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Insulin Resistance Is a Major Predictor of Sustained Virological Response to Peginterferon and Ribavirin in HIV/HCV Co-infected Patients Undergoing HCV Retreatment
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Reported by Jules Levin
CROI 2010 Feb 16-19 SF
Marie-Louise Vachon*1, S Factor1, A Branch1, M I Fiel1, M Sulkowski2, D Dieterich1, and HRN-004 Study Group
1Mt Sinai Sch of Med, New York, NY, US and 2Johns Hopkins Hosp, Baltimore, MD, US
ABSTRACT
Background: Insulin resistance (IR) is a negative predictive factor of sustained virological response (SVR) in treatment of hepatitis C virus (HCV) mono-infected patients. Its predictive value in treatment-naïve HIV/HCV co-infected patients is uncertain and its predictive value in co-infected patients undergoing retreatment has not been investigated.
Methods: HRN-004 was a multi-center, open-label, phase IIIb study investigating peginterferon α-2a and weight-based ribavirin for the treatment of HCV in HIV co-infected patients who had previously failed to achieve SVR. We performed a matched nested case-control study to evaluate the role of IR [homeostasis model of assessment of insulin resistance (HOMA-IR) >2] in predicting SVR. Cases were subjects who achieved SVR and controls were those who did not. Subjects were matched by genotype and HCV RNA within 100,000 IU/ml and a multivariate conditional logistic regression analysis was done (with variables with P≤0.20 in the univariate analysis).
Results: Eighty-one patients were included. The median age was 49 (IQR, 44 to 53); 85% male; 30% Caucasian, 25% African American and 43% Latino; 89% genotype 1; median HCV RNA 6.2X105 (IQR, 4.2X105 to 4.2X106 IU/mL); median BMI 25.8 (IQR 23.8 to 30.0); median CD4+ cell count 564 (IQR, 364 to 755); 79% on antiretroviral therapy (ART), 45% PI-based and 42% NNRTI-based; 56% with at least mild steatosis at baseline liver biopsy and 30% with cirrhosis. Sixty-eight (84%) subjects had IR, defined as a HOMA-IR >2. Fourteen (17%) patients achieved SVR. In the matched univariate analysis, the only predictor of SVR was the absence of IR (HOMA-IR ≤2) (OR = 7.8, 95%CI 1.8 to 33.9, P <0.006). In multivariate analysis adjusted for age, gender, CD4+ cell count, HCV risk factor, steatosis and NNRTI-based ART, NNRTI-based ART showed significant association with SVR (AOR = 6.73, 95%CI 1.00 to 45.12, P =0.05) and absence of IR remained the strongest predictor of SVR (AOR = 10.23, 95%CI 1.91 to 54.73, P=0.007). Forty-five percent of patients with HOMA-IR <2 achieved SVR compared to 15% with HOMA-IR between 2 and 4 (P =0.05) and 9% of those with HOMA-IR >4 (P =0.007).
Conclusions: Our data suggest that absence of IR (HOMA-IR ≤2) is a strong predictor of SVR in HCV/HIV co-infected patients undergoing retreatment with peginterferon-α2a and ribavirin. Baseline HOMA-IR should be calculated in all patients with HIV considering retreatment of HCV to best inform the patient about the chances of success in the decision to retreat.
RESULTS
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