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Interleukin 28 B Genotype Is a Potent Predictor of Response to Therapy with Pegylated Interferon plus Ribavirin in HIV/HCV Co-infected Patients
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Reported by jules Levin
CROI 2010 Feb 16-19 SF
Juan Pineda*1, A Caruz2, A Camacho3, K Neukam1, I Salas3, A Martinez3, J Macias1, J Mira1, J Palomares1, and A Rivero3
1Hosp Univ de Valme, Seville, Spain; 2Univ of Jaen, Spain; and 3Hosp Univ Reina Sofia, Cordoba, Spain
ABSTRACT
Background: Recent studies have shown that polymorphisms near the interleukin 28 B (IL28B) gen predict sustained virological response (SVR) to treatment with pegylated interferon (Peg-IFN) plus ribavirin (RBV) in hepatitis C virus (HCV)-monoinfected patients harboring genotype 1. However, HIV/HCV-co-infected patients have singularities regarding predictors of SVR, which could influence the predictive value of these polymorphisms. Moreover, there is no information on this topic in HCV genotypes other than 1. We aimed to assess if the polymorphism rs12979860, located 3 kb upstream of the IL28B gene, predicts SVR in HIV/HCV-coinfected patients with different genotypes.
Methods: A cohort of 146 consecutive HIV/HCV-co-infected patients started a first course of therapy against HCV in 2 hospitals in Spain. All subjects were prospectively followed up at least 24 weeks after the end of treatment. Patients received Peg-IFNα 2a or 2b at standard doses plus RBV 800 to 1200 mg/day. A whole blood sample was collected from all patients and cryopreserved at -70ºC. Genotyping was performed by TaqMan real time PCR.
Results: In this study, 71 (49%) patients harboured HCV genotype 1, 1 (1%) genotype 2, 51 (35%) HCV genotype 3 and 23 (16%) genotype 4. SVR was attained in 28% of patients with HCV genotype 1-4 and in 75% of those with genotype 2-3. 38 (62%) patients with rs12979860 CC achieved SVR versus 27 (32%) with TC or TT [OR (95%CI) = 3.5 (1.8 to 7.1), P <0.001].
Among patients with HCV genotype 1-4, 43% of those with CC vs 19% of those showing TC or TT reached SVR (P =0.022). The corresponding figures among genotype 2 to 3 carriers were 88% and 61% (P =0.051). A multivariate logistic regression analysis, including viral genotype, baseline HCV-RNA load, rs12979860 genotype, antiretroviral therapy, adherence to HCV-therapy and stage of liver fibrosis selected HCV genotype 2 or 3 [adjusted OR (95%CI) = 10.6 (3.8 to 29), P <0.001)], no advanced fibrosis [2.8 (1.1 to 7.1), P =0.031], HCV-RNA load ≤6x105 UI/mL [4.7 (1.8 to 12.1), P =0.001], adherence ≤80% [0.16 (0.03 to 0.91), P =0.038] and rs12979860 CC [3.9 (1.54 to 10], P =0.004] as independent predictors of SVR.
Conclusions: rs12979860 polymorphism upstream of IL28B gene has a marked impact on the probability of SVR to Peg-IFN plus RBV in HIV/HCV-coinfected patients. This effect is independent of viral genotype and other well-defined factors associated with therapy outcome. Screening for this polymorphism will be useful to properly select candidates for HCV therapy.
RESULTS
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