More than 2 million
AIDS-related deaths occurred globally in 2008, and more than 33 million people are living with HIV/
AIDS. Despite promising advances in prevention, an estimated 2.7 million new
HIV infections occurred in that year, so that for every two patients placed on combination antiretroviral treatment, five people became infected. The pandemic poses a formidable challenge to the development, progress, and stability of global society 30 years after it was recognized. Experimental preventive HIV-1
vaccines have been administered to more than 44,000 human volunteers in more than 187 separate trials since 1987. Only five candidate
vaccine strategies have been advanced to efficacy testing. The recombinant
glycoprotein (rgp)120
subunit vaccines,
AIDSVAX B/B and
AIDSVAX B/E, and the Merck Adenovirus serotype (
Ad)5 viral-vector expressing HIV-1 Gag, Pol, and Nef failed to show a reduction in
infection rate or lowering of postinfection viral set point. Most recently, a phase III trial that tested a heterologous prime-boost
vaccine combination of
ALVAC-HIV vCP1521 and bivalent rgp120 (
AIDSVAX B/E) showed 31% efficacy in protection from
infection among community-risk Thai participants. A fifth efficacy trial testing
a DNA/recombinant(r) Ad5 prime-boost combination is currently under way. We review the clinical trials of
HIV vaccines that have provided insight into human immunogenicity or efficacy in preventing HIV-1
infection.