The ALVAC/gp120 + MF59 vaccines in the HIV Vaccine Trials Network (HVTN) 702 efficacy trial did not prevent human immunodeficiency virus-1 (HIV-1) acquisition. Vaccine-matched immunological endpoints that were correlates of HIV-1 acquisition risk in RV144 were measured in HVTN 702 and evaluated as correlates of HIV-1 acquisition.

Among 1893 HVTN 702 female vaccinees, 60 HIV-1–seropositive cases and 60 matched seronegative noncases were sampled. HIV-specific CD4⁺ T-cell and binding antibody responses were measured 2 weeks after fourth and fifth immunizations. Cox proportional hazards models assessed prespecified responses as predictors of HIV-1 acquisition.

The HVTN 702 Env-specific CD4⁺ T-cell response rate was significantly higher than in RV144 (63% vs 40%, P = .03) with significantly lower IgG binding antibody response rate and magnitude to 1086.C V1V2 (67% vs 100%, P < .001; P_mag < .001). Although no significant univariate associations were observed between any T-cell or binding antibody response and HIV-1 acquisition, significant interactions were observed (multiplicity-adjusted P ≤.03). Among vaccinees with high IgG A244 V1V2 binding antibody responses, vaccine-matched CD4⁺ T-cell endpoints associated with decreased HIV-1 acquisition (estimated hazard ratios = 0.40–0.49 per 1-SD increase in CD4⁺ T-cell endpoint).

HVTN 702 and RV144 had distinct immunogenicity profiles. However, both identified significant correlations (univariate or interaction) for IgG V1V2 and polyfunctional CD4⁺ T cells with HIV-1 acquisition.

Clinical Trials Registration . NCT02968849.