Current HIV clinical trials
The 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.
The trial demonstrated that the vaccine regimen was safe and modestly effective in preventing HIV infection. The results show that the prime-boost combination lowered 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).
This study results, announced by the Army in 2009, showed that a preventive HIV vaccine is possible and is providing scientific direction to help guide future vaccine development and testing. Since then, MHRP researchers—in collaboration with partners worldwide—have made substantive progress in understanding what it will take to develop a more efficacious HIV vaccine.
Building on Success
In April, 2012 the New England Journal of Medicine 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 who subsequently became infected with HIV. The findings, published in September 2012 in Nature, reinforced that antibodies directed at the V1V2 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, ” noted Col. Jerome Kim, MHRP Principal Deputy Director and senior author on the study.
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% (95% CI 22–80)—through 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.
BMC Medical Research Methodology at the 35th Annual Conference of the .. — BMC Pediatrics
The conference will focus on issues such as design and analysis of clinical trials, methods in biostatistics and development of clinical prediction models.