Bone mineral density and fractures in antiretroviral-naive persons randomized to receive abacavir-lamivudine or tenofovir disoproxil fumarate-emtricitabine along with efavirenz or atazanavir-ritonavir: Aids Clinical Trials Group A5224s, a substudy of ACTG A5202

J Infect Dis. 2011 Jun 15;203(12):1791-801. doi: 10.1093/infdis/jir188.

Abstract

Background: Long-term effects of abacavir (ABC)-lamivudine (3TC), compared with tenofovir (TDF)-emtricitabine (FTC) with efavirenz (EFV) or atazanavir plus ritonavir (ATV/r), on bone mineral density (BMD) have not been analyzed.

Methods: A5224s was a substudy of A5202, in which HIV-infected treatment-naive participants were randomized and blinded to receive ABC-3TC or TDF-FTC with open-label EFV or ATV/r. Primary bone end points included Dual-emission X-ray absorbtiometry (DXA)-measured percent changes in spine and hip BMD at week 96. Primary analyses were intent-to-treat. Statistical tests used the factorial design and included linear regression, 2-sample t, log-rank, and Fisher's exact tests.

Results: Two hundred sixty-nine persons randomized to 4 arms of ABC-3TC or TDF-FTC with EFV or ATV/r. At baseline, 85% were male, and 47% were white non-Hispanic; the median HIV-1 RNA load was 4.6 log(10) copies/mL, the median age was 38 years, the median weight was 76 kg, and the median CD4 cell count was 233 cells/μL. At week 96, the mean percentage changes from baseline in spine and hip BMD for ABC-3TC versus TDF-FTC were -1.3% and -3.3% (P = .004) and -2.6% and -4.0% (P = .024), respectively; and for EFV versus ATV/r were -1.7% and -3.1% (P = .035) and -3.1% and -3.4% (P = .61), respectively. Bone fracture was observed in 5.6% of participants. The probability of bone fractures and time to first fracture were not different across components.

Conclusions: Compared with ABC-3TC, TDF-FTC-treated participants had significantly greater decreases in spine and hip BMD, whereas ATV/r led to more significant losses in spine, but not hip, BMD than EFV. Clinical Trials Registration. NCT00118898.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Adenine / adverse effects
  • Adenine / analogs & derivatives
  • Adult
  • Anti-HIV Agents / adverse effects*
  • Antiretroviral Therapy, Highly Active / adverse effects
  • Atazanavir Sulfate
  • Benzoxazines / adverse effects
  • Bone Density / drug effects*
  • CD4 Lymphocyte Count
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Dideoxynucleosides / adverse effects
  • Drug Combinations
  • Drug Therapy, Combination
  • Emtricitabine
  • Female
  • Fractures, Bone / chemically induced*
  • Fractures, Bone / epidemiology
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • Humans
  • Intention to Treat Analysis
  • Lamivudine / adverse effects
  • Male
  • Middle Aged
  • Oligopeptides / adverse effects
  • Organophosphonates / adverse effects
  • Osteoporosis / chemically induced*
  • Pyridines / adverse effects
  • Risk Factors
  • Ritonavir / adverse effects
  • Tenofovir
  • Viral Load

Substances

  • Anti-HIV Agents
  • Benzoxazines
  • Dideoxynucleosides
  • Drug Combinations
  • Oligopeptides
  • Organophosphonates
  • Pyridines
  • abacavir, lamivudine drug combination
  • Deoxycytidine
  • Lamivudine
  • Atazanavir Sulfate
  • Tenofovir
  • Emtricitabine
  • Adenine
  • efavirenz
  • Ritonavir

Associated data

  • ClinicalTrials.gov/NCT00118898