title: A Single-dose Zoledronic Acid Infusion Prevents Antiretroviral Therapy-induced Bone Loss in Treatment-naive HIV-infected Patients: A Phase IIb Trial.
abstract: BACKGROUND
  Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are associated with bone loss leading to increased fracture rate among HIV-infected individuals. ART-induced bone loss is most intense within the first 48 weeks of therapy, providing a window for prophylaxis with long-acting antiresorptives.
  
  
  METHODS
  In a phase 2, double-blind, placebo-controlled trial, we randomized 63 nonosteoporotic, ART-naive adults with HIV initiating ART with atazanavir/ritonavir + tenofovir/emtricitabine to a single zoledronic acid (ZOL) infusion (5 mg) vs placebo to determine the efficacy of ZOL in mitigating ART-induced bone loss. Plasma bone turnover markers and bone mineral density (BMD) were performed at weeks 0, 12, 24, and 48 weeks. Primary outcome was change in C-terminal telopeptide of collagen at 24 weeks. Repeated-measures analyses using mixed linear models were used to estimate and compare study endpoints.
  
  
  RESULTS
  The ZOL arm had a 65% reduction in bone resorption relative to the placebo arm at 24 weeks (0.117 ng/mL vs 0.338 ng/mL; P < .001). This effect of ZOL occurred as early as 12 weeks (73% reduction; P < .001) and persisted through week 48 (57% reduction; P < .001). The ZOL arm had an 8% higher lumbar spine BMD at 12 weeks relative to the placebo arm (P = .003), and remained 11% higher at 24 and 48 weeks. Similar trends were observed in the hip and femoral neck.
  
  
  CONCLUSIONS
  A single dose of ZOL administered at ART initiation prevented ART-induced bone loss through the first 48 weeks of ART, the period when ART-induced bone loss is most pronounced. Validation of these results in larger multicenter randomized clinical trials is warranted.
  
  
  BACKGROUND
  NCT01228318.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine.|Grady Healthcare System.
authors.forename: Ighovwerha
authors.initials: I
authors.lastname: Ofotokun
authors.affiliation: Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine.
authors.forename: Kehmia
authors.initials: K
authors.lastname: Titanji
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine.|Grady Healthcare System.
authors.forename: Cecile D
authors.initials: CD
authors.lastname: Lahiri
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine.
authors.forename: Aswani
authors.initials: A
authors.lastname: Vunnava
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine.
authors.forename: Antonina
authors.initials: A
authors.lastname: Foster
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Sanford
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine.|Grady Healthcare System.
authors.forename: Anandi N
authors.initials: AN
authors.lastname: Sheth
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine.|Grady Healthcare System.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Lennox
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta.
authors.forename: Andrea
authors.initials: A
authors.lastname: Knezevic
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta.
authors.forename: Laura
authors.initials: L
authors.lastname: Ward
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta.
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Easley
authors.affiliation: Grady Healthcare System.
authors.forename: Philip
authors.initials: P
authors.lastname: Powers
authors.affiliation: Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine.|Atlanta Department of Veterans Affairs Medical Center, Decatur, Georgia.
authors.forename: M Neale
authors.initials: MN
authors.lastname: Weitzmann
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control*; D012367:RNA, Viral / Q000097:blood; D000077211:Zoledronic Acid
chemical_list: D044966:Anti-Retroviral Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D012367:RNA, Viral; D000077211:Zoledronic Acid
keywords: antiretroviral therapy–induced bone loss; human immunodeficiency virus; zoledronic acid