Influence of HCV genotype 1 subtypes on the virus response to PEG interferon alpha‐2a plus ribavirin therapy

Abstract

New factors that influence the viral response in HCV non-genotype 2/3 patients must be identified in order to optimize anti-HCV treatment. This multicenter prospective study evaluates the influence of HCV variability and pharmacological parameters on the virological response of these patients to pegylated interferon α2a (peg-IFN-α2a: 180 µg/week) and ribavirin (RBV; 800-1,200 mg/day) for 48 weeks. HCV subtypes were identified by sequencing the NS5B region. Serum RBV and peg-IFN-α2a concentrations were measured at weeks 4 and 12. The 115 patients (67 men; median age = 49, range 31-76) included 64 who had never been treated and 27 co-infected with HIV. The mean baseline HCV RNA was 6.30 ± 0.06 log IU/ml and the HCV genotypes were: G1 (n = 93) with 1a (n = 37) and 1b (n = 50), G4 (n = 20) and G5 (n = 2). Most patients (79/108; 73%) had an early virological response. Independent predictors of an early virological response were interferon naive patients (OR= 2.98, 95% CI: 1.15-7.72) and RBV of >2,200 ng/ml at week 12 (OR = 3.41, 95% CI: 1.31-8.90). Forty of 104 patients (38%) had a sustained virological response. The only independent predictors of a sustained virological response were subtype 1b (OR = 6.82, 95% CI: 1.7-26.8), and HCV RNA <15 IU/ml at week 12 (OR = 25, 95% CI: 6.4-97.6). Thus a serum RBV concentration of >2,200 ng/ml was associated with an early virological response and patients infected with HCV subtype 1b had a better chance of a sustained virological response than did those infected with subtype 1a.

HCV genotype 1 subtypes (1a and 1b): similarities and differences in clinical features and therapeutic outcome

“…As to the sensitivity of HCV-1 subtypes to Peg-IFN and RIBA, there has been no consistency among studies in regard to a differential responsiveness of subtype 1a vs 1b on either on-and offtreatment parameters (6)(7)(8)(9)(10)(11)(12)(13). In our investigation, HCV clearance by week 4 and 12 of treatments, and at the end of treatment did not differ between patients carrying one or the other subtype ( Figure 1).…”

“…Results from the considered studies are summarized in the Supplementary (11)(12)(13), and two studies with significantly better rates in patients with subtype 1b (8,9). By pooling results from previous studies with those of the present investigation (Figure 2), the weighted SVR rates were not different between the two viral strains: OR = 0.98, CI 0.72-1.32.…”

“…Up to now, genotyping for HCV-1 subtypes will not impact on the day-to-day clinical management of chronic HCV infection, whereas conflicting reports exist on their influence on the outcome following conventional therapy with Peg-IFN and RIBA (6)(7)(8)(9)(10)(11)(12)(13). Recently, several HCV inhibitors appear to have selective activity against HCV 1 subtypes both in vitro and in vivo, with subtype 1a appearing more resistance-prone and less responsive to triple therapy than subtype 1b (25)(26)(27)(28)).…”

“…Major clinical trials evaluated treatment response among HCV-1a and 1b patients grouped together and, consequently, were unable to unveil a differential outcome of treatment between the two viral strains. Of available trials (7)(8)(9)(10)(11)(12)(13)(14), only few studies were sufficiently powered to detect an eventual difference, with some reporting a lower efficacy of Peg-IFN and RIBA in HCV-subtype 1a, and other studies unraveling an opposite finding. In addition, the impact of HCV-1 subtypes on the on-treatment response milestones, such as the rapid viral response at treatment week 4 (RVR), has not been extensively investigated.…”

Meta-analysis of the Efficacy and Safety of Grazoprevir and Elbasvir for the Treatment of Hepatitis C Virus Infection

“…[4][5][6] However, since the advent of various DAAs, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) have recommended a combination of two DAAs as drugs of choice in the treatment of HCV infection.…”