Intrahepatic viral kinetics during direct-acting antivirals for hepatitis c in human immunodeficiency virus coinfection: The AIDS Clinical Trials Group A5335S Substudy

Ashwin Balagopal, Laura M. Smeaton, Jeffrey Quinn, Charles S. Venuto, Gene D. Morse, Vincent Vu, Beverly Alston-Smith, Daniel E. Cohen, Jorge L. Santana-Bagur, Donald D. Anthony, Mark S. Sulkowski, David L. Wyles, Andrew H. Talal

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)601-610
Number of pages10
JournalJournal of Infectious Diseases
Volume222
Issue number4
DOIs
StatePublished - Aug 1 2020

Keywords

  • DAA therapy
  • HIV/HCV coinfection
  • Intrahepatic viral kinetics
  • Single-cell laser capture microdissection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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