Biomedical strategies to prevent sexual transmission of human immunodeficiency virus (HIV) remain limited.1 In animal models, preexposure prophylaxis with tenofovir disoproxil fumarate (TDF) or with the combination of TDF and emtricitabine (TDF–FTC) can prevent infections with HIV or hybrid simian–human immunodeficiency virus after vaginal or rectal challenge.2,3 In humans, daily preexposure prophylaxis with TDF–FTC has been shown to reduce transmission of HIV by 44% among men who have sex with men4; however, the findings from studies in heterosexual populations have been mixed.5-8
Botswana has the world's second highest prevalence of HIV infection, estimated in 2008 to be 17.6% overall and approximately 40% among adults 30 to 44 years of age. 9 Although Botswana was among the first African countries to introduce HIV prevention programs focused on male circumcision, prevention of mother-to-child transmission, and voluntary HIV counseling and testing, there is a need for additional prevention strategies to better control the generalized epidemic in this country. In this context, we conducted the TDF2 study to evaluate whether prophylaxis with daily oral TDF–FTC could prevent HIV infection among sexually active heterosexual adults.