TY - JOUR
T1 - Intrahepatic viral kinetics during direct-acting antivirals for hepatitis c in human immunodeficiency virus coinfection
T2 - The AIDS Clinical Trials Group A5335S Substudy
AU - Balagopal, Ashwin
AU - Smeaton, Laura M.
AU - Quinn, Jeffrey
AU - Venuto, Charles S.
AU - Morse, Gene D.
AU - Vu, Vincent
AU - Alston-Smith, Beverly
AU - Cohen, Daniel E.
AU - Santana-Bagur, Jorge L.
AU - Anthony, Donald D.
AU - Sulkowski, Mark S.
AU - Wyles, David L.
AU - Talal, Andrew H.
N1 - Publisher Copyright:
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
KW - DAA therapy
KW - HIV/HCV coinfection
KW - Intrahepatic viral kinetics
KW - Single-cell laser capture microdissection
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U2 - 10.1093/infdis/jiaa126
DO - 10.1093/infdis/jiaa126
M3 - Article
C2 - 32201883
AN - SCOPUS:85088609385
SN - 0022-1899
VL - 222
SP - 601
EP - 610
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 4
ER -