Yesterday, the U.S. Food and Drug Administration approved Truvada (emtricitabine/tenofovir disoproxil fumarate), the first drug approved 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, taken daily, is to be used for pre-exposure prophylaxis (PrEP) in combination with safer sex practices to reduce the risk of sexually-acquired HIV infection in adults at high risk.
The FDA previously approved Truvada to be used in combination with
other antiretroviral agents for the treatment of HIV-infected adults and
children 12 years or older.
As part of PrEP, HIV-uninfected individuals who are at high risk will
take Truvada daily to lower their chances of becoming infected with HIV
should they be exposed to the virus. A PrEP indication means Truvada is
approved for use as part of a comprehensive
HIV prevention strategy that includes other prevention methods, such as
safe sex practices, risk reduction counseling, and regular HIV testing.
"Today’s approval marks an important milestone in our fight against
HIV," said FDA Commissioner Margaret A. Hamburg, M.D. "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."
As a part of this action, the FDA is strengthening Truvada’s 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. The drug is
contraindicated for PrEP in individuals with unknown or positive HIV
status. The FDA strongly recommends against such use.
Truvada for PrEP is being approved with a Risk Evaluation and
Mitigation Strategy (REMS) to minimize the risk to uninfected
individuals of acquiring HIV infection and to reduce the risk of
development of resistant HIV-1 variants. The central component of
this REMS is a training and education program to assist prescribers in
counseling 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
importance of adhering to the recommended dosing regimen and
understanding the serious risks of 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," said
Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation
and Research.
Truvada’s 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 included 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, Truvada’s manufacturer, Gilead Sciences,
Inc., is required to collect viral isolates from individuals who acquire
HIV while taking Truvada and to 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 drug adherence and its 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.