Avoiding therapeutic pitfalls: The rational use of specifically targeted agents against hepatitis C infection

Abstract

The development of specifically targeted antiviral agents against hepatitis C is a major therapeutic advance that promises to markedly improve treatment response rates in patients with chronic infection. However, rapid emergence of drug resistance has already been described, the consequences of which are not yet understood. Although there are important differences between hepatitis C (HCV) and human immunodeficiency virus (HIV) infection, the judicious use of candidate agents against HCV should be guided by principles that have been established in the HIV therapeutic arena. In this review, we attempt to draw useful parallels between the development of antiretroviral therapy for HIV and preliminary data on antiviral agents for hepatitis C virus infection. Applying concepts learned in HIV therapeutics will hopefully lead to a prudent and cautious path in HCV treatment paradigms, particularly with respect to drug resistance. (HEPATOLOGY 2008;48:1700-1712

Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial

“…Research has focussed on therapies that inhibit hepatitis C virus proteins that are essential for intracellular replication; these drugs are referred to as direct-acting antiviral agents. 13 Boceprevir is a novel peptidomimetic NS3 protease inhibitor that forms a covalent reversible complex with the NS3 protease in vitro and has shown potent antiviral activity in the hepatitis C virus replicon system, and in patients who previously showed no response to peginterferon administered with or without ribavirin. 14,15 In a doseascending study in null responders, 16 boceprevir, when given in combination with peginterferon alfa-2b and ribavirin, was associated with a modest incremental haemoglobin reduction, as has been recorded with other direct-acting antiviral agents in the NS3 inhibitor class.…”

Hepatocellular carcinoma in HIV-infected patients comes of age: The convergence of epidemiology and treatment effectiveness

“…While increased delivery of HCV treatment could be expected to benefit individual patients, current therapy are likely to have only modest effects on the incidence of HCC in the short term. While HCV protease and/or polymerase inhibitors are expected to increase SVR rates in co-infected patients, studies of these agents have not been conducted and significant questions must be answered regarding drug-drug interactions, tolerability, and HCV drug resistance [32,33]. In addition, these drugs will be added to existing therapy with peginterferon and ribavirin which may serve to limit their use in HIV-infected patients with comorbid psychiatric disease and anemia.…”

New protease inhibitors for HCV – Help is on the way

“…For patients harboring infection with HCV-1, the predominant genotype worldwide, treatment with peginterferon and ribavirin produces sustained virologic response (SVR) in only 45% of patients and is limited by substantial side effects [1]. In the coming months, HCV therapy will enter a new era with the introduction of direct acting antiviral agents (DAAs) [2][3][4][5].…”