HLA alleles association with changes in bone mineral density in HIV-1-infected adults changing treatment to tenofovir-emtricitabine or abacavir-lamivudine

• Published in: PloS one 2014-03, Vol.9 (3), p.e93333
• Main Authors: Haskelberg, Hila, Cordery, Damien V, Amin, Janaki, Kelleher, Anthony D, Cooper, David A, Emery, Sean
• Format: Article
• Language: English
• Subjects: Abacavir; Acquired immune deficiency syndrome; Adenine - analogs & derivatives; Adenine - therapeutic use; Adult; Adults; AIDS; Alleles; Anti-HIV Agents - therapeutic use; Antigens; Antiretroviral agents; Antiretroviral drugs; Antiretroviral Therapy, Highly Active - methods; Bone density; Bone Density - drug effects; Bone Density - genetics; Bone loss; Bone mineral density; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Dideoxynucleosides - therapeutic use; Drug Combinations; Dual energy X-ray absorptiometry; Emtricitabine; Energy measurement; Ethics; Female; Gene loci; Genomics; Genotypes; Health risk assessment; Health services; Hip; Histocompatibility antigen HLA; HIV; HIV Infections - drug therapy; HIV Infections - genetics; HIV-1 - drug effects; HLA antigens; HLA-DQ Antigens - genetics; Hospitals; Human immunodeficiency virus; Humans; Immunology; Infectious diseases; Lamivudine; Lamivudine - therapeutic use; Leukocytes; Male; Medical research; Middle Aged; Organophosphonates - therapeutic use; Osteoporosis; Randomization; Reverse transcriptase inhibitors; Spine; Spine (lumbar); Tenofovir; Womens health
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0093333

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. 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. 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