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

J Infect Dis. 2019 Sep 13;220(8):1325-1334. 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.

Keywords: GWAS; HIV-1; HLA; genome-wide association study; host genetics; viral load.

Publication types

  • Clinical Trial, Phase IV
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Anti-Retroviral Agents / pharmacology*
  • Anti-Retroviral Agents / therapeutic use
  • Female
  • Genome-Wide Association Study
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / immunology*
  • HIV-1 / isolation & purification
  • Histocompatibility Antigens Class I / genetics*
  • 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 / genetics*
  • Viral Load / immunology


  • Anti-Retroviral Agents
  • Histocompatibility Antigens Class I