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

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.

Abbreviations: HIV, human immunodeficiency virus, HCV, hepatitis C virus, HRN, hepatitis Resource Network, HCV RNA, hepatitis C virus ribonucleic acid, HOMA-IR, homeostasis model of assessment of insulin resistance, AOR, adjusted odds ratio, CI, confidence interval, HCC, hepatocellular carcinoma, SVR, sustained virological response, PegIFN, pegylated interferon, RBV, ribavirin, IR, insulin resistance, IFN, interferon, HIV RNA, human immunodeficiency virus ribonucleic acid, ART, antiretroviral therapy, ULN, upper limit of normal, Hb, hemoglobin, HbA1c, hemoglobin A1c, TSH, thyroid-stimulating hormone, pEVR, partial early virological response, cEVR, complete early virological response, EOT, end of treatment, IRB, institutional review board, HAI, histology activity index, BMI, body mass index, IQR, interquartile range, OR, odds ratio, SAE, severe adverse event, RVR, rapid virological response, ACTG, AIDS Clinical Trials Group, SOCS3, suppressor of cytokine signaling 3, IRS-1, insulin receptor substrate 1, STAT-1, signal transducers and activators of transcription 1

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