FDA approves once-daily oral agent for HIV prevention in uninfected adults

July 17, 2012

FDA has approved once-daily oral emtricitabine and tenofovir disoproxil fumarate (Truvada, Gilead Sciences), in combination with safer sex practices, to reduce the risk of sexually acquired HIV-1 infection in adults at high risk.

FDA has approved once-daily oral emtricitabine and tenofovir disoproxil fumarate (Truvada, Gilead Sciences), in combination with safer sex practices, to reduce the risk of sexually acquired HIV-1 infection in adults at high risk.

This is the first agent to be approved for HIV prevention in uninfected adults, a strategy called pre-exposure prophylaxis (PrEP). As part of the approval, Gilead worked with the FDA to develop a Risk Evaluation and Mitigation Strategy (REMS) to help ensure safe use of emtricitabine and tenofovir disoproxil fumarate for PrEP as part of a comprehensive prevention strategy. Emtricitabine and tenofovir disoproxil fumarate was originally approved in 2004 in combination with other antiretroviral agents as a treatment of HIV-1 infection in adults and is currently the most-prescribed antiretroviral product in the United States.

It is estimated that 1.2 million Americans are currently living with HIV, and, despite the availability of existing prevention tools such as condoms, the incidence rate has remained steady over the past 2 decades with approximately 50,000 new infections occurring each year. Nearly one-quarter (23%) of new HIV cases occur among women, and more than half (61%) occur among men who have sex with men (MSM). In particular, young African American MSM bear a heavy burden of the epidemic, with new HIV cases among this group increasing by nearly 50% between 2006 and 2009.

Data supporting the approval of emtricitabine and tenofovir disoproxil fumarate for PrEP came primarily from 2 large placebo-controlled trials known as the Pre-Exposure Prophylaxis Initiative (iPrEx), sponsored by the US National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation, and Partners PrEP, sponsored by the University of Washington and funded by the Bill and Melinda Gates Foundation. The iPrEx and Partners PrEP trials found that emtricitabine and tenofovir disoproxil fumarate reduced the risk of acquiring HIV infection by 42% and 75%, respectively. Several other clinical studies also support the use of emtricitabine and tenofovir disoproxil fumarate for HIV risk reduction.

“This approval is a major milestone in our 30-year fight against AIDS,” said Robert M. Grant, MD, MPH, Betty Jean and Hiro Ogawa Endowed Investigator, Gladstone Institute of Virology and Immunology, University of California, San Francisco and lead investigator of the iPrEx trial. “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.”

Based on the iPrEx results, in January 2011, the Centers for Disease Control and Prevention (CDC) issued interim guidance on emtricitabine and tenofovir disoproxil fumarate as PrEP among high-risk adult MSM. CDC is currently developing formal US Public Health Service guidelines for the use of PrEP among both men and women, which will address procedures for HIV testing and health screening prior to PrEP initiation, as well as ongoing monitoring for cases of HIV infection that may occur despite PrEP use, possible drug resistance among those who become infected, side effects, and clinical toxicities.

“The data clearly demonstrate that Truvada as pre-exposure prophylaxis is effective at reducing the risk of HIV infection acquired through sexual exposure,” said Connie Celum, MD, MPH, professor of global health and medicine at the University of Washington and lead investigator of the Partners PrEP trial. “It is exciting to consider the potential impact of this new HIV prevention tool, which could contribute to significantly reducing new HIV infections as part of a combination HIV prevention strategy. Although the implementation of PrEP will bring challenges, they can be anticipated and systems developed to address these challenges. In particular, systems to provide comprehensive education and support to healthcare providers and people who use PrEP will be required to ensure appropriate and effective use of this potentially groundbreaking new HIV prevention intervention.”

As part of the REMS developed by Gilead and FDA to ensure safe use of emtricitabine and tenofovir disoproxil fumarate for PrEP, Gilead has developed FDA-approved materials to educate and inform healthcare providers and uninfected individuals about Truvada for PrEP. These materials highlight the importance of strict adherence to the dosing regimen, emphasize that emtricitabine and tenofovir disoproxil fumarate must be considered as only 1 part of a comprehensive prevention strategy to reduce the risk of HIV-1 infection. In addition, it should convey that emtricitabine and tenofovir disoproxil fumarate for PrEP should only be used in individuals who are confirmed HIV negative, and HIV-1 screening should be repeated at least every 3 months while taking emtricitabine and tenofovir disoproxil fumarate for PrEP. Truvada for PrEP should not be initiated when clinical signs or symptoms consistent with acute HIV-1 infection are present.

As a separate measure to support the safe use of emtricitabine and tenofovir disoproxil fumarate for PrEP, Gilead also 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 emtricitabine and tenofovir disoproxil fumarate for PrEP.

In all studies of emtricitabine and tenofovir disoproxil fumarate for PrEP, the most commonly reported side effects included headache, stomach discomfort, and weight loss. The incidence and types of side effects were consistent with Truvada’s safety and tolerability profile when used as an HIV treatment, which is supported by more than 4 million years of patient use. Overall, there have been nearly 9 million patient years of experience with tenofovir-containing regimens.

For more information on Truvada, click here.