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Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa: unblinded, long-term follow-up of the phase 2b HVTN 503/Phambili study.
- Source :
-
The Lancet. Infectious diseases [Lancet Infect Dis] 2014 May; Vol. 14 (5), pp. 388-96. Date of Electronic Publication: 2014 Feb 20. - Publication Year :
- 2014
-
Abstract
- Background: The HVTN 503/Phambili study, which assessed the efficacy of the Merck Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine in South Africa, was stopped when futility criteria in the Step study (assessing the same vaccine in the Americas, Caribbean, and Australia) were met. Here we report long-term follow-up data.<br />Methods: HVTN 503/Phambili was a double-blind, placebo-controlled, randomised trial that recruited HIV-1 uninfected, sexually active adults aged 18-35 years from five sites in South Africa. Eligible participants were randomly assigned (1:1) by computer-generated random numbers to either vaccine or placebo, stratified by site and sex. Cox proportional hazards models were used to estimate HIV-1 infection in the modified intention-to-treat cohort, all of whom were unmasked early in follow-up. The trial is registered with ClinicalTrials.gov, number NCT00413725 and the South African National Health Research Database, number DOH-27-0207-1539.<br />Findings: Between Jan 24, 2007, and Sept 19, 2007, 801 participants (26·7%) of a planned 3000 were randomly assigned (400 to vaccine, 401 to placebo); 216 (27%) received only one injection, 529 (66%) received only two injections, and 56 (7%) received three injections. At a median follow-up of 42 months (IQR 31-42), 63 vaccine recipients (16%) had HIV-1 infection compared with 37 placebo recipients (9%; adjusted HR 1·70, 95% CI 1·13-2·55; p=0·01). Risk for HIV-1 infection did not differ according to the number of vaccinations received, sex, circumcision, or adenovirus type 5 (Ad5) serostatus. Differences in risk behaviour at baseline or during the study, or annualised dropout rate (7·7% [95% CI 6·2-9·5] for vaccine recipients vs 8·8% [7·1-10·7] for placebo recipients; p=0·40) are unlikely explanations for the increased rate of HIV-1 infections seen in vaccine recipients.<br />Interpretation: The increased risk of HIV-1 acquisition in vaccine recipients, irrespective of number of doses received, warrants further investigation to understand the biological mechanism. We caution against further use of the Ad5 vector for HIV vaccines.<br />Funding: National Institute of Allergy and Infectious Diseases, Merck, and South African Medical Research Council.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Subjects :
- Adolescent
Adult
Double-Blind Method
Female
Follow-Up Studies
HIV Infections epidemiology
Humans
Incidence
Male
Proportional Hazards Models
Risk Assessment
South Africa
Vaccines, Synthetic immunology
Young Adult
AIDS Vaccines administration & dosage
Adenoviridae genetics
Genetic Vectors
HIV Infections prevention & control
Protein Precursors immunology
gag Gene Products, Human Immunodeficiency Virus immunology
nef Gene Products, Human Immunodeficiency Virus immunology
pol Gene Products, Human Immunodeficiency Virus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1474-4457
- Volume :
- 14
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The Lancet. Infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 24560541
- Full Text :
- https://doi.org/10.1016/S1473-3099(14)70020-9