Directly acting antivirals for hepatitis C and antiretrovirals: potential for drug–drug interactions - Introduction

A Special Author Introduction
Current Opinion in HIV and AIDS

ISSN: 1746-630X • Frequency: 6/year • Subscribe Now • Journal Website

By Kay Seden

It is estimated that approximately 130-210 million individuals, representing 3% of the world population, are chronically infected with hepatitis C virus (HCV), with prevalence that varies markedly between populations.  The recent licensing of the directly acting antivirals (DAAs) boceprevir and telaprevir represents a new paradigm for the treatment of HCV. Conventional treatment with combinations of ribavirin and pegylated interferon (PEG-IFN) have been found to achieve a sustained virological response (SVR) in only 36%–46% of patients with HCV genotype 1 monoinfection, when treated for 48 weeks.  As a result of the limited success rates of conventional therapy, a vast number of HCV infected patients who were not previously treated successfully, are set to benefit from the advent of the current drugs and also the many drugs that are in the clinical development pipeline. Eventually, HCV treatment may involve a combination of DAA agents, without the requirement for PEG-IFN or ribavirin treatment. 
The licensing of novel agents however brings specific challenges, and drug-drug interactions (DDI) are likely to be a major consideration when treating patients with DAA, especially patients co-infected with HIV who are taking antiretroviral regimens. HIV-positive patients who are receiving antiretrovirals are relatively highly represented among those with HCV infection, and are at high risk of DDI. Targeted pharmacokinetic drug interaction studies have demonstrated that both boceprevir and telaprevir are potent inhibitors of the metabolic enzyme cytochrome P4503A4, making them perpetrators of interactions with co-administered medications which are metabolised by this enzyme. In addition, co-administered medications may affect plasma levels of boceprevir and telaprevir via various mechanisms, some of which remain to be fully elucidated.
This review aims to provide a comprehensive summary of DDI expected with the recently licensed DAAs and antiretrovirals, including pharmacokinetic data where available. In addition, interaction data for telaprevir and boceprevir with other co-medications and recommendations made by the manufacturers of the newly licensed drugs are summarised along with discussion on the potential for DDI with the DAA in clinical development and the mechanisms of interaction.

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