PMID- 25090110 OWN - NLM STAT- MEDLINE DCOM- 20150414 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 8 DP - 2014 TI - Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine induced immune responses. PG - e103446 LID - 10.1371/journal.pone.0103446 [doi] LID - e103446 AB - BACKGROUND: Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, conducted in South Africa, suspended enrollment and vaccination when companion study, Step, was found non-efficacious. Although the vaccine did not prevent HIV-1 infection or lower viral-load setpoint, immune responses recognized clades B and C HIV-1 subtypes. We investigated predictors of the vaccine-induced antigen-specific immune responses. METHODS: Vaccine-induced immunogenicity was ascertained by interferon-gamma ELISpot assays on the first 186 enrolled participants receiving two vaccinations. Analyses, stratified by study arm/sex, were performed on baseline demographics [sex, age, Body Mass Index (BMI), site, Adenovirus Type-5 (Ad5) titer, Herpes Simplex Virus Type-2 (HSV2) status, heavy drinking]. Multivariate logistic regression determined predictors. RESULTS: Of the 186 participants, 53.7% (n = 100) were female, median BMI was 22.5 [IQR: 20.4-27.0], 85.5% (n = 159) were Ad5 seropositive, and 18.8% (n = 35) drank heavily. All vaccine recipients responded to both clade B (n = 87; 47%) and/or C (n = 74; 40%), p = 0.17. In multivariate analysis, female sex [Adjusted Odds Ratio (AOR): 6.478; p = 0.0159], overweight/obese BMI (AOR: 0.186; p = 0.0452), and heavy drinking (AOR: 0.270; p = 0.048) significantly predicted immune response to clade C for any antigens. A marginally significant predictor of clade C-pol antigen was female sex (AOR: 3.182; p = 0.0500). CONCLUSIONS: Sex, BMI, and heavy drinking affected vaccine-induced HIV-1 specific immune responses to clade C antigens. The role of female sex and overweight/obese BMI boosting and suppressing vaccine-induced HIV-1 specific immune responses, respectively, requires elucidation, including any effect on HIV vaccine efficacy, especially in the era of colliding epidemics (HIV and obesity). FAU - Hopkins, Kathryn L AU - Hopkins KL AD - Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. FAU - Laher, Fatima AU - Laher F AD - Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. FAU - Otwombe, Kennedy AU - Otwombe K AD - Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. FAU - Churchyard, Gavin AU - Churchyard G AD - Aurum Institute for Health Research, Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa. FAU - Bekker, Linda-Gail AU - Bekker LG AD - Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa. FAU - DeRosa, Stephen AU - DeRosa S AD - HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. FAU - Nchabeleng, Maphoshane AU - Nchabeleng M AD - Medunsa HIV Clinical Research Unit, University of Limpopo, Pretoria, South Africa. FAU - Mlisana, Koleka AU - Mlisana K AD - Centre for AIDS Programme for Research in South Africa & Department of Medical Microbiology, University of KwaZulu-Natal, Durban, South Africa. FAU - Kublin, James AU - Kublin J AD - HIV Vaccine Trials Network, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. FAU - Gray, Glenda AU - Gray G AD - Perinatal HIV Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. LA - eng GR - UM1 AI069519/AI/NIAID NIH HHS/United States GR - 5U01 AI068614/AI/NIAID NIH HHS/United States GR - U01 AI069453/AI/NIAID NIH HHS/United States GR - 5U01 AI069469/AI/NIAID NIH HHS/United States GR - UM1 AI068614/AI/NIAID NIH HHS/United States GR - 5U01 AI068618/AI/NIAID NIH HHS/United States GR - UM1 AI069453/AI/NIAID NIH HHS/United States GR - 5U01 AI069519/AI/NIAID NIH HHS/United States GR - 5U01 AI069453/AI/NIAID NIH HHS/United States GR - U01 AI069519/AI/NIAID NIH HHS/United States GR - 5U01 AI068635/AI/NIAID NIH HHS/United States GR - U01 AI068614/AI/NIAID NIH HHS/United States GR - U01 AI069469/AI/NIAID NIH HHS/United States GR - U01 AI068635/AI/NIAID NIH HHS/United States GR - U01 AI068618/AI/NIAID NIH HHS/United States GR - TW007373/0/TW/FIC NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural DEP - 20140804 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (AIDS Vaccines) RN - 0 (HIV Antigens) RN - 0 (gag Gene Products, Human Immunodeficiency Virus) RN - 0 (nef Gene Products, Human Immunodeficiency Virus) RN - 0 (pol Gene Products, Human Immunodeficiency Virus) SB - IM MH - AIDS Vaccines/*immunology MH - Adenoviridae MH - Demography MH - Enzyme-Linked Immunospot Assay MH - Female MH - HIV Antigens/immunology MH - HIV Infections/*immunology/*prevention & control MH - Humans MH - Male MH - Multivariate Analysis MH - Young Adult MH - gag Gene Products, Human Immunodeficiency Virus/*immunology MH - nef Gene Products, Human Immunodeficiency Virus/*immunology MH - pol Gene Products, Human Immunodeficiency Virus/*immunology PMC - PMC4121165 COIS- Competing Interests: The pharmaceutical company, Merck and Co Inc., sponsored the study products for the HVTN 503/Phambili clinical trial. There are no competing interests to declare, and these study products have not been marketed. This does not alter the authors' adherence to PLoS ONE policies on sharing data and materials. EDAT- 2014/08/05 06:00 MHDA- 2015/04/15 06:00 PMCR- 2014/08/04 CRDT- 2014/08/05 06:00 PHST- 2014/03/31 00:00 [received] PHST- 2014/06/30 00:00 [accepted] PHST- 2014/08/05 06:00 [entrez] PHST- 2014/08/05 06:00 [pubmed] PHST- 2015/04/15 06:00 [medline] PHST- 2014/08/04 00:00 [pmc-release] AID - PONE-D-14-13942 [pii] AID - 10.1371/journal.pone.0103446 [doi] PST - epublish SO - PLoS One. 2014 Aug 4;9(8):e103446. doi: 10.1371/journal.pone.0103446. eCollection 2014.