Abstract
The impact of variation in host genetics on replication of human immunodeficiency virus type 1 (HIV-1) in demographically diverse populations remains uncertain. In the current study, we performed a genome-wide screen for associations of single-nucleotide polymorphisms (SNPs) to viral load (VL) in antiretroviral therapy-naive participants (n = 2440) with varying demographics from the Strategic Timing of AntiRetroviral Treatment (START) trial. Associations were assessed using genotypic data generated by a customized SNP array, imputed HLA alleles, and multiple linear regression. Genome-wide significant associations between SNPs and VL were observed in the major histocompatibility complex class I region (MHC I), with effect sizes ranging between 0.14 and 0.39 log10 VL (copies/mL). Supporting the SNP findings, we identified several HLA alleles significantly associated with VL, extending prior observations that the (MHC I) is a major host determinant of HIV-1 control with shared genetic variants across diverse populations and underscoring the limitations of genome-wide association studies as being merely a screening tool.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1325-1334 |
| Number of pages | 10 |
| Journal | Journal of Infectious Diseases |
| Volume | 220 |
| Issue number | 8 |
| DOIs | |
| State | Published - Sep 13 2019 |
Bibliographical note
Funding Information:Potential conflicts of interest. M. H. L. has received research grants from the Ministry of Science and Technology and the Ministry of Health (both in Argentina), the University of New South Wales, Family Health International, Westat, and ViiV. R. P. has received research support from and has consulted for MSD, ViiV Healthcare, and Gilead Sciences; he is coinventor for a patent titled “Enhanced rapid immunogen selection method for HIV gp120 variants” (application/patent no. EP 12382328.8-1405). 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.
Funding Information:
This study was funded by the Danish National Research Foundation (grant DNRF126) and the National Institute of Allergy and Infectious Diseases, Division of Clinical Research and Division of AIDS (National Institutes of Health grants UM1-AI068641 and UM1-AI120197). The START trial was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health Clinical Center, National Cancer Institute, National Heart, Lung, and Blood Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Agence Nationale de Recherches sur le SIDA et les Hpatites Virales (France), National Health and Medical Research Council (Australia), National Research Foundation (Denmark), Bundes Ministerium fur Bildung und Forschung (Germany), European AIDS Treatment Network, Medical Research Council (United Kingdom), National Institute for Health Research, National Health Service (United Kingdom), and the University of Minnesota. Antiretroviral drugs were donated to the central drug repository by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, and Merck. We would like to thank all participants in the Strategic Timing of AntiRetroviral Treatment (START) trial and all trial investigators. (See Lundgren et al [21] for the complete list of START investigators.)
Funding Information:
Financial support. This study was funded by the Danish National Research Foundation (grant DNRF126) and the National Institute of Allergy and Infectious Diseases, Division of Clinical Research and Division of AIDS (National Institutes of Health grants UM1-AI068641 and UM1-AI120197). The START trial was supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health Clinical Center, National Cancer Institute, National Heart, Lung, and Blood Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France), National Health and Medical Research Council (Australia), National Research Foundation (Denmark), Bundes Ministerium für Bildung und Forschung (Germany), European AIDS Treatment Network, Medical Research Council (United Kingdom), National Institute for Health Research, National Health Service (United Kingdom), and the University of Minnesota. Antiretroviral drugs were donated to the central drug repository by AbbVie, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline/ViiV Healthcare, Janssen Scientific Affairs, and Merck.
Publisher Copyright:
© 2019 The Author(s).
Keywords
- GWAS
- HIV-1
- HLA
- genome-wide association study
- host genetics
- viral load
