title: Hepatic histologic response (HR) to combination therapy among HCV/HIV-coinfected individuals: interferon induces HR independent of sustained virologic response (SVR).
abstract: Most HIV/HCV-coinfected patients fail to achieve a sustained virologic response (SVR) to peginterferon-ribavirin therapy. We examined the hepatic histologic response (HR), defined as an improvement in hepatic inflammation scores of two points or more, to combination therapy among HIV/HCV-coinfected subjects. An open label prospective trial treated 32 HIV/HCV-coinfected patients with peginterferon alpha-2b and ribavirin for 48 weeks. Liver biopsies, scored by a single pathologist using the Histology Activity Index (HAI, range 0-18) and Ishak fibrosis scores (range 0-6), were performed before and after treatment. Gene expression profiles of PBMCs were performed using Affymetrix U133A gene chips. A total of 87% of SVR subjects and 88% of nonresponders (NR) had an HR, but no significant change in the liver fibrosis scores was observed (p > 0.05). For genotype 1 patients, a baseline fibrosis score </=2 was related to a higher likelihood of SVR than those with a score >2 (p = 0.012). Combination therapy for HCV among HIV-coinfected subjects resulted in a modest SVR rate. Persons with mild liver disease had a better SVR rate, suggesting early treatment may be beneficial. Combination therapy resulted in an HR for most of the patients, however, further follow-up of these patients will determine the durability of such an HR.
authors.affiliation: Laboratory of Immunoregulation, NIAID, NIH, DHHS, Bethesda, Maryland, USA.
authors.forename: Lynne
authors.initials: L
authors.lastname: Wu
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
authors.forename: Richard
authors.initials: R
authors.lastname: Lempicki
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Mary
authors.initials: M
authors.lastname: McLaughlin
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Hu
authors.forename: Chad
authors.initials: C
authors.lastname: Koratich
authors.forename: Kristin N
authors.initials: KN
authors.lastname: Reitano
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Rehm
authors.forename: Henry
authors.initials: H
authors.lastname: Masur
authors.forename: Brad
authors.initials: B
authors.lastname: Wood
authors.forename: David E
authors.initials: DE
authors.lastname: Kleiner
authors.forename: Michael A
authors.initials: MA
authors.lastname: Polis
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001706:Biopsy; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000473:pathology; D008297:Male; D010865:Pilot Projects; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b