July 16, 2012
On July 16, 2012, the Food and Drug Administration approved Truvada (a fixed dose combination of emtricitabine/tenofovir disoproxil fumarate) to reduce the risk of HIV infection in uninfected individuals who are at high risk of HIV infection and who may engage in sexual activity with HIV-infected partners.Truvada is to be used for pre-exposure prophylaxis (PrEP) in combination with safer sex practices to prevent sexually-acquired HIV infection in adults at high risk. Truvada is the first drug approved for this indication.
Truvada for PrEP is meant to be used as part of a comprehensive HIV prevention plan that includes risk reduction counseling consistent and correct condom use, regular HIV testing, and screening for and treatment of other sexually-transmitted infections. Truvada is not a substitute for safer sex practices
FDA previously approved Truvada (August, 2004) to be used in combination with other antiretroviral agents for the treatment of HIV-infected adults and children 12 years or older.
As a part of this action, FDA is strengthening Truvadas Boxed Warning to alert health care professionals and uninfected individuals that Truvada for PrEP must only be used by individuals who are confirmed to be HIV-negative prior to prescribing the drug and at least every three months during use to reduce the risk of development of resistant HIV-1 variants. The drug is contraindicated for PrEP in individuals with unknown or positive HIV status.
Truvada for PrEP is being approved with a Risk Evaluation and Mitigation Strategy (REMS). The central component of this REMS is a prescriber training and education program to assist prescribers in counseling and managing individuals who are taking or considering Truvada for PrEP. The training and education program will not restrict distribution of Truvada but will provide information about the important elements of a comprehensive HIV prevention strategy, the importance of adhering to the recommended daily dosing regimen, the serious risks of taking Truvada for PrEP if already infected with the virus or becoming infected with HIV while taking Truvada for the PrEP indication.
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 who use Truvada for treating HIV infection.
Truvadas safety and efficacy for PrEP were demonstrated in two large, randomized, double-blind, placebo-controlled clinical trials. The iPrEx trial evaluated Truvada in 2,499 HIV-negative men or transgender women who have sex with men and with evidence of high risk behavior for HIV infection, such as inconsistent or no condom use during sex with a partner of positive or unknown HIV status, a high number of sex partners, and exchange of sex for commodities. Results showed Truvada was effective in reducing the risk of HIV infection by 42 percent compared with placebo in this population. Efficacy was strongly correlated with drug adherence in this trial.
The Partners PrEP trial was conducted in 4,758 heterosexual couples where one partner was HIV-infected and the other was not (serodiscordant couples). The trial evaluated the efficacy and safety of Truvada and tenofovir versus placebo in preventing HIV infection in the uninfected male or female partner. Results showed Truvada reduced the risk of becoming infected by 75 percent compared with placebo.
No new side effects were identified in the clinical trials evaluating Truvada for the PrEP indication. The most common side effects reported with Truvada include diarrhea, nausea, abdominal pain, headache, and weight loss. Serious adverse events in general, as well as those specifically related to kidney or bone toxicity, were uncommon.
As a condition of approval, Truvadas manufacturer, Gilead Sciences, Inc., is required to collect viral isolates from individuals who acquire HIV while taking Truvada and evaluate these isolates for the presence of resistance. Additionally, the company is required to collect data on pregnancy outcomes for women who become pregnant while taking Truvada for PrEP and to conduct a trial to evaluate levels of drug adherence and their relationship to adverse events, risk of seroconversion, and resistance development in seroconverters. Gilead has committed to provide national drug utilization data in order to better characterize individuals who utilize Truvada for a PrEP indication and to develop an adherence questionnaire that will assist prescribers in identifying individuals at risk for low compliance.
Gilead Sciences, Inc. is based in Foster City, CA.
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