1. Association Between Single-Nucleotide Polymorphisms in HLA Alleles and Human Immunodeficiency Virus Type 1 Viral Load in Demographically Diverse, Antiretroviral Therapy-Naive Participants From the Strategic Timing of AntiRetroviral Treatment Trial.
- Author
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Ekenberg C, Tang MH, Zucco AG, Murray DD, MacPherson CR, Hu X, Sherman BT, Losso MH, Wood R, Paredes R, Molina JM, Helleberg M, Jina N, Kityo CM, Florence E, Polizzotto MN, Neaton JD, Lane HC, and Lundgren JD
- Subjects
- Adult, Alleles, Anti-Retroviral Agents therapeutic use, Female, Genome-Wide Association Study, HIV Infections genetics, HIV Infections immunology, HIV Infections virology, HIV-1 isolation & purification, Histocompatibility Antigens Class I immunology, Host-Pathogen Interactions genetics, Host-Pathogen Interactions immunology, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Time Factors, Viral Load drug effects, Viral Load immunology, Anti-Retroviral Agents pharmacology, HIV Infections drug therapy, HIV-1 immunology, Histocompatibility Antigens Class I genetics, Viral Load genetics
- 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., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
- Published
- 2019
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