title: Continuous antiretroviral therapy decreases bone mineral density.
abstract: OBJECTIVE
  To assess the effects of antiretroviral therapy (ART) on bone mineral density (BMD) DESIGN: Randomized comparison of continuous ART (viral suppression group; VS) with intermittent ART (drug conservation group; DC) SETTING: Outpatient clinics in the United States, Australia, and Spain.
  
  
  METHODS
  Participants in the Strategies for Management of Antiretroviral Therapy (SMART) Body Composition substudy.
  
  
  METHODS
  Annual hip and spine BMD by dual-energy radiographic absorptiometry (DXA) and spine BMD by quantitative computed tomography (qCT).
  
  
  METHODS
  Comparisons were by intention-to-treat analysis, using longitudinal models for change in BMD. Risk factors for BMD loss were evaluated.
  
  
  RESULTS
  The 214 participants (median 44 years, 19% female participants, 73% on ART; median T-scores -0.5 total hip, -0.7 spine DXA, -0.9 spine qCT; 98 randomized to VS and 116 to DC) were followed for a mean 2.4 years. With continuous ART, BMD declined per year by 0.8% (hip), 0.4% (spine DXA), and 2.4% (spine qCT). BMD declined significantly less with intermittent ART. Estimated DC minus VS group differences in mean BMD change through follow-up were 1.4% [hip; 95% confidence interval (CI) 0.6-2.3; P = 0.002], 1.3% (spine DXA; 95% CI 0.1-2.4, P = 0.03), and 3.0% (spine qCT; 95% CI 0.8-5.2, P = 0.007). No consistent drug-specific association with BMD decline was found. In the parent study, 10 of 2753 participants in the VS group and two of 2720 in the DC group reported serious fractures (hazard ratio 4.9; 95% CI 1.1-22.5; P = 0.04).
  
  
  CONCLUSIONS
  Continuous ART is associated with decline in BMD and possibly more fractures relative to intermittent, CD4 cell count-guided ART.
authors.affiliation: Coordinating Center for Biometric Research, University of Minnesota, Minneapolis, Minnesota 55414, USA. birgit@ccbr.umn.edu
authors.forename: Birgit
authors.initials: B
authors.lastname: Grund
authors.forename: Grace
authors.initials: G
authors.lastname: Peng
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Gibert
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Hoy
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Isaksson
authors.forename: Judith C
authors.initials: JC
authors.lastname: Shlay
authors.forename: Esteban
authors.initials: E
authors.lastname: Martinez
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Fehmida
authors.initials: F
authors.lastname: Visnegarwala
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Carr
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods; D015519:Bone Density / Q000187:drug effects*; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000209:etiology / Q000503:physiopathology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D015497:HIV-1; D006621:Hip Joint / Q000503:physiopathology; D006801:Humans; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000139:chemically induced* / Q000503:physiopathology; D012307:Risk Factors; D014057:Tomography, X-Ray Computed
chemical_list: D019380:Anti-HIV Agents