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Risk Behaviour and Time as Covariates for Efficacy of the HIV Vaccine Regimen ALVAC-HIV (vCP1521) and AIDSVAX B/E: A Post-Hoc Analysis of the Thai Phase 3 Efficacy Trial RV 144


Journal Article

Robb, M.L.; Rerks-Ngarm, S.; Nitayaphan, S.; Pitisuttithum, P.; Kaewkungwal, J.; Kunasol, P.; Khamboonruang, C.; Thongcharoen, P.; Morgan, P.; Benenson, M.; Paris, R.M.; Chiu, J.; Adams, E.; Francis, D.; , ; Stablein, D.; Michael, N.; Kim, J.H.

Lancet Inf Dis




Adolescent; Adult; AIDS Vaccines/therapeutic; Female; HIV Infections/epidemiology/prevention/control; Homosexuality Male; Humans; Intravenous/epidemiology; Kaplan-Meier; Male; Questionnaires; Risk-Taking; Statistics-Nonparametric; Substance Abuse

BACKGROUND: The Thai phase 3 HIV vaccine trial RV 144 showed modest efficacy of a vaccine against HIV acquisition. Baseline variables of age, sex, marital status, and risk did not modify vaccine efficacy. We did a post-hoc analysis of the trial's data to investigate behavioural risk and efficacy every 6 months after vaccination. METHODS: RV 144 was a randomised, multicentre, double-blind, placebo-controlled efficacy 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 modified 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 classified 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 effects 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 classified as high or increasing risk at least once during follow-up 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 efficacy was significant (p=0·01), with greater benefit in low-risk individuals. 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–and declined quickly. Vaccination did not seem to affect 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 effects. The regimen tested in the RV 144 phase 3 trial might benefit from extended immunisation schedules.

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