title: Complete manuscript Title: Changes in RANKL during the first two years after cART initiation in HIV-infected cART naïve adults.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Inger Hee
authors.initials: IH
authors.lastname: Mathiesen
authors.affiliation: Department of Microbiology & Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Salem
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Julie Christine
authors.initials: JC
authors.lastname: Gaardbo
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Obel
authors.affiliation: Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
authors.forename: Court
authors.initials: C
authors.lastname: Pedersen
authors.affiliation: Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ullum
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Susanne Dam
authors.initials: SD
authors.lastname: Nielsen
authors.affiliation: Department of Infectious Diseases, Copenhagen University Hospital Hvidovre Hospital, Kettegaard Allé 30, -2650, Copenhagen, DK, Denmark. ann-brit.eg.hansen.02@regionh.dk.
authors.forename: Ann-Brit Eg
authors.initials: AE
authors.lastname: Hansen
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D053245:RANK Ligand / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D053245:RANK Ligand; C505688:TNFSF11 protein, human
keywords: BMD; HIV infection; OPG; RANKL; cART