Background Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. Methods In nine countries, we enrolled 1763 couples in which one partner was HIV-1–positive and the other was HIV-1–negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1–infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1–related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1–negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death. Results As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P = 0.01). Conclusions The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy.

BACKGROUND-Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition.

Background The impact of HIV pre-exposure prophylaxis (PrEP) depends on uptake, adherence, and sexual practices. Methods Men and transgender women who have sex with men (MSM/TGW) previously enrolled in PrEP trials were enrolled in a 72 week open label extension (iPrEx OLE). Drug concentrations were measured in plasma and dried blood spots (DBS) in seroconverters and a random sample of seronegatives. Findings 1603 HIV uninfected persons were enrolled, of whom 76% received PrEP. PrEP uptake was higher among those reporting condomless receptive anal intercourse (ncRAI; P=0.003) and having serological evidence of herpes (P=0.03). Among those receiving PrEP, HIV incidence was 1.8/100PY, which was 49% (95% CI: −1 to 74%) lower than among those who concurrently did not choose PrEP after adjusting for sexual behavior, and 53% (95% CI: 26 to 70%) lower than in the placebo arm of the prior randomized phase (3.9/100PY). Among those receiving PrEP, HIV incidence was 4.7/100PY if drug was not detected in DBS, 2.3/100PY if drug concentrations indicated use of less than 2 tablets per week, 0.6/100PY for use of 2 to 3 tablets per week, and 0/100PY for use of 4 or more tablets per week (P<0.0001). PrEP drug concentrations were higher among people with older age, more schooling, ncRAI, more sexual partners, trans-identification, and a history of syphilis or herpes. Interpretation PrEP uptake was high when made available free of charge by experienced providers. PrEP impact is increased by greater uptake and adherence during periods of higher risk; disengagement after initial use is common. DBS drug concentrations are strongly correlated with PrEP’s protective benefit.