A patient with HIV/AIDS on first-line HAART develops peripheral neuropathy, lactic acidosis, and hepatic steatosis. The antiretroviral class most likely responsible is:

• A Integrase strand transfer inhibitors (INSTIs) such as raltegravir
• B Non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as efavirenz
• C Nucleoside reverse transcriptase inhibitors (NRTIs) such as stavudine (d4T) or didanosine (ddI) ✓
• D Protease inhibitors such as lopinavir

Explanation

Nucleoside/nucleotide RTIs (NRTIs) act as chain terminators of reverse transcriptase; they are also incorporated into mitochondrial DNA by mitochondrial DNA polymerase gamma, inhibiting it and causing mitochondrial dysfunction. This class effect, most pronounced with thymidine analogue NRTIs (stavudine, didanosine, zidovudine), produces the NRTI mitochondrial toxicity syndrome: peripheral neuropathy, lactic acidosis with hepatic steatosis, lipodystrophy, and myopathy. Newer NRTIs (tenofovir, emtricitabine) have much lower mitochondrial toxicity.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.