Intrahepatic Viral Kinetics During Direct-Acting Antivirals for Hepatitis C in Human Immunodeficiency Virus Coinfection: The AIDS Clinical Trials Group A5335S Substudy.
J Infect Dis
; 222(4): 601-610, 2020 07 23.
Article
en En
| MEDLINE
| ID: mdl-32201883
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) =â 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 cellsâ =â 25.2% (95% confidence interval [CI], 7.4%-42.9%), correlating with plasma HCV RNA (Spearman rank correlation râ =â 0.9); at biopsy 2 (Day 7 in 4 of 5 participants), mean %HCV-infected cellsâ =â 1.0% (95% CI, 0.2%-1.7%) (Pâ <â .05 for change), and DAAs were detectable in liver. Plasma C-X-C motif chemokine 10 (CXCL10) concentrations changed by meanâ =â -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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antivirales
/
Síndrome de Inmunodeficiencia Adquirida
/
Hepatitis C Crónica
/
Coinfección
Tipo de estudio:
Clinical_trials
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
America do norte
Idioma:
En
Revista:
J Infect Dis
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos