Shortened Therapy of Eight Weeks With Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir Is Highly Effective in People With Recent HCV Genotype 1 Infection

M. Martinello; S. Bhagani; E. Gane; C. Orkin; G. Cooke; G. J. Dore; K. Petoumenos; T. L. Applegate; E. Tu; P. Marks; N. Pagani; J. Grebely; M. Nelson; G. V. Matthews

Disclosures

J Viral Hepat. 2018;25(10):1180-1188. 

In This Article

Abstract and Introduction

Abstract

Paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 12 weeks are approved for treatment of chronic HCV genotype 1 infection. This study assessed the efficacy of shortened duration paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 8 weeks among people with recent HCV infection. In this open-label single-arm trial conducted in Australia, England and New Zealand, adults with recent HCV (duration of infection <12 months) received paritaprevir/ritonavir/ombitasvir and dasabuvir (with weight-based ribavirin for genotypes 1a and 1, no subtype) for 8 weeks. The primary endpoint was sustained virological response at 12 weeks post-treatment (SVR12) in the intention-to-treat (ITT) population. Thirty people (median age 38 years, male 93%) commenced treatment (with ribavirin, 97%), of whom 77% (n = 23) were HIV-positive, 93% (n = 28) had genotype 1a infection and 53% (n = 16) had ever injected drugs. Median maximum ALT in the preceding 12 months was 433 IU/L (IQR 321, 1012). Acute clinical hepatitis with ALT > 10 x ULN was documented in 83% (n = 25); one participant (3%) had jaundice. At baseline, median estimated duration of infection was 30 weeks (range 11, 51), and median HCV RNA was 5.7 log10 IU/mL (range 2.7, 7.3). SVR12 was achieved in 97% (29/30; early discontinuation at week 2, n = 1; per protocol 100%, 29/29). No relapse or reinfection was observed. In conclusion, paritaprevir/ritonavir/ombitasvir and dasabuvir (with ribavirin) for eight weeks were highly effective among HIV-positive and HIV-negative individuals with recent HCV infection. These data support the use of this shortened duration direct-acting antiviral regimen in this population.

Introduction

Globally, an estimated 1.75 million new HCV infections occurred in 2015, with at-risk populations including people who inject drugs (PWID) and HIV-positive gay and bisexual men (GBM).[1–3] With interferon-free direct-acting antiviral (DAA) therapy established as the standard of care for chronic HCV infection, the optimal management of acute (within 6 months) and recent (within 12 months) HCV is yet to be defined. Very high efficacy (sustained virological response, SVR) and safety are observed with dual- or triple-class DAA regimens for eight to 12 weeks in chronic HCV infection, particularly among treatment-naïve individuals without cirrhosis.[4–7]

Current recommendations for the treatment of acute HCV infection are based on expert opinion.[8,9] The paradigm of enhanced efficacy with shortened duration interferon-based therapy in recent, as compared with chronic HCV infection, underpins current research questions.[10] Clinical trials evaluating shortened duration DAA regimens in acute and recent HCV infection are underway, with early data providing encouraging results.[11,12] Screening strategies in at-risk populations recommend at least annual HCV testing.[8,9,13,14] If these recommendations are adhered to, HCV primary infection and reinfection should be diagnosed within the first year of acquisition. As individuals diagnosed with recent HCV infection are interested in considering treatment,[15] this initial assessment represents an ideal opportunity for intervention, with benefits at both an individual level and the population level, largely related to averting onward transmission.[16–18] Cost-effectiveness analysis supports immediate treatment of acute HCV with short-duration DAA therapy as compared with treatment deferral until chronic infection, given cost savings associated with shorter treatment duration and reduced transmission.[18]

Paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 12 weeks are approved and recommended as first-line treatment for chronic HCV genotype 1 infection.[8,9] The aim of this study was to assess the efficacy and safety of shortened duration paritaprevir/ritonavir/ombitasvir and dasabuvir with or without ribavirin for 8 weeks in individuals with recent HCV infection (estimated duration of infection <12 months).

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