Vitamin D, D-dimer, Interferon γ, and sCD14 Levels are Independently Associated with Immune Reconstitution Inflammatory Syndrome: A Prospective, International Study.


Journal Article

To determine the immunological profile most important for IRIS prediction, we evaluated 20 baseline plasma biomarkers in Acquired Immunodeficiency Syndrome (AIDS) patients initiating antiretroviral therapy (ART). Patients were enrolled in a randomized, placebo-controlled ART initiation trial in South Africa and Mexico to test whether maraviroc could prevent IRIS. Participants were classified prospectively as having IRIS within 6 months of ART initiation. Twenty plasma biomarkers were measured at study enrollment for 267 participants. Biomarkers were tested for predicting IRIS with adjustment for covariates chosen through forward stepwise selection. Sixty-two participants developed IRIS and of these 19 were tuberculosis (TB)-IRIS. Baseline levels of vitamin D and higher d-dimer, interferon gamma (IFNγ), and sCD14 were independently associated with risk of IRIS in multivariate analyses. TB-IRIS cases exhibited a distinct biosignature from IRIS related to other pathogens, with increased levels of C-reactive protein (CRP), sCD14, IFNγ, and lower levels of Hb that could be captured by a composite risk score. Elevated markers of Type 1 T helper (Th1) response, monocyte activation, coagulation and low vitamin D were independently associated with IRIS risk. Interventions that decrease immune activation and increase vitamin D levels warrant further study.

Full Text

Cited Authors

  • Musselwhite, LW; Andrade, BB; Ellenberg, SS; Tierney, A; Belaunzaran-Zamudio, PF; Rupert, A; Lederman, MM; Sanne, I; Sierra Madero, JG; Sereti, I

Published Date

  • February 2016

Published In

Volume / Issue

  • 4 /

Start / End Page

  • 115 - 123

PubMed ID

  • 26981576

Pubmed Central ID

  • 26981576

Electronic International Standard Serial Number (EISSN)

  • 2352-3964

International Standard Serial Number (ISSN)

  • 2352-3964

Digital Object Identifier (DOI)

  • 10.1016/j.ebiom.2016.01.016


  • eng