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.
2-Naphthylamine
Adult
Anilides
/ therapeutic use
Anti-HIV Agents
/ therapeutic use
Antiviral Agents
/ therapeutic use
Biomarkers
/ blood
Carbamates
/ therapeutic use
Coinfection
/ drug therapy
Cyclopropanes
/ therapeutic use
Drug Therapy, Combination
Female
Genotype
HIV Infections
/ drug therapy
HIV-1
/ drug effects
Hepacivirus
/ drug effects
Hepatitis C, Chronic
/ drug therapy
Humans
Immunologic Factors
/ blood
Lactams, Macrocyclic
/ therapeutic use
Liver Cirrhosis
/ drug therapy
Male
Middle Aged
Proline
/ analogs & derivatives
Ribavirin
/ therapeutic use
Ritonavir
/ therapeutic use
Sulfonamides
/ therapeutic use
Sustained Virologic Response
Uracil
/ analogs & derivatives
Valine
DAA therapy
hepatitis C
human
immunity
inflammation
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
14 09 2020
14 09 2020
Historique:
received:
21
01
2020
accepted:
06
05
2020
pubmed:
15
5
2020
medline:
6
3
2021
entrez:
15
5
2020
Statut:
ppublish
Résumé
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. 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. 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. 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. NCT02194998.
Sections du résumé
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.
Identifiants
pubmed: 32406487
pii: 5836999
doi: 10.1093/infdis/jiaa254
pmc: PMC7749191
doi:
Substances chimiques
Anilides
0
Anti-HIV Agents
0
Antiviral Agents
0
Biomarkers
0
Carbamates
0
Cyclopropanes
0
Immunologic Factors
0
Lactams, Macrocyclic
0
Sulfonamides
0
ombitasvir
2302768XJ8
Ribavirin
49717AWG6K
Uracil
56HH86ZVCT
Proline
9DLQ4CIU6V
2-Naphthylamine
CKR7XL41N4
dasabuvir
DE54EQW8T1
Valine
HG18B9YRS7
Ritonavir
O3J8G9O825
paritaprevir
OU2YM37K86
Banques de données
ClinicalTrials.gov
['NCT02194998']
Types de publication
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.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1334-1344Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI106701
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068634
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI116868
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI068636
Pays : United States
Organisme : BLRD VA
ID : I01 BX001894
Pays : United States
Organisme : NIDA NIH HHS
ID : K24 DA034621
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI069424
Pays : United States
Organisme : CSRD VA
ID : IK2 CX001471
Pays : United States
Informations de copyright
Published by Oxford University Press for the Infectious Diseases Society of America 2020.
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