Abstract
ObjectiveTo establish the role of liver fibrosis as a predictive tool of response to pegylated interferon alpha (Peg-IFN) and ribavirin (RBV) treatment in human immunodeficiency (HIV)/hepatitis C virus (HCV) coinfected patients, in addition to recognized predictive factors (HCV load, HCV genotype, IL-28B polymorphism).Patients and MethodsA sample of 267 HIV/HCV coinfected patients was treated with Peg-IFN and RBV. Predictive factors of rapid (RVR) and sustained (SVR) virological response were analyzed. Independent variables were age, sex, IL28B, −238 TNF-α and −592 IL-10 polymorphisms, HCV genotype, HCV-RNA levels, significant fibrosis or cirrhosis and CD4+ T cell count.ResultsPatients infected by HCV genotype 1 (n = 187) showed RVR and SVR in 12% and 39% of cases, respectively. The parameters associated with RVR were IL28B genotype CC and plasma HCV-RNA levels <600000 IU/ml. Advanced liver fibrosis was negatively associated with SVR in patients without RVR. A SVR was obtained in 42% of subjects with HCV genotype 4, and the independent factors associated with SVR were IL28B genotype CC and an HCV-RNA <600000 IU/ml. A SVR was obtained in 66% of patients with HCV genotypes 2/3; in this case, the independent parameter associated with SVR was the absence of significant liver fibrosis. TNF-α and IL-10 polymorphisms were not associated with SVR, although a significantly higher percentage of −238 TNF-α genotype GG was detected in patients with significant liver fibrosis.ConclusionsIn HIV/HCV coinfected patients with HCV genotypes 1 or 4, RVR, mainly influenced by genotype IL28B and HCV-RNA levels, reliably predicted SVR after 4 weeks of therapy with Peg-IFN plus RBV. In patients infected by HCV genotype 3, an elevated relapse rate compromised the influence of RVR on SVR. Relapses were related to the presence of advanced liver fibrosis. Liver cirrhosis was associated with a −238 TNF-α polymorphism in these patients.
Highlights
Until recently, hepatitis C virus (HCV) infection has been treated with a combination of pegylated interferon alpha (PegIFN) and ribavirin (RBV)
A sustained virologic response (SVR) was obtained in 42% of subjects with HCV genotype 4, and the independent factors associated with SVR were interleukin 28B (IL28B) genotype CC and an HCV-RNA,600000 IU/ml
A SVR was obtained in 66% of patients with HCV genotypes 2/3; in this case, the independent parameter associated with SVR was the absence of significant liver fibrosis
Summary
Hepatitis C virus (HCV) infection has been treated with a combination of pegylated interferon alpha (PegIFN) and ribavirin (RBV). The HCV protease inhibitors telaprevir and boceprevir, in combination with Peg-IFN plus RBV, as well as sofosbuvir and simeprevir, have been introduced as treatment for HCV infections [2,3]. The series of HIV-infected patients coinfected by HCV and treated with these direct-acting antivirals has been limited, studies have demonstrated a higher percentage of responses than those obtained with the combination of Peg-IFN plus RBV alone [4,5,6]. Sofosbuvir and IFN-free regimens have been proven to be efficacious in HIV/HCV coinfection (PHOTON-1 trial), with minimal side effects and drug interactions [9]. The study of parameters associated with elevated responses to dual therapy (Peg-IFN and RBV combination), which could render the use of telaprevir, boceprevir, sofosbuvir or simeprevir unnecessary, is a key feature of HIV clinical practice
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call