Direct‐acting antiviral drugs for the treatment of chronic hepatitis C virus infection: Interferon free is now

Abstract

Chronic hepatitis C (CHC) is a global, serious, and life-threatening disease. Virologic response at 12 weeks post-treatment (SVR12) signifies a durable virologic response and is currently the primary efficacy endpoint used in registrational trials. This change led to more rapid clinical development and earlier approvals of highly effective and well-tolerated therapies, facilitating access to those in need. Hepatitis C virus (HCV) infection is a therapeutic area where mathematical modeling has proven helpful in understanding the drug mechanism and characterizing viral kinetics to inform therapy decisions. The availability of direct-acting antivirals (DAAs) provides various treatment options for HIV/HCV coinfected patients, but the complexity of predicting and managing drug-drug interactions presents a unique challenge. Real-world experience or noninterventional studies can provide insight regarding the safety and use of therapeutics that may not be readily available from traditional clinical trials. This article provides a brief overview of the development of promising drugs for the treatment of CHC.

Trends in liver transplantation for hepatitis C in a country with reduced access to direct‐acting antiviral agents

“…In recent years, there has been an exponential development of HCV antiviral therapies of increasing efficacy: the first wave of medium‐efficacy regimens was represented by protease inhibitors in combination with pegylated interferon and ribavirin (triple therapy). More recently, highly effective and very well tolerated direct‐acting antiviral agents (DAA) have been approved …”

Nephrotoxicity Associated with Concomitant Use of Ledipasvir‐Sofosbuvir and Tenofovir in a Patient with Hepatitis C Virus and Human Immunodeficiency Virus Coinfection

“…Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) presents a therapeutic challenge for clinicians due to treatment‐related drug interactions and toxicities. Direct‐acting antivirals (DAAs) are the recommended therapy for all HCV genotypes and represent a major advantage over interferon‐based therapies because of their superior efficacy, convenient dosing regimen, low pill burden, and favorable adverse effect profile . Ledipasvir‐sofosbuvir (LDV‐SOF) is a commonly prescribed DAA combination for the treatment of genotype 1 HCV in patients with HIV coinfection, despite the fact that it interacts with tenofovir disoproxil fumarate (TDF), a first‐line antiretroviral drug .…”

“…Ó 2016 Pharmacotherapy Publications, Inc. C A S E R E P O R T represent a major advantage over interferonbased therapies because of their superior efficacy, convenient dosing regimen, low pill burden, and favorable adverse effect profile. [1][2][3] Ledipasvir-sofosbuvir (LDV-SOF) is a commonly prescribed DAA combination for the treatment of genotype 1 HCV in patients with HIV coinfection, despite the fact that it interacts with tenofovir disoproxil fumarate (TDF), a first-line antiretroviral drug. [3][4][5] This interaction results in increased systemic exposure to tenofovir, potentially increasing the risk of dose-related adverse effects including nephrotoxicity.…”

Public–Private Partnership: Targeting Real-World Data for Hepatitis C Direct-Acting Antivirals

“…By the time some of the postmarketing trials for these drugs were completed, the results were outdated because the HCV treatment landscape rapidly moved into the interferon-free era. 2 In such a rapidly evolving treatment landscape, innovative solutions are required to obtain "real-world data" at the earliest time points feasible.…”