Influence of IL28B polymorphisms on response to a lower-than-standard dose peg-IFN-α 2a for genotype 3 chronic hepatitis C in HIV-coinfected patients

Abstract

Background: Data on which to base definitive recommendations on the doses and duration of therapy for genotype 3 HCV/HIV-coinfected patients are scarce. We evaluated the efficacy of a lower peginterferon-α 2a dose and a shorter duration of therapy than the current standard of care in genotype 3 HCV/HIV-coinfected patients.

Methods and findings: Pilot, open-label, single arm clinical trial which involved 58 Caucasian HCV/HIV-coinfected patients who received weekly 135 µg peginterferon-α 2a plus ribavirin 400 mg twice daily during 20 weeks after attaining undetectable viremia. The relationships between baseline patient-related variables, including IL28B genotype, plasma HCV-RNA, ribavirin dose/kg, peginterferon-α 2a and ribavirin levels with virological responses were analyzed. Only 4 patients showed lack of response and 5 patients dropped out due to adverse events related to the study medication. Overall, sustained virologic response (SVR) rates were 58.3% by intention-to-treat and 71.4% by per protocol analysis, respectively. Among patients with rapid virologic response (RVR), SVR and relapses rates were 92.6% and 7.4%, respectively. No relationships were observed between viral responses and ribavirin dose/kg, peginterferon-α 2a concentrations, ribavirin levels or rs129679860 genotype.

Conclusions: Weekly 135 µg pegIFN-α 2a could be as effective as the standard 180 µg dose, with a very low incidence of severe adverse events. A 24-week treatment duration appears to be appropriate in patients achieving RVR, but extending treatment up to just 20 weeks beyond negativization of viremia is associated with a high relapse rate in those patients not achieving RVR. There was no influence of IL28B genotype on the virological responses.

Trial registration: ClinicalTrials.gov NCT00553930.

Conflict of interest statement

Competing Interests: LL-C, PV, F. Lozano, and AR have received honoraria for speaking at symposia organized on behalf of Abbott laboratories (Spain), Bristol-Myers Squibb, GlaxoSmithkline, Gilead Sciences, Janssen-Cilag España, Merck Sharp & Dohme España, Roche Pharma SA; and have also received unrestricted funds for research from Abbott Laboratories (Spain), Bristol-Myers Squibb, Boehringer Ingelheim España S.A, GlaxoSmithkline, and Roche Pharma SA. Other authors: none to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1. Study flow diagram.

RVR: rapid virological response. EVR: early virological response. ETR: end of treatment response. SVR: sustained virological response. AEs: adverse events.

Figure 2. Peginterferon-α-2a (A) and ribavirin (B) trough plasma levels at different time points. Median (range).

Figure 3. Percentage of virological responses and relapses as function of rs129679860 genotype (CC vs. CT/TT).

RVR: rapid virological response; EVR: early virological response; ETR: end of treatment response; SVR: sustained virological response.