The ALVAC/AIDSVAX prime-boost combination HIV vaccine demonstrated a small and only marginally significant protective effect in the Phase III RV144 clinical trial in Thailand. While detailed data did not live up to the initial hype, some researchers hailed the findings as proof-of-concept that a preventive HIV vaccine can work.
In September, the U.S. Military HIV Research Program (MHRP) announced that in an analysis of more than 16,000 study participants, those who received ALVAC/AIDSVAX had a 31% lower risk of HIV infection compared with placebo recipients. However, a closer look at the complete data, presented at the AIDS Vaccine 2009 conference in Paris and simultaneously published in the October 20, 2009, online edition of the New England Journal of Medicine, revealed less impressive results.
Overall, 56 vaccine recipients and 76 placebo recipients were newly infected with HIV during follow-up. In an intent-to-treat analysis, there was a trend toward a significant protective effect, with an efficacy of 26.4%; however, the P value (a standard statistical measure) of 0.08 did not reach the usual 0.05 cut-off for significance and the confidence interval was very wide, indicating considerable uncertainty about whether the results were due to chance alone.
In a modified intent-to-treat analysis that excluded seven people who were belatedly determined to have been already HIV-infected at study entry, vaccine efficacy was 31.2% -- the figure reported in September -- and this just reached the cut-off for statistical significance, with a P value of 0.04. But in a per-protocol or as-treated analysis of participants who received all vaccine doses as scheduled, efficacy fell to 26.2% and was no longer close to borderline significance (P = 0.16). Vaccination did not affect viral load levels or CD4 cell counts in participants who did become infected.
"Although the results show only a modest benefit, they offer insight for future research," the RV144 investigators concluded. For example, they plan to explore why ALVAC/AIDSVAX provided the greatest protective effect during the first year (about a 60% risk reduction), and why heterosexual participants at low or medium risk for HIV infection appeared to derive more benefit than high-risk participants such as gay men or injection drug users.
The Thai trial results were "the first signal of [HIV vaccine] efficacy, extremely modest though it might be," National Institute of Allergy and Infectious Diseases director Anthony Fauci said at a CROI plenary. In particular, the findings may offer insights about the correlates of protection, or what needs to happen for a vaccine to work.
Liz Highleyman (email@example.com) is a freelance medical writer based in San Francisco.
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