Human immunodeficiency virus vaccine trials

Abstract

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.

Figure 1.

Global clinical AIDS vaccine development. Depicted are three distinct, but interrelated, spheres of activity placed along a timeline. RV144 follow-up is ongoing, and seeks to identify a correlate of immune protection by interrogating RV144 samples or samples generated by follow-up studies. Exploratory research activities will include adaptive design clinical trials, which aim to rapidly identify next generation products that should proceed to efficacy testing. Product development activities seek to extend the RV144 proof of concept by studying pox-protein prime-boost strategies in high-risk populations from Africa and Thailand with different routes of exposure in pursuit of licensure to realize rapid public health benefit.