Analysis of the HIV Vaccine Trials Network 702 Phase 2b-3 HIV-1 Vaccine Trial in South Africa Assessing RV144 Antibody and T-Cell Correlates of HIV-1 Acquisition Risk.

Journal Article (Clinical Trial, Phase III;Journal Article)

BACKGROUND: 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. METHODS: 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. RESULTS: 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; Pmag < .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). CONCLUSIONS: 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.

Full Text

Duke Authors

Cited Authors

  • Moodie, Z; Dintwe, O; Sawant, S; Grove, D; Huang, Y; Janes, H; Heptinstall, J; Omar, FL; Cohen, K; De Rosa, SC; Zhang, L; Yates, NL; Sarzotti-Kelsoe, M; Seaton, KE; Laher, F; Bekker, LG; Malahleha, M; Innes, C; Kassim, S; Naicker, N; Govender, V; Sebe, M; Singh, N; Kotze, P; Lazarus, E; Nchabeleng, M; Ward, AM; Brumskine, W; Dubula, T; Randhawa, AK; Grunenberg, N; Hural, J; Kee, JJ; Benkeser, D; Jin, Y; Carpp, LN; Allen, M; D'Souza, P; Tartaglia, J; DiazGranados, CA; Koutsoukos, M; Gilbert, PB; Kublin, JG; Corey, L; Andersen-Nissen, E; Gray, GE; Tomaras, GD; McElrath, MJ

Published Date

  • August 24, 2022

Published In

Volume / Issue

  • 226 / 2

Start / End Page

  • 246 - 257

PubMed ID

  • 35758878

Electronic International Standard Serial Number (EISSN)

  • 1537-6613

Digital Object Identifier (DOI)

  • 10.1093/infdis/jiac260

Language

  • eng

Conference Location

  • United States