Complete manuscript Title: Changes in RANKL during the first two years after cART initiation in HIV-infected cART naïve adults

BMC Infect Dis. 2017 Apr 11;17(1):262. doi: 10.1186/s12879-017-2368-y.

Abstract

Background: By assessing the changes in concentration of soluble receptor activator of nuclear factor κ B ligand (RANKL) and osteoprotegrin (OPG) after initiation of combination antiretroviral therapy (cART) in treatment-naïve HIV-infected patients we aimed to evaluate whether the initial accelerated bone loss could be mediated by increased soluble RANKL (sRANKL) levels associated with CD4+ T cell recovery.

Methods: We used multiplex immunoassays to determine sRANKL and OPG concentrations in plasma from 48 HIV patients at baseline and 12, 24, 48 and 96 weeks after cART initiation.

Results: Soluble RANKL changed significantly over time (overall p = 0.02) with 25% decrease (95% CI: -42 to -5) at week 24 compared to baseline and stabilized at a lower level thereafter. We found no correlation between CD4+ T cell count increment and changes in sRANKL or between percentage change in BMD and changes in sRANKL.

Conclusion: In this study there was no indication that the accelerated bone loss after cART initiation was mediated by early changes in sRANKL due to CD4+ T cell recovery. Future studies should focus on the initial weeks after initiation of cART.

Trial registration: Clinical-Trial.gov . id NCT00135460 , August 25, 2005. The study was approved by the Danish Data Protection Agency, Danish Medicines Agency and Regional Ethics Committee.

Keywords: BMD; HIV infection; OPG; RANKL; cART.

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • CD4-Positive T-Lymphocytes
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / metabolism*
  • Humans
  • Lymphocyte Count
  • Male
  • Middle Aged
  • RANK Ligand / metabolism*

Substances

  • Anti-HIV Agents
  • RANK Ligand
  • TNFSF11 protein, human

Associated data

  • ClinicalTrials.gov/NCT00135460
  • ClinicalTrials.gov/NCT00135460