Continued follow-up of Phambili phase 2b randomized HIV-1 vaccine trial participants supports increased HIV-1 acquisition among vaccinated men

Zoe Moodie, Barbara Metch, Linda Gail Bekker, Gavin Churchyard, Maphoshane Nchabeleng, Koleka Mlisana, Fatima Laher, Surita Roux, Kathryn Mngadi, Craig Innes, Matsontso Mathebula, Mary Allen, Carter Bentley, Peter B. Gilbert, Michael Robertson, James Kublin, Lawrence Corey, Glenda E. Gray

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21 Citations (Scopus)

Abstract

Background. The Phase 2b double-blinded, randomized Phambili/HVTN 503 trial evaluated safety and efficacy of the MRK Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine vs placebo in sexually active HIV-1 seronegative participants in South Africa. Enrollment and vaccinations stopped and participants were unblinded but continued follow-up when the Step study evaluating the same vaccine in the Americas, Caribbean, and Australia was unblinded for nonefficacy. Final Phambili analyses found more HIV-1 infections amongst vaccine than placebo recipients, impelling the HVTN 503-S recall study. Methods. HVTN 503-S sought to enroll all 695 HIV-1 uninfected Phambili participants, provide HIV testing, risk reduction counseling, physical examination, risk behavior assessment and treatment assignment recall. After adding HVTN 503-S data, HIV-1 infection hazard ratios (HR vaccine vs. placebo) were estimated by Cox models. Results. Of the 695 eligible, 465 (67%) enrolled with 230 from the vaccine group and 235 from the placebo group. 38% of the 184 Phambili dropouts were enrolled. Enrollment did not differ by treatment group, gender, or baseline HSV-2. With the additional 1286 person years of 503-S follow-up, the estimated HR over Phambili and HVTN 503-S follow-up was 1.52 (95% CI 1.08-2.15, p = 0.02, 82 vaccine/54 placebo infections). The HR was significant for men (HR = 2.75, 95% CI 1.49, 5.06, p = 0.001) but not for women (HR = 1.12, 95% CI 0.73, 1.72, p = 0.62). Conclusion. The additional follow-up from HVTN 503-S supported the Phambili finding of increased HIV- 1 acquisition among vaccinated men and strengthened the evidence of lack of vaccine effect among women.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Original languageEnglish
Article numbere0137666
JournalPLoS ONE
Volume10
Issue number9
DOIs
Publication statusPublished - 14 Sep 2015

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