Increased bone resorption during tenofovir plus lopinavir/ritonavir therapy in Chinese individuals with HIV

Osteoporos Int. 2015 Mar;26(3):1035-44. doi: 10.1007/s00198-014-2874-3. Epub 2014 Sep 16.

Abstract

We sought to evaluate the effects of antiretroviral therapy on skeletal metabolism in Chinese individuals with human immunodeficiency virus. Patients switched to tenofovir/lamivudine + lopinavir/ritonavir after treatment failure had an increase in bone resorption marker levels by nearly 60%, which is greater than the magnitude previously described in non-Chinese populations.

Introduction: Few studies have evaluated the effects of antiretroviral therapy on skeletal metabolism in Asian populations infected with human immunodeficiency virus (HIV).

Methods: We performed a secondary analysis of bone turnover markers (BTM) at baseline and 2 years in stored plasma samples collected from 2/2009 to 1/2013 as part of a multi-center trial. Two groups were compared: (1) treatment-naïve patients initiated on zidovudine (AZT)/lamivudine (3TC) plus nevirapine (NVP) and (2) patients who failed first-line therapy and were switched to tenofovir (TDF)/3TC plus lopinavir/ritonavir (LPVr). Tests included the bone resorption marker, C-terminal cross-linking telopeptide of type-1 collagen (CTX), and the bone formation marker procollagen type 1 N-terminal propeptide (P1NP).

Results: In the TDF/3TC + LPVr group, samples were available from 59 patients at baseline and 56 patients at 2 years. Of these, 36 patients had samples available from both time points. In the AZT/3TC + NVP group, plasma samples were analyzed from 82 participants at baseline and of those, 61 had samples at 2 years. Median change over 2 years was greater in the TDF/3TC + LPVr group for both CTX (+0.24 ng/mL, interquartile ranges (IQR) 0.10-0.43 vs. +0.09 ng/mL, IQR -0.03 to 0.18, p = 0.001) and P1NP (+25.5 ng/mL, IQR 2.4-51.3 vs. +7.11 ng/mL, IQR -4.3 to 21.6, p = 0.012). Differences remained after adjusting for potential confounders in the multivariable analysis.

Conclusions: Switching to TDF/3TC + LPVr after treatment failure resulted in greater increases in BTMs than initiation with AZT/3TC + NVP in Chinese patients with HIV. Following this change, bone resorption marker levels increased by nearly 60 %, which is greater than the 25-35% increase from baseline described previously in non-Chinese populations. Further studies are warranted to elucidate these findings.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Biomarkers / blood
  • Bone Remodeling / drug effects
  • Bone Resorption / blood
  • Bone Resorption / chemically induced*
  • Collagen Type I / blood
  • Drug Combinations
  • Drug Substitution
  • Drug Therapy, Combination
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV-1*
  • Humans
  • Lopinavir / adverse effects*
  • Lopinavir / therapeutic use
  • Male
  • Middle Aged
  • Peptides / blood
  • Ritonavir / adverse effects*
  • Ritonavir / therapeutic use
  • Tenofovir / adverse effects*
  • Tenofovir / therapeutic use
  • Young Adult

Substances

  • Anti-HIV Agents
  • Biomarkers
  • Collagen Type I
  • Drug Combinations
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • lopinavir-ritonavir drug combination
  • Lopinavir
  • Tenofovir
  • Ritonavir