TY - JOUR
T1 - Continued follow-up of Phambili phase 2b randomized HIV-1 vaccine trial participants supports increased HIV-1 acquisition among vaccinated men
AU - Moodie, Zoe
AU - Metch, Barbara
AU - Bekker, Linda Gail
AU - Churchyard, Gavin
AU - Nchabeleng, Maphoshane
AU - Mlisana, Koleka
AU - Laher, Fatima
AU - Roux, Surita
AU - Mngadi, Kathryn
AU - Innes, Craig
AU - Mathebula, Matsontso
AU - Allen, Mary
AU - Bentley, Carter
AU - Gilbert, Peter B.
AU - Robertson, Michael
AU - Kublin, James
AU - Corey, Lawrence
AU - Gray, Glenda E.
N1 - Funding Information:
The authors have read the journal's policy and the authors of this manuscript have the following competing interests: MA is employed by the National Institute of Allergy and Infectious Diseases (NIAID), the study sponsor. All authors are current recipients of NIAID funding, and this publication is a result of activities funded by NIAID. MA was not involved with the process of funding these awards, nor in their administration or scientific aspects, and, in accordance with NIAID policies, is deferred from decisions regarding funding of coauthors for a requisite period. This study was also partly funded by Merck and Co Inc. Michael Robertson is an employee of and owns stock in Merck Research Laboratories. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
PY - 2015/9/14
Y1 - 2015/9/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84947474577&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0137666
DO - 10.1371/journal.pone.0137666
M3 - Article
C2 - 26368824
AN - SCOPUS:84947474577
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 9
M1 - e0137666
ER -
