Hepatic histologic response (HR) to combination therapy among HCV/HIV-coinfected individuals: interferon induces HR independent of sustained virologic response (SVR).
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.
Wu
Lynne
L
Laboratory of Immunoregulation, NIAID, NIH, DHHS, Bethesda, Maryland, USA.
Kottilil
Shyam
S
Lempicki
Richard
R
Yang
Jun
J
McLaughlin
Mary
M
Hu
Zonghui
Z
Koratich
Chad
C
Reitano
Kristin N
KN
Rehm
Catherine A
CA
Masur
Henry
H
Wood
Brad
B
Kleiner
David E
DE
Polis
Michael A
MA
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*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b