The Army-led Thai HIV vaccine efficacy trial, known as RV144, tested the “prime-boost” combination of two vaccines: ALVAC® HIV vaccine (the prime) and AIDSVAX® B/E vaccine (the boost). The vaccine combination was based on HIV strains that commonly circulate in Thailand.
RV144 and its follow-on trials allowed researchers to discover correlates of risk, provided targets for optimizing vaccine boosting, and provides a critical comparison for more recent HIV vaccine candidate trials.
The trial demonstrated that the prime-boost vaccine regimen was safe and modestly effective in preventing HIV infection, lowering the rate of HIV infection by 31.2 percent compared to placebo based on the modified intent-to-treat (mITT) population (n=51 vs. n=74, respectively; p=0.04). It is the only HIV vaccine trial to date to demonstrate efficacy in preventing HIV infection. Study results, announced by the Army in 2009 and published in the New England Journal of Medicine, showed that a preventive HIV vaccine is possible, revitalizing the research field and providing hope for millions.
The landmark trial launched MHRP's global reputation in HIV research and opened the door to dozens of collaborations around the world. The Thai trial continues to provide scientific direction to help guide vaccine development and testing. MHRP researchers and worldwide partners have made substantive progress in understanding what it will take to develop a more efficacious HIV vaccine. RV144 and its follow-on trials allowed researchers to discover correlates of risk and provided targets for optimizing vaccine formulation and regimens.
The V1/V2 Target
In April 2012, the New England Journal of Medicine (NEJM) published a paper co-authored by MHRP scientists that detailed clues to why the vaccine tested in the RV144 trial protected some volunteers. This unprecedented collaboration, led by researchers at Duke University and MHRP, brought together investigators from around the world to study those who became infected compared to those who did not. One finding was that immunoglobulin G antibodies that bind to the V1/V2 region of HIV’s envelope protein correlated with lower infection rates among those who were vaccinated.
Next, scientists examined whether those vaccine-induced antibody responses selectively blocked certain HIV variants. They examined HIV genome sequences from 110 volunteers who participated in RV144 and subsequently became infected with HIV. The findings, published in September 2012 in Nature, reinforced that antibodies directed at the V1/V2 region reduced the risk of infection. Taken together the work suggests that the Env-V2 region could be a critical target for future HIV vaccines.
In the May 2012 issue of The Lancet Infectious Diseases, MHRP researchers reported that vaccine efficacy seemed to peak early—cumulative vaccine efficacy was estimated to be 60.5 percent (95 percent CI 22–80)—in the 12 months after initial vaccination, after which it declined quickly. This early, high protective immune response suggests an additional boost or other augmentation of immune response would improve efficacy.
RV144 is generating a wealth of scientific data through secondary studies with collaborators around the globe. Follow-up studies are providing insights about possible strategies to improve strength and duration of immune response to the RV144 regimen.
The RV144 study was sponsored by the U.S. Army and conducted by the Thailand Ministry of Public Health. MHRP provided overall project leadership, and the Armed Forces Research Institute of Medical Sciences (AFRIMS) helped execute the trial. The study was made possible by an international collaboration involving numerous partners from the Thai and U.S. governments, private companies, non-profit organizations and more than 16,000 volunteers. It was supported by a cooperative agreement with the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
The RV144 Trial
A Phase III Trial of Aventis Pasteur Live Recombinant ALVAC-HIV(R) (vCP1521) Priming with VaxGen gp120 B/E (AIDSVAX(R) B/E) Boosting in HIV-uninfected Thai Adults