Nucleoside analogues and mitochondrial toxicity

Area of Science:

• Hepatology
• Infectious Diseases
• Pharmacovigilance

Background:

• Coinfection with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV) is common.
• Antiretroviral therapy and antiviral treatments for HCV can have overlapping toxicities.
• Mitochondrial toxicity is a known concern with certain nucleoside reverse transcriptase inhibitors.

Purpose of the Study:

• To evaluate the risk of adverse events in patients with HIV and HCV coinfection receiving specific treatment regimens.
• To identify potential drug-drug interactions leading to increased toxicity.
• To inform clinical practice and regulatory actions regarding medication safety.

Main Methods:

• Analysis of the US Food and Drug Administration's Adverse Event Reporting System (AERS) database.
• Identification of patients coinfected with HIV and HCV.
• Review of adverse events associated with ribavirin and didanosine, with or without stavudine treatment.

Main Results:

• Coinfection patients on ribavirin and didanosine (with or without stavudine) showed a higher risk of mitochondrial toxicity.
• Observed adverse events included fatal hepatic failure, peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis.
• The US product labels for didanosine and ribavirin were updated to warn against this combination.

Conclusions:

• Coadministration of ribavirin and didanosine poses a significant risk of severe mitochondrial toxicity in HIV/HCV coinfected patients.
• Healthcare providers should exercise caution and consider alternative regimens.
• Regulatory action was taken to enhance patient safety through revised drug labeling.