Prevention of HIV-1 infection with early antiretroviral therapy.

Abstract (PubMed)

Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. 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 or recurrent bacterial pneumonia, and other AIDS-defining illnesses or death. We observed 39 HIV-1 transmissions, 28 of which were virologically linked to the infected partner. Of these, only 1 occurred in the early-therapy group and 27 in the delayed-therapy group, for a 96% reduction in linked HIV-1 transmission (hazard ratio with early therapy, 0.04; 95% confidence interval [CI], 0.01 to 0.27; P<0.001). Early therapy was also associated with reductions in clinical events: 17 events in the early-therapy group versus 34 in the delayed-therapy group (hazard ratio, 0.41; 95% CI, 0.23 to 0.73; P=0.003). Antiretroviral therapy had both a protective effect on the HIV-1-negative partner and a clinical benefit for the HIV-1-infected partner.