S Hattab1,2, M Guiguet1,2, G Carcelain3,4,5, S Fourati1,2,6, A Guihot3,4,5, B Autran3,4,5, F Caby1,7, A-G Marcelin1,2,6, D Costagliola1,2, C Katlama1,2,7. 1. UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, INSERM, Paris, France. 2. UPMC Univ Paris 06, UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, Sorbonne Universities, Paris, France. 3. UMR_S 1135, CIMI, INSERM, Paris, France. 4. UPMC Univ Paris 06, UMR_S 1135, CIMI, Sorbonne Universities, Paris, France. 5. Immunology Department, Pitié-Salpêtrière Hospital, AP-HP, Paris, France. 6. Virology Department, Pitié-Salpêtrière Hospital, AP-HP, Paris, France. 7. Pitié-Salpêtrière Hospital, Infectious Diseases Department, AP-HP, Paris, France.
Abstract
OBJECTIVES: The aim of the study was to assess the impact of rapid and sustained viral control produced by combination antiretroviral therapy (cART) on HIV-associated immune activation and inflammation. METHODS: In this longitudinal observational study, we examined changes in interleukin-6 (IL-6), interferon-γ-inducible protein-10 (IP-10), monokine induced by interferon-γ (MIG) and soluble CD14 (sCD14) levels during 2 years of effective first-line cART. Biomarker levels before and after cART were compared with those observed in healthy subjects, using the Wilcoxon signed rank test. Elevated biomarker levels were defined with respect to values for healthy subject (mean + 2 standard deviations). Factors associated with persistently elevated biomarker levels after 2 years of cART were identified by logistic regression. RESULTS: We included in the study 139 patients with a median HIV-1 RNA level of 4.8 log10 HIV-1 RNA copies/mL and a median CD4 cell count of 294 cells/μL at cART initiation [day 0 (D0)]. At D0, all biomarker levels were higher than in healthy subjects (P < 0.05). After 2 years of cART, IL-6, IP-10 and MIG levels fell significantly, by a median of 0.54, 420 and 1107 pg/mL, respectively (all P < 0.001), and were no longer elevated in > 75% of patients. In contrast, sCD14 levels did not change significantly (0.18 × 10(6) pg/mL; P = 0.102) and remained elevated. Older age was associated with elevated levels of IP-10 [odds ratio (OR) 1.60 per 10 years older; P = 0.047] and MIG (OR 1.92 per 10 years older; P = 0.007) after 2 years of cART. CONCLUSIONS: The rapid and sustained viral suppression produced by first-line cART reduced IL-6, IP-10 and MIG to normal levels, while sCD14, a marker of monocyte activation, remained elevated. High levels of IP-10 and MIG tended to persist in older patients.
OBJECTIVES: The aim of the study was to assess the impact of rapid and sustained viral control produced by combination antiretroviral therapy (cART) on HIV-associated immune activation and inflammation. METHODS: In this longitudinal observational study, we examined changes in interleukin-6 (IL-6), interferon-γ-inducible protein-10 (IP-10), monokine induced by interferon-γ (MIG) and soluble CD14 (sCD14) levels during 2 years of effective first-line cART. Biomarker levels before and after cART were compared with those observed in healthy subjects, using the Wilcoxon signed rank test. Elevated biomarker levels were defined with respect to values for healthy subject (mean + 2 standard deviations). Factors associated with persistently elevated biomarker levels after 2 years of cART were identified by logistic regression. RESULTS: We included in the study 139 patients with a median HIV-1 RNA level of 4.8 log10 HIV-1 RNA copies/mL and a median CD4 cell count of 294 cells/μL at cART initiation [day 0 (D0)]. At D0, all biomarker levels were higher than in healthy subjects (P < 0.05). After 2 years of cART, IL-6, IP-10 and MIG levels fell significantly, by a median of 0.54, 420 and 1107 pg/mL, respectively (all P < 0.001), and were no longer elevated in > 75% of patients. In contrast, sCD14 levels did not change significantly (0.18 × 10(6) pg/mL; P = 0.102) and remained elevated. Older age was associated with elevated levels of IP-10 [odds ratio (OR) 1.60 per 10 years older; P = 0.047] and MIG (OR 1.92 per 10 years older; P = 0.007) after 2 years of cART. CONCLUSIONS: The rapid and sustained viral suppression produced by first-line cART reduced IL-6, IP-10 and MIG to normal levels, while sCD14, a marker of monocyte activation, remained elevated. High levels of IP-10 and MIG tended to persist in older patients.
Authors: Sofie Jespersen; Karin Kæreby Pedersen; Birgitta Anesten; Henrik Zetterberg; Dietmar Fuchs; Magnus Gisslén; Lars Hagberg; Marius Trøseid; Susanne Dam Nielsen Journal: BMC Infect Dis Date: 2016-04-21 Impact factor: 3.090
Authors: Chanelle M Diaz; Eddy R Segura; Paula M Luz; Jesse L Clark; Sayonara R Ribeiro; Raquel De Boni; Leonardo Eksterman; Rodrigo Moreira; Judith S Currier; Valdiléa G Veloso; Beatriz Grinsztejn; Jordan E Lake Journal: BMC Infect Dis Date: 2016-08-08 Impact factor: 3.090
Authors: Ashwin Balagopal; Nikhil Gupte; Rupak Shivakoti; Andrea L Cox; Wei-Teng Yang; Sima Berendes; Noluthando Mwelase; Cecilia Kanyama; Sandy Pillay; Wadzanai Samaneka; Breno Santos; Selvamuthu Poongulali; Srikanth Tripathy; Cynthia Riviere; Javier R Lama; Sandra W Cardoso; Patcharaphan Sugandhavesa; Richard D Semba; James Hakim; Mina C Hosseinipour; Nagalingeswaran Kumarasamy; Ian Sanne; David Asmuth; Thomas Campbell; Robert C Bollinger; Amita Gupta Journal: Open Forum Infect Dis Date: 2016-07-27 Impact factor: 3.835
Authors: Alinda G Vos; Caitlin N Dodd; Eveline M Delemarre; Stefan Nierkens; Celicia Serenata; Diederick E Grobbee; Kerstin Klipstein-Grobusch; W D Francois Venter Journal: Front Immunol Date: 2021-07-05 Impact factor: 7.561
Authors: Adam Trickey; Margaret T May; Philipp Schommers; Jan Tate; Suzanne M Ingle; Jodie L Guest; M John Gill; Robert Zangerle; Mike Saag; Peter Reiss; Antonella d'Arminio Monforte; Margaret Johnson; Viviane D Lima; Tim R Sterling; Matthias Cavassini; Linda Wittkop; Dominique Costagliola; Jonathan A C Sterne Journal: Clin Infect Dis Date: 2017-09-15 Impact factor: 9.079