Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention
of human immunodeficiency virus (HIV) infection in some trials but not in others.
In this randomized, double-blind, placebo-controlled trial, we assigned 2120 HIV-negative
women in Kenya, South Africa, and Tanzania to receive either a combination of tenofovir
disoproxil fumarate and emtricitabine (TDF-FTC) or placebo once daily. The primary
objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition
and to evaluate safety.
HIV infections occurred in 33 women in the TDF-FTC group (incidence rate, 4.7 per
100 person-years) and in 35 in the placebo group (incidence rate, 5.0 per 100 person-years),
for an estimated hazard ratio in the TDF-FTC group of 0.94 (95% confidence interval,
0.59 to 1.52; P=0.81). The proportions of women with nausea, vomiting, or elevated
alanine aminotransferase levels were significantly higher in the TDF-FTC group (P=0.04,
P<0.001, and P=0.03, respectively). Rates of drug discontinuation because of hepatic
or renal abnormalities were higher in the TDF-FTC group (4.7%) than in the placebo
group (3.0%, P=0.051). Less than 40% of the HIV-uninfected women in the TDF-FTC group
had evidence of recent pill use at visits that were matched to the HIV-infection window
for women with seroconversion. The study was stopped early, on April 18, 2011, because
of lack of efficacy.
Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and
was associated with increased rates of side effects, as compared with placebo. Despite
substantial counseling efforts, drug adherence appeared to be low. (Supported by the
U.S. Agency for International Development and others; FEM-PrEP ClinicalTrials.gov
number, NCT00625404.).