Which NRTI combination carries the highest risk of severe lactic acidosis and acute pancreatitis through mitochondrial DNA polymerase gamma inhibition?

• A Tenofovir plus emtricitabine
• B Abacavir plus lamivudine
• C Didanosine plus stavudine ✓
• D Zidovudine plus lamivudine

Explanation

Didanosine and stavudine are the two NRTIs most toxic to mitochondrial DNA polymerase gamma, and their combination produced well-documented clusters of fatal lactic acidosis, pancreatitis, and peripheral neuropathy, leading regulatory bodies to contraindicate their concurrent use. Both drugs have fallen out of favour for the same reason. Tenofovir's limiting toxicity is renal and skeletal, zidovudine causes marrow suppression and myopathy, and abacavir's concern is hypersensitivity, none of which is primarily mitochondrial.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.