title: Changes in Bone Mineral Density After Initiation of Antiretroviral Treatment With Tenofovir Disoproxil Fumarate/Emtricitabine Plus Atazanavir/Ritonavir, Darunavir/Ritonavir, or Raltegravir.
abstract: BACKGROUND
  Specific antiretroviral therapy (ART) medications and the severity of human immunodeficiency virus (HIV) disease before treatment contribute to bone mineral density (BMD) loss after ART initiation.
  
  
  METHODS
  We compared the percentage change in BMD over 96 weeks in 328 HIV-infected, treatment-naive individuals randomized equally to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). We also determined whether baseline levels of inflammation markers and immune activation were independently associated with BMD loss.
  
  
  RESULTS
  At week 96, the mean percentage changes from baseline in spine and hip BMDs were similar in the protease inhibitor (PI) arms (spine: -4.0% in the ATV/r group vs -3.6% in the DRV/r [P = .42]; hip: -3.9% in the ATV/r group vs -3.4% in the DRV/r group [P = .36]) but were greater in the combined PI arms than in the RAL arm (spine: -3.8% vs -1.8% [P < .001]; hip: -3.7% vs -2.4% [P = .005]). In multivariable analyses, higher baseline concentrations of high-sensitivity C-reactive protein, interleukin 6, and soluble CD14 were associated with greater total hip BMD loss, whereas markers of CD4(+) T-cell senescence and exhaustion (CD4(+)CD28(-)CD57(+)PD1(+)) and CD4(+) T-cell activation (CD4(+)CD38(+)HLA-DR(+)) were associated with lumbar spine BMD loss.
  
  
  CONCLUSIONS
  BMD losses 96 weeks after ART initiation were similar in magnitude among patients receiving PIs, ATV/r, or DRV/r but lowest among those receiving RAL. Inflammation and immune activation/senescence before ART initiation independently predicted subsequent BMD loss.
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Todd T
authors.initials: TT
authors.lastname: Brown
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Carlee
authors.initials: C
authors.lastname: Moser
authors.affiliation: David Geffen School of Medicine, University of California-Los Angeles.
authors.forename: Judith S
authors.initials: JS
authors.lastname: Currier
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
authors.affiliation: Social and Scientific Systems, Washington D.C.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rothenberg
authors.affiliation: David Geffen School of Medicine, University of California-Los Angeles.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kelesidis
authors.affiliation: David Geffen School of Medicine, University of California-Los Angeles.
authors.forename: Otto
authors.initials: O
authors.lastname: Yang
authors.affiliation: Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dubé
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Murphy
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: James H
authors.initials: JH
authors.lastname: Stein
authors.affiliation: Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Grace A
authors.initials: GA
authors.lastname: McComsey
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000069446:Atazanavir Sulfate / Q000009:adverse effects / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D000069454:Darunavir / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000068679:Emtricitabine / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006678:HIV / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy* / Q000503:physiopathology; D019428:HIV Integrase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068898:Raltegravir Potassium / Q000009:adverse effects / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use; D000068698:Tenofovir / Q000009:adverse effects / Q000627:therapeutic use; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D000068898:Raltegravir Potassium; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000068679:Emtricitabine; D019438:Ritonavir; D000069454:Darunavir
keywords: bone mineral density; human immunodeficiency virus; inflammation; integrase inhibitor; protease inhibitor