PMID- 24681993 OWN - NLM STAT- MEDLINE DCOM- 20150601 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 3 DP - 2014 TI - HLA alleles association with changes in bone mineral density in HIV-1-infected adults changing treatment to tenofovir-emtricitabine or abacavir-lamivudine. PG - e93333 LID - 10.1371/journal.pone.0093333 [doi] LID - e93333 AB - 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 naive 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 naive 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. TRIAL REGISTRATION: Clinicaltrials.gov NCT00192634. FAU - Haskelberg, Hila AU - Haskelberg H AD - The Kirby Institute, University of New South Wales, Sydney, Australia. FAU - Cordery, Damien V AU - Cordery DV AD - The Kirby Institute, University of New South Wales, Sydney, Australia. FAU - Amin, Janaki AU - Amin J AD - The Kirby Institute, University of New South Wales, Sydney, Australia. FAU - Kelleher, Anthony D AU - Kelleher AD AD - The Kirby Institute, University of New South Wales, Sydney, Australia; St Vincent's Centre for Applied Medical Research, Darlinghurst, New South Wales, Australia. FAU - Cooper, David A AU - Cooper DA AD - The Kirby Institute, University of New South Wales, Sydney, Australia; St Vincent's Centre for Applied Medical Research, Darlinghurst, New South Wales, Australia. FAU - Emery, Sean AU - Emery S AD - The Kirby Institute, University of New South Wales, Sydney, Australia. CN - STEAL Study Group LA - eng SI - ClinicalTrials.gov/NCT00192634 PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140328 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Anti-HIV Agents) RN - 0 (Dideoxynucleosides) RN - 0 (Drug Combinations) RN - 0 (HLA-DQ Antigens) RN - 0 (HLA-DQ3 antigen) RN - 0 (Organophosphonates) RN - 0 (abacavir, lamivudine drug combination) RN - 0W860991D6 (Deoxycytidine) RN - 2T8Q726O95 (Lamivudine) RN - 99YXE507IL (Tenofovir) RN - G70B4ETF4S (Emtricitabine) RN - JAC85A2161 (Adenine) SB - IM MH - Adenine/*analogs & derivatives/therapeutic use MH - Adult MH - Alleles MH - Anti-HIV Agents/therapeutic use MH - Antiretroviral Therapy, Highly Active/methods MH - Bone Density/drug effects/*genetics MH - Deoxycytidine/*analogs & derivatives/therapeutic use MH - Dideoxynucleosides/*therapeutic use MH - Drug Combinations MH - Emtricitabine MH - Female MH - HIV Infections/*drug therapy/*genetics MH - HIV-1/drug effects MH - HLA-DQ Antigens/*genetics MH - Humans MH - Lamivudine/*therapeutic use MH - Male MH - Middle Aged MH - Organophosphonates/*therapeutic use MH - Tenofovir PMC - PMC3969319 COIS- Competing Interests: Sean Emery is a PLOS ONE Editorial Board member. This does not alter adherence to PLOS ONE Editorial policies and criteria. Hila Haskelberg, Damien Cordery and Janaki Amin declare no conflict of interest. Anthony Kelleher has received travel grant support from Merck Research Laboratories on two occasions since 2010 and from ViiV for consultancy work. David Cooper has received grants and consultancies and Honoraria from Gilead and ViiV. Sean Emery has received research grant support from Abbvie, Gilead Sciences, Merck Research Laboratories, Pfizer, and ViiV Healthcare. This does not alter adherence to PLOS ONE policies on sharing data and materials. FIR - Allworth, Anthony IR - Allworth A FIR - Anderson, Jonathan IR - Anderson J FIR - Baker, David IR - Baker D FIR - Bloch, Mark IR - Bloch M FIR - Boyd, Mark IR - Boyd M FIR - Chuah, John IR - Chuah J FIR - Cooper, David IR - Cooper D FIR - Davies, Stephen IR - Davies S FIR - Dayan, Linda IR - Dayan L FIR - Donohue, William IR - Donohue W FIR - Doong, Nicholas IR - Doong N FIR - Dwyer, Dominic IR - Dwyer D FIR - Dyer, John IR - Dyer J FIR - Finlayson, Robert IR - Finlayson R FIR - Giles, Michelle IR - Giles M FIR - Gordon, David IR - Gordon D FIR - Kelly, Mark IR - Kelly M FIR - Medland, Nicholas IR - Medland N FIR - Moore, Richard IR - Moore R FIR - Nolan, David IR - Nolan D FIR - Orth, David IR - Orth D FIR - Post, Jeffrey IR - Post J FIR - Quin, John IR - Quin J FIR - Read, Tim IR - Read T FIR - Roth, Norman IR - Roth N FIR - Russell, Darren IR - Russell D FIR - Shaw, David IR - Shaw D FIR - Smith, David IR - Smith D FIR - Smith, Don IR - Smith D FIR - Street, Alan IR - Street A FIR - Tee, Ban Kiem IR - Tee BK FIR - Woolley, Ian IR - Woolley I EDAT- 2014/04/01 06:00 MHDA- 2015/06/02 06:00 PMCR- 2014/03/28 CRDT- 2014/04/01 06:00 PHST- 2013/12/04 00:00 [received] PHST- 2014/03/03 00:00 [accepted] PHST- 2014/04/01 06:00 [entrez] PHST- 2014/04/01 06:00 [pubmed] PHST- 2015/06/02 06:00 [medline] PHST- 2014/03/28 00:00 [pmc-release] AID - PONE-D-13-50648 [pii] AID - 10.1371/journal.pone.0093333 [doi] PST - epublish SO - PLoS One. 2014 Mar 28;9(3):e93333. doi: 10.1371/journal.pone.0093333. eCollection 2014.