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

TitleAssociations of T cell activation and inflammatory biomarkers with virological response to darunavir/ritonavir plus raltegravir therapy.
Publication TypeJournal Article
Year of Publication2013
AuthorsTaiwo B, Matining RM, Zheng L, Lederman MM, Rinaldo CR, Kim PS, Berzins BI, Kuritzkes DR, Jennings A, Eron JJ, Wilson CC
JournalJ Antimicrob Chemother
Volume68
Issue8
Pagination1857-61
Date Published2013 Aug
ISSN1460-2091
KeywordsAdult, Anti-HIV Agents, Biomarkers, Darunavir, Female, HIV Infections, Humans, Immunophenotyping, Lymphocyte Activation, Male, Pyrrolidinones, Raltegravir Potassium, Ritonavir, Sulfonamides, T-Lymphocytes, Viral Load
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+ T cell activation (% HLA-DR+/CD38+), interleukin-6 (IL-6), interferon-γ-inducible protein-10 (IP-10), soluble CD14 (sCD14), D-dimer and lipopolysaccharide. 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/mm(3) and a median baseline viral load (VL) of 75 876 copies/mL. Subjects with a baseline VL >100 000 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 (P = 0.035), only baseline VL independently predicted VF (hazard ratio for >100 000 versus ≤100 000 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 >100 000 copies/mL remained the primary driver of VF.

DOI10.1093/jac/dkt120
Alternate JournalJ. Antimicrob. Chemother.
PubMed ID23599363
PubMed Central IDPMC3716396
Grant ListP30 AI050410 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
U01AI68634 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI069423 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI069471 / AI / NIAID NIH HHS / United States