Viral kinetics in hepatitis C or hepatitis C/human immunodeficiency virus-infected patients.
OBJECTIVE
Kinetic modeling of hepatitis C virus (HCV) response to interferon (IFN)-based therapy provides insights into factors associated with treatment outcomes. HCV/human immunodeficiency virus (HIV)-co-infected patients show lower response rates vs. HCV-monoinfected patients. Reasons for this remain unclear. This study evaluated kinetic parameters and treatment responses in co-infected vs monoinfected patients.


METHODS
Co-infected patients were randomized within a US multicenter trial (ACTG 5071) to receive pegylated-interferon (PEG-IFN) alfa-2a + ribavirin vs. IFN alfa-2a + ribavirin. Monoinfected controls were matched prospectively for treatment, genotype, age, sex, race, and histology. Quantitative HCV-RNA testing was performed at hours 0, 6, 12, 24, 48, and 72; days 7, 10, 14, 28, and 56; and weeks 12, 24, 48, and 72.


RESULTS
Twelve HCV/HIV-co-infected and 15 HCV-monoinfected patients underwent viral kinetic sampling. Among HIV-positive patients the mean CD4(+) count was 325 cells/mm(3). Seventy-five percent of patients were genotype 1. The HCV-RNA level was undetectable at 72 weeks in 25% and 40% of co-infected and monoinfected patients, respectively. Phase 1/2 declines, free virus clearance rate, and infected hepatocyte death rate were not affected by co-infection status but differed by treatment. Efficiency (epsilon) > or = 90% at 60 hours was associated with viral clearance ( P = .02). Modeling with pooled parameters suggests baseline viral load is a key factor in time to response in this cohort. Predicted clearance time increased by 28% in co-infected patients.


CONCLUSIONS
Co-infection status did not affect key kinetic parameters. Among kinetic parameters, efficiency was associated significantly with viral clearance. Co-infected patients may require longer treatment duration than monoinfected patients given their generally higher baseline viral loads.
Sherman
Kenneth E
KE
Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. Kenneth.sherman@uc.edu
Shire
Norah J
NJ
Rouster
Susan D
SD
Peters
Marion G
MG
James Koziel
Margaret
M
Chung
Raymond T
RT
Horn
Paul S
PS
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000821:virology*; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a