title: Continued Follow-Up of Phambili Phase 2b Randomized HIV-1 Vaccine Trial Participants Supports Increased HIV-1 Acquisition among Vaccinated Men.
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 non-efficacy. 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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov NCT00413725 SA National Health Research Database DOH-27-0207-1539.
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Moodie
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Barbara
authors.initials: B
authors.lastname: Metch
authors.affiliation: Desmond Tutu HIV Foundation, University of Cape Town, Cape Town, South Africa.
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.affiliation: Aurum Institute for Health Research, Johannesburg, South Africa; School of Public Health, University of Witwatersrand, Johannesburg, South Africa; London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Gavin
authors.initials: G
authors.lastname: Churchyard
authors.affiliation: Mecru Clinical Research Unit, Sefako Makgatho Health Sciences University, Pretoria, South Africa.
authors.forename: Maphoshane
authors.initials: M
authors.lastname: Nchabeleng
authors.affiliation: School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal and National Health Laboratory Service, Durban, South Africa.
authors.forename: Koleka
authors.initials: K
authors.lastname: Mlisana
authors.affiliation: Perinatal HIV Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
authors.forename: Fatima
authors.initials: F
authors.lastname: Laher
authors.affiliation: Desmond Tutu HIV Foundation, University of Cape Town, Cape Town, South Africa.
authors.forename: Surita
authors.initials: S
authors.lastname: Roux
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal and National Health Laboratory Service, Durban, South Africa.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Mngadi
authors.affiliation: Aurum Institute Clinical Research Site, Klerksdorp, South Africa.
authors.forename: Craig
authors.initials: C
authors.lastname: Innes
authors.affiliation: Mecru Clinical Research Unit, Sefako Makgatho Health Sciences University, Pretoria, South Africa.
authors.forename: Matsontso
authors.initials: M
authors.lastname: Mathebula
authors.affiliation: Vaccine Research Program, Division of AIDS, NIAID, NIH, Rockville, United States of America.
authors.forename: Mary
authors.initials: M
authors.lastname: Allen
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Carter
authors.initials: C
authors.lastname: Bentley
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Gilbert
authors.affiliation: Merck Research Laboratories, West Point, Pennsylvania, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Robertson
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Kublin
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.affiliation: Perinatal HIV Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa; South African Medical Research Council, Cape Town, South Africa.
authors.forename: Glenda E
authors.initials: GE
authors.lastname: Gray
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000453:epidemiology* / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D012307:Risk Factors; D013019:South Africa; D016896:Treatment Outcome
chemical_list: D016915:AIDS Vaccines