Disparate associations of HLA class I markers with HIV-1 acquisition and control of viremia in an African population

PLoS One. 2011;6(8):e23469. doi: 10.1371/journal.pone.0023469. Epub 2011 Aug 17.

Abstract

Background: Acquisition of human immunodeficiency virus type 1 (HIV-1) infection is mediated by a combination of characteristics of the infectious and the susceptible member of a transmission pair, including human behavioral and genetic factors, as well as viral fitness and tropism. Here we report on the impact of established and potential new HLA class I determinants of heterosexual HIV-1 acquisition in the HIV-1-exposed seronegative (HESN) partners of serodiscordant Zambian couples.

Methodology/principal findings: We assessed the relationships of behavioral and clinically documented risk factors, index partner viral load, and host genetic markers to HIV-1 transmission among 568 cohabiting couples followed for at least nine months. We genotyped subjects for three classical HLA class I genes known to influence immune control of HIV-1 infection. From 1995 to December 2006, 240 HESNs seroconverted and 328 remained seronegative. In Cox proportional hazards models, HLA-A*68:02 and the B*42-C*17 haplotype in HESN partners were significantly and independently associated with faster HIV-1 acquisition (relative hazards = 1.57 and 1.55; p = 0.007 and 0.013, respectively) after controlling for other previously established contributing factors in the index partner (viral load and specific class I alleles), in the HESN partner (age, gender), or in the couple (behavioral and clinical risk score). Few if any previously implicated class I markers were associated here with the rate of acquiring infection.

Conclusions/significance: A few HLA class I markers showed modest effects on acquisition of HIV-1 subtype C infection in HESN partners of discordant Zambian couples. However, the striking disparity between those few markers and the more numerous, different markers found to determine HIV-1 disease course makes it highly unlikely that, whatever the influence of class I variation on the rate of infection, the mechanism mediating that phenomenon is identical to that involved in disease control.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Black People / genetics
  • Female
  • Gene Frequency
  • Genotype
  • HIV Infections / epidemiology
  • HIV Infections / genetics
  • HIV Infections / transmission*
  • HIV Seronegativity
  • HIV-1 / isolation & purification*
  • HLA Antigens / genetics*
  • HLA-A Antigens / genetics
  • HLA-B Antigens / genetics
  • Haplotypes / genetics
  • Health Surveys
  • Heterosexuality / ethnology
  • Heterosexuality / statistics & numerical data
  • Humans
  • Male
  • Prevalence
  • Proportional Hazards Models
  • Risk Factors
  • Sexual Partners
  • Viremia / virology*
  • Young Adult
  • Zambia / epidemiology

Substances

  • HLA Antigens
  • HLA-A Antigens
  • HLA-A*68 antigen
  • HLA-B Antigens