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PLoS One. 2015 Sep 14;10(9):e0137666. doi: 10.1371/journal.pone.0137666. eCollection 2015.

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

Author information

1
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
2
Desmond Tutu HIV Foundation, University of Cape Town, Cape Town, South Africa.
3
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.
4
Mecru Clinical Research Unit, Sefako Makgatho Health Sciences University, Pretoria, South Africa.
5
School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal and National Health Laboratory Service, Durban, South Africa.
6
Perinatal HIV Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
7
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.
8
Aurum Institute Clinical Research Site, Klerksdorp, South Africa.
9
Vaccine Research Program, Division of AIDS, NIAID, NIH, Rockville, United States of America.
10
Merck Research Laboratories, West Point, Pennsylvania, United States of America.
11
Perinatal HIV Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa; South African Medical Research Council, Cape Town, South Africa.

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).

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.

TRIAL REGISTRATION:

clinicaltrials.gov NCT00413725 SA National Health Research Database DOH-27-0207-1539.

PMID:
26368824
PMCID:
PMC4569275
DOI:
10.1371/journal.pone.0137666
[Indexed for MEDLINE]
Free PMC Article

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