Associations of T cell activation and inflammatory biomarkers with virological response to darunavir/ritonavir plus raltegravir therapy

Babafemi Taiwo*, Roy M. Matining, Lu Zheng, Michael M. Lederman, Charles R. Rinaldo, Peter S. Kim, Baiba I. Berzins, Daniel R. Kuritzkes, Amy Jennings, Joseph J. Eron, Cara C. Wilson

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Objectives: One of the goals of antiretroviral therapy (ART) is to attenuate HIV-induced systemic immune activation and inflammation. We determined the dynamics of biomarkers of immune activation, microbial translocation and inflammation during initial ART with a nucleos(t)ide-sparing regimen of darunavir/ritonavir plus raltegravir. We also evaluated associations between these biomarkers and the virological response to the regimen. Methods: We determined baseline and week 24 and 48 levels of CD4+ and CD8+ Tcell activation (% HLA-DR+/ CD38+), interleukin-6 (IL-6), interferon-g-inducible protein-10 (IP-10), soluble CD14 (sCD14), D-dimer and lipo-polysaccharide. Associations between the biomarkers at baseline were assessed using Spearman's rank correlation. The Wilcoxon signed rank test analysed changes from baseline. Comparisons between groups were made using the Wilcoxon rank sum test, and Cox proportional hazards models assessed predictors of virological failure (VF). Results: Assays were completed on 107 of 112 subjects after excluding five subjects who had only baseline samples. The subjects included were 94 (88%) men with a median age of 37 years, a median baseline CD4 count of 261.5 cells/mm3 and a median baseline viral load (VL) of 75 876 copies/mL. Subjects with a baseline VL >100000 copies/mL had higher baseline T cell activation, IL-6, IP-10, sCD14 and D-dimer. These biomarkers declined during treatment (P≤0.05). Although subjects who experienced VF had higher baseline CD4+ T cell activation (P1=40.035), only baseline VL independently predicted VF (hazard ratio for .100000 versus >100000 copies/mL was 4.5-5.6, P≤0.002). Conclusions: Darunavir/ritonavir plus raltegravir attenuated immune activation, inflammation and microbial translocation. T cell activation remained higher in subjects with VF than those without. Baseline VL .100000 copies/mL remained the primary driver of VF.

Original languageEnglish (US)
Article numberdkt120
Pages (from-to)1857-1861
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume68
Issue number8
DOIs
StatePublished - Aug 2013

Keywords

  • Microbial translocation
  • Nucleos(t)ide sparing
  • Soluble CD14

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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    Taiwo, B., Matining, R. M., Zheng, L., Lederman, M. M., Rinaldo, C. R., Kim, P. S., Berzins, B. I., Kuritzkes, D. R., Jennings, A., Eron, J. J., & Wilson, C. C. (2013). Associations of T cell activation and inflammatory biomarkers with virological response to darunavir/ritonavir plus raltegravir therapy. Journal of Antimicrobial Chemotherapy, 68(8), 1857-1861. [dkt120]. https://doi.org/10.1093/jac/dkt120