Insulin resistance predicts re-treatment failure in an efficacy study of peginterferon-α-2a and ribavirin in HIV/HCV co-infected patients

Journal of Hepatology
Volume 54, Issue 1, Pages 41-47

Marie-Louise C. Vachon 1† , Stephanie H. Factor 2† , Andrea D. Branch 1† , Maria-Isabel Fiel 3† , Maribel Rodriguez-Torres 4† , Norbert Bräu 56† , Richard K. Sterling 7† , Jihad Slim 8† , Andrew H. Talal 9† , Douglas T. Dieterich 1† , Mark S. Sulkowski 10†

Received 19 February 2010; received in revised form 11 June 2010; accepted 16 June 2010.

Background & Aims
Few studies evaluated the efficacy of HCV re-treatment and the predictors of response in HIV/HCV co-infected patients. The role of insulin resistance as a predictor of response in this population is unknown. The aim of this study is to evaluate the safety and efficacy of pegylated interferon-α-2a and ribavirin in re-treatment of HIV/HCV co-infected patients, predictors of sustained virological response, including insulin resistance, and the relationship between insulin resistance and liver histology.

Methods
This prospective, multi-centered study included HIV/HCV co-infected patients with prior interferon-based treatment failure. Patients received pegylated interferon-α-2a and ribavirin for 48weeks. Serum HCV RNA was measured 24weeks post treatment to assess sustained virological response. Insulin resistance was defined as HOMA-IR>2. Correlations between baseline insulin resistance and steatosis, and/or cirrhosis were determined.

Results
Sustained virological response was achieved in 14/96 (15%) patients. 35% of patients with HOMA-IR<2 (6/17) achieved sustained virological response vs 14% (5/36) of those with HOMA-IR between 2–4, and 7% (3/41) of those with HOMA-IR>4 (p=0.01). In multivariable analysis, insulin resistance and log10 HCV RNA were negatively associated with sustained virological response [AOR 0.17; 95% CI 0.05–0.64, p=0.009, and AOR 0.36; 95% CI 0.14–0.93, p=0.04, respectively]. Steatosis and cirrhosis correlated with insulin resistance (p=0.02 and 0.03, respectively) but neither independently predicted sustained virological response. Discontinuations due to severe adverse events occurred in 8% of cases, and 2 patients died of unrelated causes.

Conclusions
In HIV/HCV co-infected patients undergoing re-treatment, sustained virological response rate is low; those patients without insulin resistance are significantly more likely to achieve sustained virological response.

Keywords: Insulin resistance, Hepatitis C virus, Chronic, HIV, Re-treatment, Antiviral therapy, Pegylated interferon alfa-2a, Ribavirin

1 Division of Liver Diseases, Mount Sinai School of Medicine, NY, USA
2 Division of Infectious Diseases, Mount Sinai School of Medicine, NY, USA
3 Department of Pathology, Mount Sinai School of Medicine, NY, USA
4 Fundacion de Investigacion de Diego, San Juan, PR, USA
5 Divisions of Infectious Diseases and Liver Diseases, Mount Sinai School of Medicine, NY, USA
6 Veterans Affairs Medical Center, Bronx, NY, USA
7 Division of Liver Diseases, Virginia Commonwealth University Health Systems, Richmond, VA, USA
8 Division of Infectious Diseases, St-Michael’s Medical Center, NY, USA
9 Division of Gastroenterology and Hepatology and Center for the Study of Hepatitis C, Weill Cornell Medical College, NY, USA
10 Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MA, USA

Corresponding author. Address: Mount Sinai School of Medicine, One, Gustave L. Levy Place, Box 1123, NY 10029, USA. Tel.: +1 212 659 8877; fax: +1 212 659 8377.

† On behalf of Hepatitis Resource Network (HRN)-004.

PII: S0168-8278(10)00715-4
doi:10.1016/j.jhep.2010.06.025
© 2010 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.

Source