events, risk of seroconversion, and resistance among people who become infected. Gilead also said it will provide drug utilization data to better understand who is using PrEP, and will develop an adherence questionnaire to help clinicians identify individuals at risk for poor adherence.
Gilead indicated that it will provide vouchers for free HIV testing and condoms, an opt-in service for regular reminders about HIV testing, and subsidized HIV resistance testing for any individual who becomes HIV positive while taking Truvada for PrEP.
Overall, advocates and public health officials applauded the FDA decision.
"Finally, after 30 years, HIV negative individuals have a new way to protect themselves from becoming infected," said Project Inform executive 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."
"Today’s decision by the FDA heralds a new era in HIV prevention -- one with great promise for expanded access to HIV testing and prevention counseling and support," concurred San Francisco AIDS Foundation CEO Neil Giuliano. "The approval paves the way for increased work with the federal government and Gilead Sciences to ensure they realize the incredible impact they can now have to get Truvada to the communities that stand to benefit most, especially gay men and people of color."
The National Institute of Allergy and Infectious Diseases is preparing to launch PrEP demonstration projects in conjunction with local health departments. The first projects, in San Francisco and Miami, are expected to start in August, according to NIAID spokesperson Tasheema Prince.
"PrEP is an important and welcome step forward as momentum builds for making serious headway against HIV infection," said Judith Aberg, chair of the HIV Medicine Association.
Aberg cautioned, however, that implementation of PrEP "must not contribute to HIV-related health care disparities," noting that the low-income and minority populations most heavily affected by HIV infection are less likely to be engaged in health care and are more likely to be uninsured or rely on Medicaid coverage.
"We know the drugs work remarkably well if you take them consistently, and when combined with other prevention methods, including condoms," stated Project Inform director of research advocacy David Evans. "Now we must learn how best to offer this potentially very effective tool to individuals who need it most in real-world settings."
U.S. Food and Drug Administration. FDA Approves First Drug for Reducing the Risk of Sexually Acquired HIV Infection. Press release. July 16, 2012.
Gilead Sciences. U.S. Food and Drug Administration Approves Gilead’s Truvada for Reducing the Risk of Acquiring HIV. Press release. July 16, 2012.
HIV Medicine Association. HIVMA Supports FDA PrEP Decision, Urges Attention to Health Disparities. Press release. July 16, 2012.
Project Inform Praises FDAs Approval of HIV Prevention Pill. Press release. July 16, 2012.
San Francisco AIDS Foundation. Important New HIV Prevention Tool Wins FDA Approval. Press release. July 16, 2012.
AIDS Healthcare Fundation. AHF: FDA 'Reckless' in Approving Gilead's Controversial HIV 'Prevention' Pill. Press release. July 16, 2012