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.

• Authors: Donald D Anthony, Mark S Sulkowski, Laura M Smeaton, Sofi Damjanovska, Carey L Shive, Corinne M Kowal, Daniel E Cohen, Debika Bhattacharya, Beverly L Alston-Smith, Ashwin Balagopal, David L Wyles
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 222 Issue 8 Pg. 1334-1344 (09 14 2020) ISSN: 1537-6613 [Electronic] United States
• PMID: 32406487 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Published by Oxford University Press for the Infectious Diseases Society of America 2020.

Chemical References

• Anilides
• Anti-HIV Agents
• Antiviral Agents
• Biomarkers
• Carbamates
• Cyclopropanes
• Immunologic Factors
• Lactams, Macrocyclic
• Sulfonamides
• ombitasvir
• Ribavirin
• Uracil
• Proline
• 2-Naphthylamine
• dasabuvir
• Valine
• Ritonavir
• paritaprevir

Topics

• 2-Naphthylamine
• Adult
• Anilides (therapeutic use)
• Anti-HIV Agents (therapeutic use)
• Antiviral Agents (therapeutic use)
• Biomarkers (blood)
• Carbamates (therapeutic use)
• Coinfection (drug therapy, immunology)
• Cyclopropanes (therapeutic use)
• Drug Therapy, Combination
• Female
• Genotype
• HIV Infections (drug therapy, immunology)
• HIV-1 (drug effects)
• Hepacivirus (drug effects)
• Hepatitis C, Chronic (drug therapy, immunology)
• Humans
• Immunologic Factors (blood)
• Lactams, Macrocyclic (therapeutic use)
• Liver Cirrhosis (drug therapy, immunology)
• Male
• Middle Aged
• Proline (analogs & derivatives, therapeutic use)
• Ribavirin (therapeutic use)
• Ritonavir (therapeutic use)
• Sulfonamides (therapeutic use)
• Sustained Virologic Response
• Uracil (analogs & derivatives, therapeutic use)
• Valine