Continued Follow-Up of Phambili Phase 2b Randomized HIV-1 Vaccine Trial Participants Supports Increased HIV-1 Acquisition among Vaccinated Men

• Published in: PloS one Vol. 10; no. 9; p. e0137666
• Main Authors: Moodie, Zoe, Metch, Barbara, Bekker, Linda-Gail, Churchyard, Gavin, Nchabeleng, Maphoshane, Mlisana, Koleka, Laher, Fatima, Roux, Surita, Mngadi, Kathryn, Innes, Craig, Mathebula, Matsontso, Allen, Mary, Bentley, Carter, Gilbert, Peter B, Robertson, Michael, Kublin, James, Corey, Lawrence, Gray, Glenda E
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.09.2015; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; AIDS Vaccines - administration & dosage; AIDS Vaccines - adverse effects; AIDS Vaccines - immunology; Double-Blind Method; Female; Follow-Up Studies; Health risks; HIV; HIV Infections - epidemiology; HIV Infections - immunology; HIV Infections - prevention & control; Human immunodeficiency virus; Humans; Immunization; Infections; Laboratories; Male; Men; Proportional Hazards Models; Randomization; Recall; Risk Factors; Risk reduction; Risk taking; Sexually transmitted diseases; South Africa; STD; Treatment Outcome; Tutu, Desmond; Vaccines; Womens health; South Africa; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0137666

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 non-efficacy. Final Phambili analyses found more HIV-1 infections amongst vaccine than placebo recipients, impelling the HVTN 503-S recall study. 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. 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). 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. clinicaltrials.gov NCT00413725 SA National Health Research Database DOH-27-0207-1539.