title: Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study.
abstract: BACKGROUND
  Abacavir-lamivudine and tenofovir DF-emtricitabine fixed-dose combinations are commonly used as first-line antiretroviral therapies. However, few studies have comprehensively compared their relative safety profiles.
  
  
  METHODS
  In this European, multicenter, open-label, 96-week study, antiretroviral-naive adult subjects with human immunodeficiency virus (HIV) infection were randomized to receive either abacavir-lamivudine or tenofovir-emtricitabine with efavirenz. Primary analyses were conducted after 48 weeks of treatment. Bone mineral density (BMD), a powered secondary end point, was assessed by dual energy x-ray absorptiometry. Bone turnover markers (osteocalcin, procollagen 1 N-terminal propeptide, bone specific alkaline phosphatase, and type 1 collagen cross-linked C telopeptide [CTx]) were assessed in an exploratory analysis.
  
  
  RESULTS
  A total of 385 subjects were enrolled in the study. BMD loss was observed in both treatment groups, with a significant difference in the change from baseline in both total hip (abacavir-lamivudine group, -1.9%; tenofovir-emtricitabine group, -3.6%; P < .001) and lumbar spine (abacavir-lamivudine group, -1.6%; tenofovir-emtricitabine group, -2.4%; P = .036). BMD loss of >or=6% was more common in the tenofovir-emtricitabine group (13% of the tenofovir-emtricitabine group vs 3% of the abacavir-lamivudine group had a loss of >or=6% in the hip; 15% vs 5% had a loss of >or=6% in the spine). Bone turnover markers increased in both treatment groups over the first 24 weeks, stabilizing or decreasing thereafter. Increases in all markers were significantly greater in the tenofovir-emtricitabine treatment group than in the abacavir-lamivudine group at week 24. All but CTx remained significantly different at week 48 (eg, osteocalcin: abacavir-lamivudine group, +8.07 mg/L; tenofovir-emtricitabine group, +11.92 mg/L; P < .001).
  
  
  CONCLUSIONS
  This study demonstrated the impact of first-line treatment regimens on bone. Greater increases in bone turnover and decreases in BMD were observed in subjects treated with tenofovir-emtricitabine than were observed in subjects treated with abacavir-lamivudine.
authors.affiliation: Infektions Medizinisches Centrum Hamburg Study Center, Hamburg, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Stellbrink
authors.forename: Chloe
authors.initials: C
authors.lastname: Orkin
authors.forename: Jose Ramon
authors.initials: JR
authors.lastname: Arribas
authors.forename: Juliet
authors.initials: J
authors.lastname: Compston
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.forename: Eric
authors.initials: E
authors.lastname: Van Wijngaerden
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.forename: Giuliano
authors.initials: G
authors.lastname: Rizzardini
authors.forename: Herman G
authors.initials: HG
authors.lastname: Sprenger
authors.forename: John
authors.initials: J
authors.lastname: Lambert
authors.forename: Gunta
authors.initials: G
authors.lastname: Sture
authors.forename: David
authors.initials: D
authors.lastname: Leather
authors.forename: Sara
authors.initials: S
authors.lastname: Hughes
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zucchi
authors.forename: Helen
authors.initials: H
authors.lastname: Pearce
mesh_terms: D015502:Absorptiometry, Photon; D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology*; D001842:Bone and Bones / Q000473:pathology / Q000503:physiopathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000009:adverse effects*; D004338:Drug Combinations; D000068679:Emtricitabine; D005060:Europe; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D000068698:Tenofovir; D055815:Young Adult; D000099227:Abacavir
chemical_list: D000225:Adenine; D019380:Anti-HIV Agents; D003841:Deoxycytidine; D015224:Dideoxynucleosides; D004338:Drug Combinations; D000068679:Emtricitabine; D019259:Lamivudine; D063065:Organophosphonates; D000068698:Tenofovir; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir