TY - JOUR
T1 - Associations of T cell activation and inflammatory biomarkers with virological response to darunavir/ritonavir plus raltegravir therapy
AU - Taiwo, Babafemi
AU - Matining, Roy M.
AU - Zheng, Lu
AU - Lederman, Michael M.
AU - Rinaldo, Charles R.
AU - Kim, Peter S.
AU - Berzins, Baiba I.
AU - Kuritzkes, Daniel R.
AU - Jennings, Amy
AU - Eron, Joseph J.
AU - Wilson, Cara C.
N1 - Funding Information:
Awards U01AI068636 and U01AI68634 from the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health (NIMH) and the National Institute of Dental and Craniofacial Research (NIDCR) supported this study. The study was also supported in part by grants funded by the National Center for Research Resources. Merck provided raltegravir and Janssen Therapeutics provided darunavir.
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
KW - Microbial translocation
KW - Nucleos(t)ide sparing
KW - Soluble CD14
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U2 - 10.1093/jac/dkt120
DO - 10.1093/jac/dkt120
M3 - Article
C2 - 23599363
AN - SCOPUS:84880743893
SN - 0305-7453
VL - 68
SP - 1857
EP - 1861
JO - Journal of antimicrobial chemotherapy
JF - Journal of antimicrobial chemotherapy
IS - 8
M1 - dkt120
ER -
