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

• Published in: The Journal of infectious diseases 2019-09, Vol.220 (8), p.1325-1334
• Main Authors: Ekenberg, Christina, Tang, Man-Hung, Zucco, Adrian G., Murray, Daniel D., MacPherson, Cameron Ross, Hu, Xiaojun, Sherman, Brad T., Losso, Marcelo H., Wood, Robin, Paredes, Roger, Molina, Jean-Michel, Helleberg, Marie, Jina, Nureen, Kityo, Cissy M., Florence, Eric, Polizzotto, Mark N., Neaton, James D., Lane, H. Clifford, Lundgren, Jens D.
• Format: Article
• Language: English
• Subjects: Adult; Alleles; Anti-Retroviral Agents - pharmacology; Anti-Retroviral Agents - therapeutic use; Antiretroviral drugs; Antiretroviral therapy; Demography; Drug therapy; Female; Genetic diversity; Genome-wide association studies; Genome-Wide Association Study; Genomes; Histocompatibility antigen HLA; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; HIV; HIV Infections - drug therapy; HIV Infections - genetics; HIV Infections - immunology; HIV Infections - virology; HIV-1 - immunology; HIV-1 - isolation & purification; HIV/AIDS; Host-Pathogen Interactions - genetics; Host-Pathogen Interactions - immunology; Human immunodeficiency virus; Humans; Major and Brief Reports; Major histocompatibility complex; Male; Middle Aged; Polymorphism, Single Nucleotide; Population genetics; Single-nucleotide polymorphism; Time Factors; Viral Load - drug effects; Viral Load - genetics; Viral Load - immunology
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiz294

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.