Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection

Background. A vaccine is needed to prevent human immunodeficiency virus type 1 (HIV-1) infection. Methods. A double-blind, randomized trial of a recombinant HIV-1 envelope glycoprotein subunit (rgp120) vaccine was conducted among men who have sex with men and among women at high risk for heterosexual transmission of HIV-1. Volunteers received 7 injections of either vaccine or placebo (ratio, 2:1) over 30 months. The primary end point was HIV-1 seroconversion over 36 months. Results. A total of 5403 volunteers (5095 men and 308 women) were evaluated. The vaccine did not prevent HIV-1 acquisition: infection rates were 6.7% in 3598 vaccinees and 7.0% in 1805 placebo recipients; vaccine efficacy (VE) was estimated as 6% (95% confidence interval, -17% to 24%). There were no significant differences in viral loads, rates of antiretroviral-therapy initiation, or the genetic characteristics of the infecting HIV-1 strains between treatment arms. Exploratory subgroup analyses showed nonsignificant trends toward efficacy in preventing infection in the highest risk (VE, 43%; n = 247) and nonwhite (VE, 47%; n = 914) volunteers (P = .10, adjusted for multiple subgroup comparisons). Conclusions. There was no overall protective effect. The efficacy trends in subgroups may provide clues for the development of effective immunization approaches.