title: HLA alleles association with changes in bone mineral density in HIV-1-infected adults changing treatment to tenofovir-emtricitabine or abacavir-lamivudine.
abstract: BACKGROUND
  There are limited data regarding the influence of human leukocyte antigen (HLA) polymorphisms on reduced bone mineral density (BMD). We investigated the relationship between HLA supertypes and BMD in HIV-infected adults changing their existing treatment to tenofovir-emtricitabine (TDF-FTC) or abacavir-lamivudine (ABC-3TC) in the STEAL study.
  
  
  METHODS
  Lumbar spine and right hip BMD were measured by Dual-energy X-ray absorptiometry (DXA). HLA genotypes at the 2-digit level were classified into class I and II supertypes. Student's t-tests were used to test the association between HLA supertypes and changes in hip and spine BMD over 96 weeks for the whole cohort and stratified by randomised groups. The relationship between HLA supertypes and BMD was also assessed in the subgroup of participants that were naïve to both ABC and TDF at study entry.
  
  
  RESULTS
  Class II supertypes were mainly associated with hip BMD change. Overall, compared to participants not carrying HLA-DQ3, participants expressing DQ3 had less bone loss over 96 weeks at both the hip and spine (hip: 0.003 vs. -0.006 g/cm2, 95%CI 0.002 to 0.017, p = 0.016; spine: 0.006 vs. -0.006 g/cm2, 95%CI 0.001 to 0.023, p = 0.041). In participants that were naïve to both ABC and TDF at baseline and randomised to TDF-FTC, DQ3 was significantly associated with less bone loss compared with those not carrying DQ3 (hip: 0.001 vs. -0.032 g/cm2; diff 0.033; 95%CI 0.017 to 0.049; p<0.001; spine: 0.007 vs. -0.023 g/cm2; diff 0.035; 95%CI 0.014 to 0.056; p = 0.001).
  
  
  CONCLUSIONS
  In this cohort of HIV-infected adults, there was an association between bone status and HLA supertypes, particularly HLA-DQ3.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00192634.
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia.
authors.forename: Hila
authors.initials: H
authors.lastname: Haskelberg
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia.
authors.forename: Damien V
authors.initials: DV
authors.lastname: Cordery
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia.
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia; St Vincent's Centre for Applied Medical Research, Darlinghurst, New South Wales, Australia.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Kelleher
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia; St Vincent's Centre for Applied Medical Research, Darlinghurst, New South Wales, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia.
authors.forename: Sean
authors.initials: S
authors.lastname: Emery
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000483:Alleles; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015519:Bone Density / Q000187:drug effects / Q000235:genetics*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D004338:Drug Combinations; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D000068698:Tenofovir; D000099227:Abacavir
chemical_list: D000225:Adenine; D019380:Anti-HIV Agents; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D004338:Drug Combinations; D000068679:Emtricitabine; D006683:HLA-DQ Antigens; D019259:Lamivudine; D063065:Organophosphonates; D000068698:Tenofovir; C051569:HLA-DQ3 antigen; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir