Changes in Inflammation and Immune Activation with Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy: ACTG 5260s

Theodoros Kelesidis, Thuy Tien T. Tran, James H. Stein, Todd T. Brown, Carlee Moser, Heather J. Ribaudo, Michael P. Dube, Robert Murphy, Otto O. Yang, Judith S. Currier, Grace A. McComsey*

*Corresponding author for this work

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Background. It is unclear whether the integrase inhibitor raltegravir (RAL) reduces inflammation and immune activation compared with ritonavir-boosted protease inhibitors (PIs). Methods. In a prospective, randomized, multicenter clinical trial that included 328 human immunodeficiency type 1 (HIV-1)-infected, treatment-naive participants were randomized to receive tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or RAL. A total of 234 participants (71%) with HIV-1 RNA levels <50 copies/mL by week 24 were included. Plasma biomarkers of inflammation and coagulation that were analysed included high-sensitivity C-reactive protein, interleukin-6 (IL-6), GlycA, D-dimer, soluble CD14 (sCD14), sCD163, and sIL-2r; blood cellular markers included %CD38+DR+ of T-cell subsets and %CD14+CD16+ and%CD14(dim)CD16+ monocyte subsets. Changes from baseline were examined at earlier (24 or 48 weeks) and later (96 weeks) time points, with 95% confidence intervals on fold-change. Pairwise treatment groups were compared using Wilcoxon rank sum tests, with P values adjusted for false discovery rate control. Results. Changes in biomarkers varied by regimen during the 96 weeks of follow-up as follows: hsCRP declined with ATV/r and RAL, IL-6 declined only with RAL, and GLycA decreased in all groups. D-dimer declined with ATV/r and DRV/r and was unchanged with RAL. Markers of T-cell activation and sCD163 (but not sCD14 and CD14-+CD16+) declined in all groups. Conclusions. Despite some differences in specific markers of inflammation and immune activation between the antiretroviral therapy (ART) regimens, we found no consistent evidence that the reduction of inflammation and immune activation with ART initiation was different between RAL and PI-based regimens.

Original languageEnglish (US)
Pages (from-to)651-660
Number of pages10
JournalClinical Infectious Diseases
Volume61
Issue number4
DOIs
StatePublished - Aug 15 2015

Keywords

  • human immunodeficiency virus
  • immune activation
  • inflammation
  • integrase inhibitors
  • protease inhibitors

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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    Kelesidis, T., Tran, T. T. T., Stein, J. H., Brown, T. T., Moser, C., Ribaudo, H. J., Dube, M. P., Murphy, R., Yang, O. O., Currier, J. S., & McComsey, G. A. (2015). Changes in Inflammation and Immune Activation with Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy: ACTG 5260s. Clinical Infectious Diseases, 61(4), 651-660. https://doi.org/10.1093/cid/civ327