title: Disparate associations of HLA class I markers with HIV-1 acquisition and control of viremia in an African population.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Dongning
authors.initials: D
authors.lastname: He
authors.forename: Ilene
authors.initials: I
authors.lastname: Brill
authors.forename: Rakhi
authors.initials: R
authors.lastname: Malhotra
authors.forename: Joseph
authors.initials: J
authors.lastname: Mulenga
authors.forename: Susan
authors.initials: S
authors.lastname: Allen
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
mesh_terms: D000328:Adult; D044383:Black People / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics / Q000635:transmission*; D018023:HIV Seronegativity; D015497:HIV-1 / Q000302:isolation & purification*; D006680:HLA Antigens / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006306:Health Surveys; D020010:Heterosexuality / Q000208:ethnology / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D015995:Prevalence; D016016:Proportional Hazards Models; D012307:Risk Factors; D012747:Sexual Partners; D014766:Viremia / Q000821:virology*; D055815:Young Adult; D015024:Zambia / Q000453:epidemiology
chemical_list: D006680:HLA Antigens; D015234:HLA-A Antigens; C053029:HLA-A*68 antigen; D015235:HLA-B Antigens