title: Bone mineral density effects of randomized regimen and nucleoside reverse transcriptase inhibitor selection from ACTG A5142.
abstract: OBJECTIVE
  To compare the longitudinal changes in total bone mineral density (TBMD) across antiretroviral (ARV) regimens.
  
  
  METHODS
  A5142 was an open-label study comparing 3 ARV regimens for the initial treatment of HIV-1. Subjects were randomized equally to efavirenz (EFV) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs), lopinavir/ritonavir (LPV/r) plus 2 NRTIs, or LPV/r plus EFV without NRTI. The NRTI regimen (lamivudine [3TC] plus zidovudine [ZDV], stavudine [d4T], or tenofovir [TDF]) was selected prior to randomization. TBMD was assessed via whole-body dual-energy X-ray absorptiometry (DXA) at baseline and 48 and 96 weeks. Analysis was modified intent-to-treat (ITT) ignoring regimen changes using all evaluations.
  
  
  RESULTS
  Significant mean declines in TBMD at week 48 were observed among subjects. In repeated-measures analysis of changes (including randomized regimen, NRTI used, and time), there was a significant difference in the NRTI-containing arms in mean percentage change in TBMD at week 48 according to NRTI used (P < .001). Subjects taking ZDV had similar changes to those taking d4T (P = .970), whereas those taking TDF had larger declines (P < .001). There was a nonsignificant trend toward greater mean declines among subjects taking LPV/r versus EFV (P = .080). Overall, TDF-containing regimens demonstrated the greatest losses in TBMD, while EFV regimens without TDF had lesser TBMD reductions even compared to the NRTI-sparing arm. From week 48 to 96, all treatment groups continued to lose TBMD at similar rates.
  
  
  CONCLUSIONS
  Among NRTI-containing arms, NRTI selection, especially use of TDF, had a greater effect on TBMD change than randomized regimen. The long-term clinical significance remains to be demonstrated.
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, California.
authors.forename: Jeannie S
authors.initials: JS
authors.lastname: Huang
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hughes
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Riddler
authors.forename: Richard H
authors.initials: RH
authors.lastname: Haubrich
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology; D015519:Bone Density / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors
keywords: HIV; antiretroviral therapy; bone density