Drug interactions between antiretrovirals and new or emerging direct-acting antivirals in HIV/hepatitis C virus coinfection

Karageorgopoulos, Drosos E.^a,*; El-Sherif, Omar^b,*; Bhagani, Sanjay^a,c; Khoo, Saye H.^d

^aDepartment of Infectious Diseases/HIV Medicine, Royal Free London NHS Foundation Trust, London, UK

^bSt. James's Hospital, Dublin, Ireland

^cResearch Department of Infection, UCL, London

^dDepartment of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK

^*Dr Drosos E. Karageorgopoulos and Dr Omar El-Sherif contributed equally to the writing of this article.

Correspondence to Dr Sanjay Bhagani, BSc, MB, ChB, FRCP, Department of Infectious Diseases/HIV Medicine, The Royal Free Hospital, Pond Street, London NW3 2QG, UK. Tel: +44 20 7794 0500 x36285; fax: +44 20 7830 2730; e-mail:[email protected]

Current Opinion in Infectious Diseases27(1):p 36-45, February 2014. |DOI:10.1097/QCO.0000000000000034

Abstract

Purpose of review

We reviewed the pharmacokinetic interactions between direct-acting antivirals against hepatitis C virus (HCV) and antiretroviral agents.

Recent findings

Most relevant pharmacokinetic studies involve healthy individuals and refer to the already licensed HCV protease inhibitors, boceprevir and telaprevir. Data from a phase II clinical trial question the clinical relevance of the interactions between boceprevir and HIV protease inhibitors. The use of a higher dose of telaprevir appears to offset the effect of efavirenz on telaprevir metabolism according to another phase II trial. Boceprevir and particularly telaprevir substantially increase the exposure to maraviroc, similarly to other potent CYP3A4 inhibitors. Different dosages of faldaprevir and daclatasvir have been recommended to be used in combination with a boosted HIV protease inhibitor vs. an efavirenz-based antiretroviral regimen. HIV protease inhibitors appear to substantially increase the exposure to simeprevir. The interactions between sofosbuvir and most antiretroviral agents do not appear to be of clinical relevance or to require dosage modifications.

Summary

The drug–drug interaction studies for HCV direct-acting antivirals and antiretrovirals are important in determining the appropriate drug combinations and dosages. The clinical implications of these interactions need further assessment in different categories of patients, including those with cirrhosis.