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

Inger Hee Mathiesen, Mohammad Salem, Jan Gerstoft, Julie Christine Gaardbo, Niels Obel, Court Pedersen, Henrik Ullum, Susanne Dam Nielsen, Ann-Brit Eg Hansen, Inger Hee Mathiesen, Mohammad Salem, Jan Gerstoft, Julie Christine Gaardbo, Niels Obel, Court Pedersen, Henrik Ullum, Susanne Dam Nielsen, Ann-Brit Eg Hansen

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.

Figures

Fig. 1
Fig. 1
Overall mean RANKL, OPG and RANKL/OPG ratio. Mean levels (95% CI) of (1a) RANKL, (1b) OPG and (1c) RANKL/OPG ratio. Data are logarithmically transformed. 1 unit change in log2 unit corresponds to a doubling in original unit. *p < 0.05 compared to baseline value

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Source: PubMed

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