Intrahepatic Viral Kinetics During Direct-Acting Antivirals for Hepatitis C in Human Immunodeficiency Virus Coinfection : The AIDS Clinical Trials Group A5335S Substudy
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissionsoup.com..
BACKGROUND: Direct-acting antivirals (DAAs) targeting hepatitis C virus (HCV) have revolutionized outcomes in human immunodeficiency virus (HIV) coinfection.
METHODS: We examined early events in liver and plasma through A5335S, a substudy of trial A5329 (paritaprevir/ritonavir, ombitasvir, dasabuvir, with ribavirin) that enrolled chronic genotype 1a HCV-infected persons coinfected with suppressed HIV: 5 of 6 treatment-naive enrollees completed A5335S.
RESULTS: Mean baseline plasma HCV ribonucleic acid (RNA) = 6.7 log10 IU/mL and changed by -4.1 log10 IU/mL by Day 7. In liver, laser capture microdissection was used to quantify HCV. At liver biopsy 1, mean %HCV-infected cells = 25.2% (95% confidence interval [CI], 7.4%-42.9%), correlating with plasma HCV RNA (Spearman rank correlation r = 0.9); at biopsy 2 (Day 7 in 4 of 5 participants), mean %HCV-infected cells = 1.0% (95% CI, 0.2%-1.7%) (P < .05 for change), and DAAs were detectable in liver. Plasma C-X-C motif chemokine 10 (CXCL10) concentrations changed by mean = -160 pg/mL per day at 24 hours, but no further after Day 4.
CONCLUSIONS: We conclude that HCV infection is rapidly cleared from liver with DAA leaving <2% HCV-infected hepatocytes at Day 7. We extrapolate that HCV eradication could occur in these participants by 63 days, although immune activation might persist. Single-cell longitudinal estimates of HCV clearance from liver have never been reported previously and could be applied to estimating the minimum treatment duration required for HCV infection.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:222 |
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| Enthalten in: |
The Journal of infectious diseases - 222(2020), 4 vom: 23. Juli, Seite 601-610 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Balagopal, Ashwin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.02.2021 Date Revised 10.08.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/infdis/jiaa126 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM307881806 |
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| 100 | 1 | |a Balagopal, Ashwin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Intrahepatic Viral Kinetics During Direct-Acting Antivirals for Hepatitis C in Human Immunodeficiency Virus Coinfection |b The AIDS Clinical Trials Group A5335S Substudy |
| 264 | 1 | |c 2020 | |
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| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 16.02.2021 | ||
| 500 | |a Date Revised 10.08.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissionsoup.com. | ||
| 520 | |a BACKGROUND: Direct-acting antivirals (DAAs) targeting hepatitis C virus (HCV) have revolutionized outcomes in human immunodeficiency virus (HIV) coinfection | ||
| 520 | |a METHODS: We examined early events in liver and plasma through A5335S, a substudy of trial A5329 (paritaprevir/ritonavir, ombitasvir, dasabuvir, with ribavirin) that enrolled chronic genotype 1a HCV-infected persons coinfected with suppressed HIV: 5 of 6 treatment-naive enrollees completed A5335S | ||
| 520 | |a RESULTS: Mean baseline plasma HCV ribonucleic acid (RNA) = 6.7 log10 IU/mL and changed by -4.1 log10 IU/mL by Day 7. In liver, laser capture microdissection was used to quantify HCV. At liver biopsy 1, mean %HCV-infected cells = 25.2% (95% confidence interval [CI], 7.4%-42.9%), correlating with plasma HCV RNA (Spearman rank correlation r = 0.9); at biopsy 2 (Day 7 in 4 of 5 participants), mean %HCV-infected cells = 1.0% (95% CI, 0.2%-1.7%) (P < .05 for change), and DAAs were detectable in liver. Plasma C-X-C motif chemokine 10 (CXCL10) concentrations changed by mean = -160 pg/mL per day at 24 hours, but no further after Day 4 | ||
| 520 | |a CONCLUSIONS: We conclude that HCV infection is rapidly cleared from liver with DAA leaving <2% HCV-infected hepatocytes at Day 7. We extrapolate that HCV eradication could occur in these participants by 63 days, although immune activation might persist. Single-cell longitudinal estimates of HCV clearance from liver have never been reported previously and could be applied to estimating the minimum treatment duration required for HCV infection | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a DAA therapy | |
| 650 | 4 | |a HIV/HCV coinfection | |
| 650 | 4 | |a intrahepatic viral kinetics | |
| 650 | 4 | |a single-cell laser capture microdissection | |
| 650 | 7 | |a Anilides |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Carbamates |2 NLM | |
| 650 | 7 | |a Cyclopropanes |2 NLM | |
| 650 | 7 | |a Lactams, Macrocyclic |2 NLM | |
| 650 | 7 | |a Sulfonamides |2 NLM | |
| 650 | 7 | |a ombitasvir |2 NLM | |
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| 650 | 7 | |a Ribavirin |2 NLM | |
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| 650 | 7 | |a paritaprevir |2 NLM | |
| 650 | 7 | |a OU2YM37K86 |2 NLM | |
| 700 | 1 | |a Smeaton, Laura M |e verfasserin |4 aut | |
| 700 | 1 | |a Quinn, Jeffrey |e verfasserin |4 aut | |
| 700 | 1 | |a Venuto, Charles S |e verfasserin |4 aut | |
| 700 | 1 | |a Morse, Gene D |e verfasserin |4 aut | |
| 700 | 1 | |a Vu, Vincent |e verfasserin |4 aut | |
| 700 | 1 | |a Alston-Smith, Beverly |e verfasserin |4 aut | |
| 700 | 1 | |a Cohen, Daniel E |e verfasserin |4 aut | |
| 700 | 1 | |a Santana-Bagur, Jorge L |e verfasserin |4 aut | |
| 700 | 1 | |a Anthony, Donald D |e verfasserin |4 aut | |
| 700 | 1 | |a Sulkowski, Mark S |e verfasserin |4 aut | |
| 700 | 1 | |a Wyles, David L |e verfasserin |4 aut | |
| 700 | 1 | |a Talal, Andrew H |e verfasserin |4 aut | |
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