Safety and Efficacy of Pegylated Interferon Lambda, Ribavirin, and Daclatasvir in HCV and HIV-Coinfected Patients.

Abstract

To evaluate the efficacy and safety of pegylated interferon-lambda-1a (Lambda)/ribavirin (RBV)/daclatasvir (DCV) for treatment of patients coinfected with chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Treatment-naive patients were assigned to cohort A [HCV genotype (GT)-2 or -3] or cohort B [HCV GT-1(a or b) or -4]. All patients received Lambda/RBV/DCV for the first 12 weeks; cohort A received Lambda/RBV for an additional 12 weeks, followed by 24 weeks of follow-up, and cohort B received response-guided therapy. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post-treatment week 12 (SVR12). In cohort A (n = 104), 84.6% achieved SVR12 (95.0% in GT-2; 83.1% in GT-3). In cohort B (n = 196), 76.0% achieved SVR12 (71.7% in GT-1a; 86.0% in GT-1b; 70.7% in GT-4). Rates of discontinuation due to adverse events (AEs) (3.8% and 6.1%) and serious AEs (5.8% and 6.1%) were low in cohorts A and B, respectively. In addition, treatment with Lambda/RBV/DCV had little impact on CD4 counts. SVR12 rates with Lambda/RBV/DCV in an HCV/HIV-coinfected population ranged from 71.7% to 95.0%. Treatment was generally well tolerated, with a low proportion of patients discontinuing due to AEs. Clinical trial registration NCT01866930.

• Authors: Mark Nelson, Rafael Rubio, Adriano Lazzarin, Svetlana Romanova, Annie Luetkemeyer, Brian Conway, Jean-Michel Molina, Dong Xu, Subasree Srinivasan, Simon Portsmouth
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 37 Issue 3 Pg. 103-111 (03 2017) ISSN: 1557-7465 [Electronic] United States
• PMID: 28282271 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study)

Chemical References

• Carbamates
• Imidazoles
• Pyrrolidines
• interferon-lambda, human
• Ribavirin
• Interferons
• Valine
• daclatasvir

Topics

• Adult
• Aged
• CD4 Lymphocyte Count
• Carbamates
• Coinfection
• Drug Therapy, Combination
• Female
• Genotype
• HIV Infections (immunology, virology)
• Hepacivirus (genetics)
• Hepatitis C (drug therapy, virology)
• Humans
• Imidazoles (administration & dosage, adverse effects, therapeutic use)
• Interferons (administration & dosage, adverse effects, therapeutic use)
• Male
• Middle Aged
• Pyrrolidines
• Ribavirin (administration & dosage, adverse effects, therapeutic use)
• Treatment Outcome
• Valine (analogs & derivatives)
• Viral Load