title: HLA-B alleles associate consistently with HIV heterosexual transmission, viral load, and progression to AIDS, but not susceptibility to infection.
abstract: OBJECTIVE
  HLA class I polymorphism is known to affect the rate of progression to AIDS after infection with HIV-1. Here we test the consistency of HLA-B allelic effects on progression to AIDS, heterosexual HIV transmission, and 'set point' viral levels.
  
  
  METHODS
  We used adjusted Cox proportional hazard models in previously published relative hazard values for the effect of HLA-B alleles on progression to AIDS (n = 1089). The transmission study included 303 HIV-1-infected men with hemophilia and their 323 female sex partners (Multicenter Hemophilia Cohort Study cohort). Among 259 HIV-1 seroconverters (Multicenter AIDS Cohort Study cohort), HIV RNA levels at 'set point' were determined in stored plasma samples by a reverse-transcription polymerase chain reaction assay. HLA-B genotyping was performed by sequence-specific oligonucleotide hybridization and DNA sequencing.
  
  
  RESULTS
  Several HLA-B alleles showed consistent associations for AIDS risk, infectivity, and 'set point' HIV RNA. HLA-B*35 was associated with more rapid progression to AIDS (relative hazard 1.39; P = 0.008), greater infectivity (odds ratio 3.14; P = 0.002), and higher HIV RNA (P = 0.01), whereas the presence of either B*27 or B*57 associated with slower progression to AIDS (B*27: relative hazard 0.49, P < 0.001; B*57: relative hazard 0.40, P < 0.0001), less infectivity (odds ratio 0.22 and 0.31, respectively, though not significant), and lower viral levels (P < 0.0001). Importantly, HLA-B polymorphism in female partners was not associated with susceptibility to HIV-1 infection.
  
  
  CONCLUSIONS
  HLA-B polymorphisms that affect the risk of AIDS may also alter HIV-1 infectivity, probably through the common mechanism of viral control, but they do not appear to protect against infection in our cohort.
authors.affiliation: Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC Frederick Inc., NCI-Frederick, Frederick, Maryland 21702, USA.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Gao
authors.forename: Thomas R
authors.initials: TR
authors.lastname: O'Brien
authors.forename: Tania M
authors.initials: TM
authors.lastname: Welzel
authors.forename: Darlene
authors.initials: D
authors.lastname: Marti
authors.forename: Ying
authors.initials: Y
authors.lastname: Qi
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: John
authors.initials: J
authors.lastname: Phair
authors.forename: Ruth
authors.initials: R
authors.lastname: Pfeiffer
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D005060:Europe; D005260:Female; D005838:Genotype; D006679:HIV Seropositivity / Q000235:genetics / Q000276:immunology* / Q000635:transmission; D015497:HIV-1 / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology*; D006467:Hemophilia A / Q000235:genetics / Q000276:immunology* / Q000821:virology; D020010:Heterosexuality; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012747:Sexual Partners; D014481:United States; D019562:Viral Load; D055815:Young Adult
chemical_list: D015235:HLA-B Antigens