U.S. Department of Defense


Date of this Version



Lancet Infect Dis 2012; 12: 531–37; DOI:10.1016/S1473- 3099(12)70088-9


Background The Thai phase 3 HIV vaccine trial RV 144 showed modest effi cacy of a vaccine against HIV acquisition. Baseline variables of age, sex, marital status, and risk did not modify vaccine effi cacy. We did a post-hoc analysis of the trial’s data to investigate behavioural risk and effi cacy every 6 months after vaccination.

Methods RV 144 was a randomised, multicentre, double-blind, placebo-controlled effi cacy trial testing the combination of the HIV vaccines ALVAC-HIV (vCP1521) and AIDSVAX B/E to prevent HIV infection or reduce setpoint viral load. Male and female volunteers aged 18–30 years were recruited from the community. In this post-hoc analysis of the modifi ed intention-to-treat population (16 395 participants), HIV risk behaviour was assessed with a self-administered questionnaire at the time of initial vaccination in the trial and every 6 months thereafter for 3 years. We classifi ed participants’ behaviour as low, medium, or high risk. Both the acquisition endpoint and the early viral-load endpoint were examined for interactions with risk status over time and temporal eff ects after vaccination. Multiple proportional hazards regression models with treatment and time-varying risk covariates were analysed.

Findings Risk of acquisition of HIV was low in each risk group, but 9187 (58·2%) participants reported higher-risk behaviour at least once during the study. Participants classifi ed as high or increasing risk at least once during followup were compared with those who maintained low-risk or medium-risk behaviour as a time-varying covariate, and the interaction of risk status and acquisition effi cacy was signifi cant (p=0·01), with greater benefi t in low-risk individuals. Vaccine effi cacy seemed to peak early—cumulative vaccine effi cacy was estimated to be 60·5% (95% CI 22–80) through the 12 months after initial vaccination—and declined quickly. Vaccination did not seem to aff ect viral load in either early or late infections.

Interpretation Future HIV vaccine trials should recognise potential interactions between challenge intensity and risk heterogeneity in both population and treatment eff ects. The regimen tested in the RV 144 phase 3 trial might benefi t from extended immunisation schedules.

Funding US Army Medical Research and Materiel Command and Division of AIDS, National Institute of Allergy and Infectious Disease, National Institutes of Health.