TY - JOUR
T1 - Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa
T2 - Unblinded, long-term follow-up of the phase 2b HVTN 503/Phambili study
AU - Gray, Glenda E.
AU - Moodie, Zoe
AU - Metch, Barbara
AU - Gilbert, Peter B.
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 - McElrath, M. Julie
AU - Robertson, Michael
AU - Kublin, James
AU - Corey, Lawrence
N1 - Funding Information:
Our study was funded by grants from the National Institute of Allergy and Infectious Diseases to the HIV Vaccine Trials Network (HVTN; 5U01 AI068614, 5U01 AI068618, 5U01 AI068635, 5U01 AI069453, 5U01 AI069519, 5U01 AI069469 ), and by Merck and Company. The South African AIDS Vaccine Initiative of the Medical Research Council provided support to the clinical trial sites. We thank the Phambili study volunteers and the staff and community members at each of the Phambili study sites; the staff at the HVTN administrative core, Statistical Center for HIV/AIDS Research and Prevention, and central laboratory; the staff at Merck; and Elizabeth Adams at the Division of AIDS in the National Institute of Allergy and Infectious Diseases for their facilitation of the study design and conduct. The opinions expressed in this Article are those of the authors and do not represent the official views of the US National Institute of Allergy and Infectious Diseases.
Funding Information:
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. MR is employee of and owns stock in Merck. All other authors declare that they have no competing interests.
PY - 2014/5
Y1 - 2014/5
N2 - 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. 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. 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. 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. Funding: National Institute of Allergy and Infectious Diseases, Merck, and South African Medical Research Council.
AB - 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. 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. 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. 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. Funding: National Institute of Allergy and Infectious Diseases, Merck, and South African Medical Research Council.
UR - http://www.scopus.com/inward/record.url?scp=84899445004&partnerID=8YFLogxK
U2 - 10.1016/S1473-3099(14)70020-9
DO - 10.1016/S1473-3099(14)70020-9
M3 - Article
C2 - 24560541
AN - SCOPUS:84899445004
SN - 1473-3099
VL - 14
SP - 388
EP - 396
JO - The Lancet Infectious Diseases
JF - The Lancet Infectious Diseases
IS - 5
ER -