title: Comparison of bone and renal effects in HIV-infected adults switching to abacavir or tenofovir based therapy in a randomized trial.
abstract: BACKGROUND
  Our objective was to compare the bone and renal effects among HIV-infected patients randomized to abacavir or tenofovir-based combination anti-retroviral therapy.
  
  
  METHODS
  In an open-label randomized trial, HIV-infected patients were randomized to switch from zidovudine/lamivudine (AZT/3TC) to abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). We measured bone mass density (BMD) and bone turnover biomarkers (osteocalcin, osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), alkaline phosphatase, type I collagen cross-linked C-telopeptide (CTx), and osteoprotegerin). We assessed renal function by estimated creatinine clearance, plasma cystatin C, and urinary levels of creatinine, albumin, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL). The changes from baseline in BMD and renal and bone biomarkers were compared across study arms.
  
  
  RESULTS
  Of 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. BMD was measured in 33, 26, and 27 patients at baseline, week 24, and week 48, respectively. In TDF/FTC-treated patients we observed significant reductions from baseline in hip and lumbar spine BMD at week 24 (-1.8% and -2.5%) and week 48 (-2.1% and -2.1%), whereas BMD was stable in patients in the ABC/3TC arm. The changes from baseline in BMD were significantly different between study arms. All bone turnover biomarkers except osteoprotegerin increased in the TDF/FTC arm compared with the ABC/3TC arm, but early changes did not predict subsequent loss of BMD. Renal function parameters were similar between study arms although a small increase in NGAL was detected among TDF-treated patients.
  
  
  CONCLUSIONS
  Switching to TDF/FTC-based therapy led to decreases in BMD and increases in bone turnover markers compared with ABC/3TC-based treatment. No major difference in renal function was observed.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00647244.
authors.affiliation: Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark. thomrasm@rm.dk
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Rasmussen
authors.forename: Danny
authors.initials: D
authors.lastname: Jensen
authors.forename: Martin
authors.initials: M
authors.lastname: Tolstrup
authors.forename: Ulla S
authors.initials: US
authors.lastname: Nielsen
authors.forename: Erland J
authors.initials: EJ
authors.lastname: Erlandsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Birn
authors.forename: Lars
authors.initials: L
authors.lastname: Østergaard
authors.forename: Bente L
authors.initials: BL
authors.lastname: Langdahl
authors.forename: Alex L
authors.initials: AL
authors.lastname: Laursen
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D055316:Cystatin C / Q000097:blood / Q000652:urine; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000627:therapeutic use; D004338:Drug Combinations; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007677:Kidney Function Tests; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D015675:Osteocalcin / Q000097:blood; D000068698:Tenofovir; D013997:Time Factors; D016896:Treatment Outcome; D000099227:Abacavir
chemical_list: D000225:Adenine; D000469:Alkaline Phosphatase; D019380:Anti-HIV Agents; D015415:Biomarkers; D003404:Creatinine; D055316:Cystatin C; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D004338:Drug Combinations; D000068679:Emtricitabine; D019259:Lamivudine; D063065:Organophosphonates; D015675:Osteocalcin; D000068698:Tenofovir; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir