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

Abstract

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.

Clinical trials registration: NCT02194998.

Keywords: DAA therapy; hepatitis C; human; immunity; inflammation.

Published by Oxford University Press for the Infectious Diseases Society of America 2020.

Figures

Figure 1.

Study design and cohort retention, showing study group distribution and cohort retention for the enrolled study participants. Abbreviations: DAAs, direct-acting antivirals; HCV, hepatitis C virus; INSTI, integrase strand-transfer inhibitor; PI, protease inhibitor; SVR12, sustained virologic response at 12 weeks; and SVR24, sustained virologic response at 24 weeks.

Figure 2.

Heterogeneity in markers of inflammation (by cirrhosis state and sex) at baseline and over the course of direct-acting antiviral (DAA) therapy. Left panels show inflammatory marker levels (median, interquartile range, and 5%/95% confidence intervals [CIs]) for all study participants as horizontal bar, box, and whiskers; x-axis labels represent time (weeks) from start of therapy, regardless of study arm or treatment duration. Middle panels show inflammatory marker levels for participants with sustained virologic response (SVR) by cirrhosis status (mean with 95% CI); x-axis labels indicate the times of sampling during and after therapy, with sample numbers indicated in insets. Right panels show inflammatory marker levels for participants with SVR by sex (mean with 95% CI); x-axis labels indicate the times during and after therapy, with sample numbers indicated in insets. Asterisks represent the first statistically significant differences, comparing baseline and time point during or after therapy (left panels) or comparing subgroups (middle and right panels). Panel A: IP-10; Panel B: Autotaxin; Panel C: Mac2BP; Panel D: IL-6. Abbreviations: ATX, autotaxin; IL-6, interleukin 6; IP-10, interferon-inducible protein 10; Mac2BP, Mac2-binding protein; PT, posttreatment.