Drug interactions in HIV-infected patients treated for hepatitis C

ABSTRACT

Introduction: The introduction of direct-acting antivirals (DAA) has revolutionized the hepatitis C field. Most hepatitis C patients can now be cured, including those coinfected with HIV. However, drug-drug interactions (DDI) between DAA and antiretrovirals (ARV) should be known to prevent either toxicity due to drug overexposure or treatment failures due to low drug concentrations.

Areas covered: Clinically significant DDI may be classified as major (when co-administration should be contraindicated) or minor (when they require close monitoring, changes in drug dosage or in timing). Strategies for preventing and managing DDI influence response rates in HIV/HCV-coinfected patients. Pharmacokinetic evidence of interactions from clinical trials and reports from real-world experience are discussed.

Expert opinion: The most frequent DDI between DAA and ARV affect drug metabolism by CYP450 induction/inhibition, leading to abnormal drug exposures. Throughout this mechanism interact HCV and HIV boosted protease inhibitors, and most non-nucleoside HCV and HIV polymerase inhibitors. In contrast, HIV and HCV nucleos(t)ide analogue polymerase inhibitors, most HCV NS5A inhibitors and HIV integrase inhibitors (e.g., dolutegravir), do not or only marginally affect CYP450, and therefore are relatively free of DDI. Exposure to some HIV and HCV nucleos(t)ide analogues (e.g., tenofovir and sofosbuvir, respectively) is subject to induction/inhibition of drug transporters (e.g., P-glycoprotein) and requires special attention in patients with renal insufficiency.

KEYWORDS:

• Sofosbuvir
• daclatasvir
• dolutegravir
• HIV
• HCV
• antiretroviral therapy
• drug interactions
• elbasvir
• grazoprevir
• velpatasvir

Article highlights

• Interactions between DAA and ARV may lead to toxicity due to drug overexposure or treatment failure due to suboptimal drug concentrations. Prior knowledge of DDI may help to prevent their harmful effects in clinical practice.

• The most common DDI are due to CYP450 induction or inhibition, and are mainly produced by HCV and HIV protease inhibitors, especially when co-formulated with ritonavir or cobicistat as pharmacoenhancers, and most non-nucleoside analogue HCV or HIV polymerase inhibitors.

• HIV and HCV nucleos(t)ide analogue polymerase inhibitors, and most HCV NS5A inhibitors and HIV integrase inhibitors (e.g., dolutegravir), do not or only marginally affect CYP450, and therefore are free of clinically significant DDI.

• The main caution using nucleos(t)ide analogues (e.g., sofosbuvir for HCV and tenofovir for HIV) is the induction/inhibition of drug transporters, such as P-glycoprotein, specially in patients with renal insufficiency.

• The relatively short length of hepatitis C treatment (from 8 to 24 weeks) makes DDI relatively easy to manage. When DAA options are limited, antiretroviral drug switching for a short period can always prevent potential harmful DDI.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported in part by grants from Instituto de Salud Carlos III (project nos. ICI14-00372, CES12/003, PI13/01574) and Fundación Investigación y Educación en Sida (IES).