Pre-exposure prophylaxis for HIV prevention under review by Food and Drug Administration
Pre-exposure prophylaxis (PrEP) for HIV prevention has taken a giant step forward with a Food and Drug Administration (FDA) committee's recommendation for approval of a specific drug for such use.The FDA's Antiviral Drugs Advisory Committee voted for the use of once-daily oral Truvada (Gilead Sciences, Foster City, CA), in conjunction with condoms and other safer-sex measures, for HIV prevention in men who have sex with men, persons in discordant couples, and other individuals at risk for acquiring HIV through sexual activity. The vote came after a May 2012 presentation of scientific information on use of the drug for such purposes.
While the committee's recommendation is not an agency approval, it is seen as a "milestone in HIV prevention," according to a statement issued by the HIV Prevention Trials Network, an HIV/AIDS clinical trials research network. Truvada was approved by the FDA in 2004 for the treatment of HIV-1 infection. The agency has established a June 15, 2012, target review date for action on the drug's application for the new indication.
The advisory committee members voted 19-3 in favor of approval for Truvada for PrEP in men who have sex with men; 19-2 (with one abstaining) in support of use in HIV-uninfected partners in serodiscordant couples; and 12-8 (with two abstaining) in other individuals at risk for acquiring HIV through sexual activity.
Who supports move?
A group of 15 leading HIV/AIDS and health organizations has stated its support for FDA approval of the drug, a combination of emtricitabine and tenofovir disoproxil fumarate, as pre-exposure prophylaxis in preventing HIV infection in adult men and women. The advisory committee's recommendation brings the PrEP option "closer to a watershed for global HIV prevention efforts," said Mitchell Warren, executive director of AVAC, a New York City-based nonprofit advocacy group for biomedical HIV prevention research. AVAC is one of the 15 groups calling for approval of Truvada for PrEP use.
"PrEP, while not a panacea, will be an essential additional part to the world's success in ending AIDS," said Warren in a statement following the FDA panel vote. "For the millions of men and women who remain at risk for HIV worldwide, each new HIV prevention option offers additional hope that we will achieve the end of the epidemic."
The FDA panel reviewed numerous data sets from clinical trials, including results from the National Institutes of Health funded international iPrEx study; the University of Washington's Partners PrEP study conducted in Kenya and Uganda; the Centers for Disease Control and Prevention's TDF2 safety study conducted in Botswana; FHI 360's FEM-PrEP study conducted in Kenya, South Africa and Tanzania; and the NIH VOICE study conducted in Uganda, South Africa, and Zimbabwe.1-5
Research presented at the FDA committee meeting indicated that Truvada PrEP generally was safe and well-tolerated. No new safety issues were identified. Adverse events appeared to be balanced between active and control arms, the FDA noted in background material.6
Should Truvada be approved for PrEP use, clinicians making the decision should carefully weigh the individual patient's risks for acquiring HIV, their understanding of the importance of adherence to medication, and their potential for development of renal toxicity, which is a side effect of the combination drug, the FDA background information states.6 Education about PrEP and behavioral counseling are critically important, it notes. "Baseline evaluation of individuals should include HIV testing, assessment of renal function, serum phosphorous, and assessment for the presence of risk factors for development of renal or bone toxicities," the background material states. "Consideration should also be given to providing the individual with Vitamin D and calcium supplementation."
Periodic evaluation of the individual during PrEP administration should include regular HIV testing and monitoring for the development of renal dysfunction; DEXA scans prior to and periodically during treatment might be considered for some individuals, the background material states.6
Gilead Sciences has proposed dispensing a Truvada medication guide with each Truvada PrEP prescription, and it says it will implement voluntary training and education through a Truvada for PrEP educational program for healthcare providers.7 Two identified risks associated with using Truvada as PrEP — HIV acquisition and the development of drug resistance — will be addressed by these two initiatives, as well as the need for careful prescribing, adherence, and follow-up practices for individuals with chronic hepatitis B virus infection, who can experience acute liver disease complications if tenofovir and emtricitabine are not taken correctly or are stopped abruptly.7
CDC spearheads guidance
How should clinicians currently approach PrEP? The Centers for Disease Control and Prevention (CDC) is spearheading national efforts to develop formal Public Health Service guidelines for PrEP. Until those guidelines are available, CDC has developed interim guidance for clinicians electing to provide PrEP for HIV prevention among MSM. It also is drafting interim guidance for use in heterosexuals. Clinicians should consult the CDC web site, www.cdc.gov/hiv/prep, for the latest guidance.
Several projects are now looking at PrEP use in the United States. The Oakland-based California HIV/AIDS Research Program of the University of California has awarded grants totaling $11.8 million to three teams of investigators to test PrEP among high-risk HIV-uninfected people in California.
Two of the research teams will offer PrEP to some 700 high-risk uninfected men who have sex with men and to transgender women (male-to-female transgendered people) in Los Angeles, San Diego, and Long Beach over the next four years.
The scientists also will assess the implementation of testing and linkage to care plus treatment (TLC+), a strategy to locate, engage, and retain HIV-infected people in care and start them on HIV infection treatment. The TLC+ intervention will include some 3,000 people in Southern California.
The third research group will plan and pilot PrEP/TLC+ implementation strategies for young men who have sex with men of color in Oakland, Richmond, Berkeley, and other East Bay locations. According to project leaders, this initiative will be the largest PrEP/TLC+ demonstration project initiative in the United States and the first to test PrEP in the targeted Southern California communities.
George Lemp, DrPH, California HIV/AIDS Research Program director, said, "These studies will provide critical information on the implementation of PrEP and TLC+ strategies in California and will help guide state and national efforts to address the epidemic," [Contraceptive Technology Update sent an ebulletin May 11 to our subscribers about the FDA panel's recommendation. If you didn't receive the ebulletin, we don't have your email address. To receive future bulletins, contact customer service at (800) 688-2421 or email@example.com.]
- Grant RM, Lama JR, Anderson PL, et al; iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. NEJM 2010; 363(27):2,587-2,599.
- Baeten J, Donnell D, Ndase P; Partners PrEP Study Team. ARV PrEP for HIV-1 prevention among heterosexual men and women. Presented at the 19th Conference on Retroviruses and Opportunistic Infections. Seattle; March 2012.
- Thigpen MC, Kebaabetswe PM, Smith DK, et al. Daily oral antiretroviral use for the prevention of HIV infection in heterosexually active young adults in Botswana: results from the TDF2 study. Presented at the 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Rome, Italy; July 2011.
- Van Damme L, Corneli A, Ahmed K, et al. The FEM-PrEP trial of emtricitabine/tenofovir disoproxil fumarate (Truvada) among African women. Presented at the 19th Conference on Retroviruses and Opportunistic Infections. Seattle; March 2012.
- Celum CL. HIV preexposure prophylaxis: new data and potential use. Top Antivir Med 2011; 19(5):181-185.
- Food and Drug Administration. Background package for NDA 21-752/Supplement 30. Accessed at http://1.usa.gov/IS40N1.
- Horn T. Truvada receives PrEP approval recommendation. AIDSmeds; May 11, 2012. Accessed at http://bit.ly/JFkhnk.