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

摘要

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-alpha-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-alpha-2a and ribavirin for 48 weeks. Serum HCV RNA was measured 24 weeks 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 log 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.