Drug Interactions of Hepatitis C Direct-Acting Antivirals in the HIV-Infected Person

The development of direct-acting antivirals for hepatitis C has occurred at a rapid pace. Up to recently, HCV therapy has been limited to pegylated-interferon and ribavirin, but now physicians have several highly efficacious and well-tolerated interferon-free direct-acting antiviral agent (DAA) regimens available. In order to minimise patient harm and maximise the response to therapy, physicians must remain cognisant of the potential DAA drug-drug interactions in patients with HIV/HCV co-infection. HCV clearance needs to be achieved while maintaining HIV suppression and not compromising future antiretroviral options. CYP450 enzyme induction or inhibition accounts for many of the pharmacokinetic interactions between HCV DAA and HIV antiretrovirals, although an increasing number of transporter-mediated interactions are now recognised. DAA interactions in the HIV/HCV co-infected patient are largely extrapolated from drug-drug interaction studies with commonly used antiretrovirals. These studies then inform the selection of permitted antiretroviral regimens in phase II and III DAA clinical studies in HIV/HCV co-infection. We review the recently reported drug-drug interaction studies of HCV DAA therapy in the HIV-infected person and the HIV antiretroviral combinations in HCV DAA clinical trials.