Background: We studied the association of obesity-related single-nucleotide polymorphisms (OR-SNPs) with weight gain after antiretroviral therapy (ART) in people with human immunodeficiency virus (HIV; PWH)., Methods: Participants were ART-naive PWH from the Spanish HIV Research Cohort who started ART from 2014 onward and had blood/DNA deposited in the cohort Biobank. The primary outcome was change in weight at 96 weeks after starting ART. We genotyped 14 OR-SNPs from a meta-analysis of genome-wide association studies of body mass index (BMI) loci. Changes over time in weight and BMI were studied using adjusted linear mixed models., Results: A total of 1021 PWH were included. The mean weight gain over 96 weeks was 2.90 (95% confidence interval, 2.54-3.26) kg. Factors associated with higher weight gain were female sex, birth in sub-Saharan Africa, prior AIDS, CD4+ <200 cells/µL, HIV-RNA >100 000 copies/mL, negative hepatitis C virus serology, and use of tenofovir alafenamide. A significant association was found between ZC3H4 rs3810291 GG genotype and BCDIN3D/FAIM2 rs7138803 GG genotype polymorphisms and weight and BMI increase. The estimated adjusted mean (standard error [SE]) of weight gain was 4.26 (0.56) kg in ZC3H4 rs3810291 GG carriers and 2.66 (0.19) kg in AA/AG carriers (P = .007). Likewise the estimated weight gain at 96 weeks was 3.35 (0.29) kg in BCDIN3D/FAIM2 rs7138803 GG carriers and 2.51 (0.24) kg in AG/AA carriers (P = .020)., Conclusions: Genetic factors may play a role in weight gain after ART initiation. Further work is needed to replicate our findings and understand how the identified SNPs lead to higher weight gain in this context., Competing Interests: Potential conflicts of interest. J. B. reports honoraria for advice or public speaking from Gilead Sciences, Inc, GSK, Janssen Pharmaceuticals, MSD, and ViiV Healthcare; grants from Gilead Sciences, Inc, MSD, and ViiV Healthcare; and support for attending meetings and/or travel from MSD, ViiV Healthcare, and Janssen Pharmaceuticals. I. J. reports honoraria for advice or public speaking from GILEAD, and ViiV Healthcare; honoraria for performing statistical analyses from Fundación Investigación Biomédica Hospital Gregorio Marañón and grants from MSD. J. G.-G. reports honoraria for advice or public speaking from Gilead Sciences, Inc, Janssen Pharmaceuticals, MSD, and ViiV Healthcare; grants or contracts from MSD, ViiV Healthcare, and Gilead Sciences, Inc; support for attending meetings and/or travel from Gilead Sciences, Inc (paid to author); and participation on a DSMB or advisory board for ViiV Healthcare and Janssen-Cilag, S.A. D. D. reports honoraria for public speaking from Gilead Sciences, Inc, Janssen Pharmaceuticals, and ViiV Healthcare (some of this payment was made to author's institution); support for attending meetings and/or travel from Gilead Sciences, Inc; and plays a role in the Spanish AIDS Society and Spanish HIV/AIDS Research Network of Excellence. J. O. reports honoraria for advice or public speaking from Gilead Sciences, Inc, Janssen Pharmaceuticals, MSD, ViiV Healthcare, Pfizer, and GSK; grants from Gilead Sciences, Inc, MSD, and ViiV Healthcare, including consulting fees from Janssen, ViiV, MSD, Gilead Sciences, Inc, and Pfizer; and support for attending meetings and/or travel from Gilead Sciences, Inc, and ViiV. P. D. reports honoraria for advice or public speaking or grants and participation on a DSMB or advisory board from AbbVie, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Inc, GSK, MSD, Janssen Pharmaceuticals, Pfizer, Theratechnologies, and ViiV Healthcare. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.) more...