TY - JOUR
T1 - Hepatitis C Virus (HCV) direct-acting antiviral therapy in persons with human immunodeficiency virus-HCV genotype 1 coinfection resulting in high rate of sustained virologic response and variable in normalization of soluble markers of immune activation
AU - Anthony, Donald D.
AU - Sulkowski, Mark S.
AU - Smeaton, Laura M.
AU - Damjanovska, Sofi
AU - Shive, Carey L.
AU - Kowal, Corinne M.
AU - Cohen, Daniel E.
AU - Bhattacharya, Debika
AU - Alston-Smith, Beverly L.
AU - Balagopal, Ashwin
AU - Wyles, David L.
N1 - Funding Information:
This study was supported by AbbVie, the AIDS Clinical Trials Group (ACTG) under Award Numbers UM1 AI106701, UM1 AI068634, Statistical and Data Management Center (SDMC) for ACTG, IK2CX001471 (C. S. I.), BX001894 and CX001791 (D. D. A.), K24DA034621 (M. S. S.).
PY - 2020/10/15
Y1 - 2020/10/15
N2 - Background: Hepatitis C virus (HCV) direct-acting antivirals are highly effective. Less is known about changes in markers of immune activation in persons with human immunodeficiency virus (HIV) in whom a sustained virologic response (SVR) is achieved. Methods: We conducted a nonrandomized clinical trial of 12 or 24 weeks of paritaprevir-ritonavir-ombitasvir plus dasabuvir (PrOD) with or without ribavirin in persons with HCV-1/HIV coinfection suppressed with antiretroviral therapy. Plasma HCV, soluble CD14 (sCD14), interferon-inducible protein 10, soluble CD163 (sCD163), interleukin 6 (IL-6), interleukin 18, monocyte chemoattractant protein (MCP-1), autotaxin (ATX), and Mac2-binding protein (Mac2BP) were measured over 48 weeks. Results: Participants were treated with PrOD for 12 (n = 9) or 24 (n = 36) weeks; the SVR rate at 12 weeks was 93%. At baseline, cirrhosis was associated with higher ATX and MCP-1, female sex with higher ATX and IL-6, older age with higher Mac2BP, higher body mass index with higher ATX, and HIV-1 protease inhibitor use with higher sCD14 levels. In those with SVR, interferon-inducible protein 10, ATX, and Mac2BP levels declined by week 2, interleukin 18 levels declined by the end of treatment, sCD14 levels did not change, and sCD163, MCP-1, and IL-6 levels changed at a single time point. Conclusions: During HIV/HCV coinfection, plasma immune activation marker heterogeneity is in part attributable to age, sex, cirrhosis, body mass index, and/or type of antiretroviral therapy. HCV treatment with paritaprevir-ritonavir-ombitasvir plus dasabuvir is highly effective and is associated with variable rate and magnitude of decline in markers of immune activation.
AB - Background: Hepatitis C virus (HCV) direct-acting antivirals are highly effective. Less is known about changes in markers of immune activation in persons with human immunodeficiency virus (HIV) in whom a sustained virologic response (SVR) is achieved. Methods: We conducted a nonrandomized clinical trial of 12 or 24 weeks of paritaprevir-ritonavir-ombitasvir plus dasabuvir (PrOD) with or without ribavirin in persons with HCV-1/HIV coinfection suppressed with antiretroviral therapy. Plasma HCV, soluble CD14 (sCD14), interferon-inducible protein 10, soluble CD163 (sCD163), interleukin 6 (IL-6), interleukin 18, monocyte chemoattractant protein (MCP-1), autotaxin (ATX), and Mac2-binding protein (Mac2BP) were measured over 48 weeks. Results: Participants were treated with PrOD for 12 (n = 9) or 24 (n = 36) weeks; the SVR rate at 12 weeks was 93%. At baseline, cirrhosis was associated with higher ATX and MCP-1, female sex with higher ATX and IL-6, older age with higher Mac2BP, higher body mass index with higher ATX, and HIV-1 protease inhibitor use with higher sCD14 levels. In those with SVR, interferon-inducible protein 10, ATX, and Mac2BP levels declined by week 2, interleukin 18 levels declined by the end of treatment, sCD14 levels did not change, and sCD163, MCP-1, and IL-6 levels changed at a single time point. Conclusions: During HIV/HCV coinfection, plasma immune activation marker heterogeneity is in part attributable to age, sex, cirrhosis, body mass index, and/or type of antiretroviral therapy. HCV treatment with paritaprevir-ritonavir-ombitasvir plus dasabuvir is highly effective and is associated with variable rate and magnitude of decline in markers of immune activation.
KW - DAA therapy
KW - Hepatitis C
KW - Human
KW - Immunity
KW - Inflammation
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UR - http://www.scopus.com/inward/citedby.url?scp=85091126134&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiaa254
DO - 10.1093/infdis/jiaa254
M3 - Article
C2 - 32406487
AN - SCOPUS:85091126134
VL - 222
SP - 1334
EP - 1344
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 8
ER -