title: Modulation of HCV replication after combination antiretroviral therapy in HCV/HIV co-infected patients.
abstract: The hepatitis C virus (HCV) is an important contributor to morbidity and mortality in patients co-infected with HIV. Co-infection results in increased HCV replication and more rapid rates of liver disease progression. The effect of HIV combination antiretroviral therapy (cART) on HCV replication has not been studied in depth. To address this issue, we enrolled a small cohort of HCV/HIV co-infected patients into a cART initiation trial and used dynamic modeling combined with evaluation of immune responses and microarray profiles to determine how effective treatment of HIV affects HCV. Treatment with cART resulted in increased HCV replication and increased alanine aminotransferase (ALT) in a subset of patients. Subjects with evidence of hepatic injury (increased ALT) were more likely to have HCV-specific immune responses directed against HCV epitopes. Over time, HCV viral loads declined. Reproducible and biologically important gene expression changes occurred in co-infected patients who underwent successful cART. The effective suppression of HIV by cART initiated a cascade of early and late events in treated patients. Early events involving down-regulation of interferon-stimulated genes may have led to transiently increased viral replication and hepatic injury. At later time points, HCV viral load declined to levels comparable to those seen in the setting of HCV monoinfection. These findings support early antiretroviral therapy in those with HCV/HIV co-infection.
authors.affiliation: University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA. kenneth.sherman@uc.edu.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Sherman
authors.affiliation: Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA. Institut National de la Santé et de la Recherche Médicale and Université Paris Diderot, Sorbonne Paris Cité, Unité Mixte de Recherche, Paris 75013, France.
authors.forename: Jeremie
authors.initials: J
authors.lastname: Guedj
authors.affiliation: University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Mohamed Tarek
authors.initials: MT
authors.lastname: Shata
authors.affiliation: University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Blackard
authors.affiliation: University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Susan D
authors.initials: SD
authors.lastname: Rouster
authors.affiliation: Escuela Técnica Superior de Ingeniería, Universidad Pontificia Comillas, 28015 Madrid, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Castro
authors.affiliation: University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Feinberg
authors.affiliation: Virginia Commonwealth University, Richmond, VA 23284, USA.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Sterling
authors.affiliation: Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA 22042, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Goodman
authors.affiliation: Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Aronow
authors.affiliation: Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Perelson
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active; D060085:Coinfection / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology; D019562:Viral Load / Q000276:immunology; D014779:Virus Replication; D055815:Young Adult
chemical_list: D012367:RNA, Viral; D000410:Alanine Transaminase
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