Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients

AIDS. 2009 Apr 27;23(7):817-24. doi: 10.1097/QAD.0b013e328328f789.

Abstract

Objective: To evaluate the change in bone mineral density (BMD) at specific sites in patients initiating antiretroviral therapy in a substudy of the ANRS 121 trial.

Methods: Antiretroviral-naive patients were randomized (2: 1: 1) into three treatment strategy arms: a nonnucleoside reverse transcriptase inhibitor (NNRTI) and a boosted protease inhibitor (PI/r), a PI/r and two nucleoside reverse transcriptase inhibitors (NRTIs) or an NNRTI and NRTIs. Hip and lumbar spine standardized BMD were evaluated at baseline and week 48 by dual X-ray absorptiometry by a central reading laboratory.

Results: Seventy-one patients were enrolled: 36 in the PI/r and NNRTI, 19 in the PI/r and NRTIs and 16 in the NNRTI and NRTIs arms. Baseline characteristics were [median (interquartile range)]: male (77%), age 40 years (33-49), 69% white, 58% smokers, BMI 23 kg/m2 (21-24), CD4 cell count 219 cells/microl (144-285). In the arms with NRTIs, 86% of patients received zidovudine/lamivudine. At baseline, 31% had osteopenia and 3% had osteoporosis. At week 48, there was a mean change in BMD of -4.1 +/- 3.9% at lumbar spine and -2.8 +/- 4.7% at hip (both P< or = 0.001). The decrease of BMD at lumbar spine was significantly worse in the PI/r and NNRTI arm (-4.4 +/- 3.4%) and in the PI/r and NRTIs arm (-5.8 +/- 4.5%) compared with the NNRTI and NRTIs arm (-1.5 +/- 2.9%), P = 0.007 and P = 0.001, respectively.

Conclusion: BMD was impaired in 34% of patients, before starting any antiretrovirals. After 1 year, the decrease in lumbar spine BMD was more pronounced in patients receiving either PI/r-containing regimen compared with NNRTI and NRTIs. BMD at specific sites should be monitored during lifelong antiretroviral therapy.

Trial registration: ClinicalTrials.gov NCT00122668.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bone Density / drug effects*
  • Bone Density / physiology
  • Bone Diseases, Metabolic / chemically induced*
  • Bone Diseases, Metabolic / physiopathology
  • CD4 Lymphocyte Count
  • Drug Administration Schedule
  • Female
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / adverse effects*
  • HIV-1*
  • Humans
  • Lumbar Vertebrae / drug effects*
  • Lumbar Vertebrae / physiopathology
  • Male
  • Middle Aged
  • Reverse Transcriptase Inhibitors / adverse effects*
  • Viral Load

Substances

  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors

Associated data

  • ClinicalTrials.gov/NCT00122668