Role of Weight-Based Ribavirin Dosing and Extended Duration of Therapy in Chronic Hepatitis C in HIV-Infected Patients: The PRESCO Trial

Abstract

The response to pegylated interferon (pegIFN) plus ribavirin (RBV) as treatment of chronic hepatitis C virus (HCV) infection is lower in HIV-coinfected than in HCV-monoinfected patients and could be due to suboptimal RBV dosing and/or insufficient duration of therapy in prior trials. In a prospective, multicenter, open, comparative trial, HCV/HIV-coinfected patients received pegIFN plus weight-based RBV for 48 or 72 weeks (HCV genotypes 1 and 4) and 24 or 48 weeks (HCV genotypes 2 and 3). Use of didanosine was not allowed. Out of 389 patients included in the trial, 61% were infected by HCV-1/4 and 67% had serum HCV-RNA >500,000 IU/ml. Sustained virological response (SVR) was achieved by 49.6%, significantly higher in HCV-2/3 than HCV-1/4 (72.4% vs. 35%; p < 0.0001). A high drop-out rate in the longer treatment arms precluded obtaining definitive conclusions about the efficacy of prolonging therapy. Premature treatment discontinuations due to serious adverse events occurred in 8.2%. Infection with HCV-2/3, lower baseline HCV-RNA, and negative HCV-RNA at week 12 were all independent predictors of SVR in the multivariate analysis. The use of RBV 1000-1200 mg/day plus pegIFN is relatively safe and provides SVR in nearly half of coinfected patients, twice as high in HCV-2/3 than HCV-1/4.

Influence of a Single Nucleotide Polymorphism at the Main Ribavirin Transporter Gene on the Rapid Virological Response to Pegylated Interferon–Ribavirin Therapy in Patients with Chronic Hepatitis C Virus Infection

“…Treatment for chronic HCV infection is associated with frequent adverse effects, is expensive, and on average only provides cure to 30%-40% of HIV-HCV-coinfected patients [3,4,6]. Therefore, identification of the subset of patients with the greatest chance of treatment response is important.…”

“…This figure, however, is lower (25%-50%) in the subset of patients coinfected with human immunodeficiency virus (HIV) [3][4][5][6]. Approximately one-fourth of HIVinfected individuals worldwide are coinfected with HCV [5]; liver disease progresses faster to cirrhosis in this population [7,8].…”

Recent Hepatitis C Virus Infections in HIV-Infected Patients in Taiwan: Incidence and Risk Factors

“…In HCV-monoinfected patients treated with pegylated IFN plus ribavirin, the overall sustained virologic response (SVR) is 41% to 64% (12,18,25,34). In contrast, in HIV/HCV-coinfected patients treated with pegylated IFN plus ribavirin, the overall SVR in those infected with HCV genotype 1 is only 17% to 50% (4,30,31,39). While more studies are needed to identify the optimal treatments for HIV-infected patients with acute HCV infection (33), the treatment responses seen with acute HCV infection in HIVinfected populations are promising, with an overall SVR of 46% to 95%, even in patients with genotype 1 or 4 infections (1,43).…”

Perspectivas futuras en el tratamiento de la hepatitis crónica C

“…Firstly, the efficacy of treatment highly depends on factors related not only to patients, but also to virus or treatment. The presence of co-infection with HIV, frequent in the prison setting, conditions lower rates of SVR, as confirmed by many studies 11,12 . Similarly, the use of Peg-IFN based therapy is contraindicated for certain clinical conditions (major depressive disorder, decompensated cirrhosis, etc.)…”