TY - JOUR
T1 - Vitamin D does not modulate immune-mediated bone loss during ART initiation
AU - the A5280 Study Team
AU - Yin, Michael T.
AU - Chan, Ellen S.
AU - Brown, Todd T.
AU - Kinslow, Jennifer
AU - Martinson, Jeffrey
AU - Landay, Alan
AU - Melbourne, Kathleen M.
AU - Ribaudo, Heather J.
AU - Overton, Edgar T.
N1 - Funding Information:
Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636 and UM1 AI106701 and supported by National Institute of Mental Health (NIMH), National Institute of Dental and Craniofacial Research (NIDCR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health, Bristol-Myers Squibb and Gilead funded the DXA scans and ancillary laboratory testing. Study medications were provided by Bristol-Myers Squibb, Gilead Sciences and Tischcon Corporation.
Funding Information:
We wish to gratefully acknowledge all of the study sites and study participants who have devoted their time and effort to this research endeavor. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636 and UM1 AI106701 and supported by National Institute of Mental Health (NIMH), National Institute of Dental and Craniofacial Research (NIDCR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health, Bristol-Myers Squibb and Gilead funded the DXA scans and ancillary laboratory testing. Study medications were provided by Bristol-Myers Squibb, Gilead Sciences and Tischcon Corporation. This work was presented at the International AIDS Society Conference on 24–27 July 2018 in Amsterdam, the Netherlands. Abstract number TUPEB112. Trial registration number: NCT01403051.
Publisher Copyright:
©2019 International Medical Press.
PY - 2019
Y1 - 2019
N2 - Background: Vitamin D (VitD) and calcium (Ca) supplementation attenuates antiretroviral therapy (ART)-associated bone loss, but it is unclear whether this effect is mediated through immunomodulation. Methods: In this exploratory analysis of A5280, a 48-week, randomized, double-blind, placebo-controlled study of VitD/Ca supplementation with ART initiation, we characterized lymphocyte phenotypes and receptor activator of nuclear factor kappa-B ligand (RANKL) expression by median fluorescence intensity (MFI) at baseline and 48 weeks. Changes were evaluated within and between treatment groups by Wilcoxon signed rank and rank sum tests, respectively. Spearman correlations estimated relationships between cellular phenotypes and bone mineral density (BMD). Results: Of 165 participants enrolled, 138 had samples for cellular phenotypes (64 VitD/Ca, 74 placebo). Markers of CD4, CD8 activation (CD38+HLA-DR+) declined (all P<0.001), but did not differ between arms. There was no decline in either %T-cells (CD4 and CD8) expressing RANKL or expression of RANKL by MFI. CD4 and CD8 activation markers were not correlated with BMD at baseline (r<0.15 and P>0.09 for all), but greater declines in CD4 activation correlated with greater declines in hip and spine BMD in both arms (0.25 ≤r ≤0.37, all P<0.05). A greater decline in CD8 activation was correlated with greater declines in both hip and spine BMD in the placebo arm only (hip r=0.31, P=0.009; spine r=0.25, P=0.035). Conclusions: Reductions in T-cell activation are characteristic of ART initiation, but only correlated modestly with bone loss. VitD/Ca supplementation does not appear to mitigate bone loss through modulation of immune activation or expression of RANKL. Trial registration number: NCT01403051.
AB - Background: Vitamin D (VitD) and calcium (Ca) supplementation attenuates antiretroviral therapy (ART)-associated bone loss, but it is unclear whether this effect is mediated through immunomodulation. Methods: In this exploratory analysis of A5280, a 48-week, randomized, double-blind, placebo-controlled study of VitD/Ca supplementation with ART initiation, we characterized lymphocyte phenotypes and receptor activator of nuclear factor kappa-B ligand (RANKL) expression by median fluorescence intensity (MFI) at baseline and 48 weeks. Changes were evaluated within and between treatment groups by Wilcoxon signed rank and rank sum tests, respectively. Spearman correlations estimated relationships between cellular phenotypes and bone mineral density (BMD). Results: Of 165 participants enrolled, 138 had samples for cellular phenotypes (64 VitD/Ca, 74 placebo). Markers of CD4, CD8 activation (CD38+HLA-DR+) declined (all P<0.001), but did not differ between arms. There was no decline in either %T-cells (CD4 and CD8) expressing RANKL or expression of RANKL by MFI. CD4 and CD8 activation markers were not correlated with BMD at baseline (r<0.15 and P>0.09 for all), but greater declines in CD4 activation correlated with greater declines in hip and spine BMD in both arms (0.25 ≤r ≤0.37, all P<0.05). A greater decline in CD8 activation was correlated with greater declines in both hip and spine BMD in the placebo arm only (hip r=0.31, P=0.009; spine r=0.25, P=0.035). Conclusions: Reductions in T-cell activation are characteristic of ART initiation, but only correlated modestly with bone loss. VitD/Ca supplementation does not appear to mitigate bone loss through modulation of immune activation or expression of RANKL. Trial registration number: NCT01403051.
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U2 - 10.3851/IMP3316
DO - 10.3851/IMP3316
M3 - Article
C2 - 31085814
AN - SCOPUS:85076062157
SN - 1359-6535
VL - 24
SP - 355
EP - 362
JO - Antiviral therapy
JF - Antiviral therapy
IS - 5
ER -