Modeling the impact of RV144-like vaccines on HIV transmission

Abstract

Some 30 years after the public first became aware of AIDS, the need for a safe, effective, and affordable HIV vaccine remains compelling [1]. To date, the road to an HIV vaccine has been rocky, marked by the well-publicized failures of the first two candidates to reach large population trials. The first, a recombinant gp120 AIDSVAX® B/E vaccine, proved ineffective [2, 3]. The second, a Merck recombinant adenovirus 5 gag/pol/nef HIV-1 vaccine targeting cell-mediated immunity in the STEP trial, actually increased the risk of HIV acquisition among vaccinees relative to placebo recipients [4]. Then, just as vaccine developers were returning to their drawing boards [5], the roller-coaster swung up again. On 20 October 2009, results of RV144 – a large, long duration, expensive (~120 million US$), community Phase III trial in Thailand evaluating a combination of two vaccines, ALVAC® HIV vaccine (a 4-dose prime) and the aforementioned AIDSVAX® B/E vaccine (a 2-dose boost) – were announced at the AIDS Vaccine 2009 Conference in Paris, France. There were 51 infections in 26,507 vaccinated person-years versus 74 in 26,478 unvaccinated person-years (p=0.04). Excluding 7 trial participants who were infected before vaccination, this prime-boost combination reduced the risk of HIV infection by 31.2% (95% CI, 1.1 to 51.2) overall compared to placebo [6].