A patient with HIV on ART (TDF + FTC + efavirenz) has an undetectable viral load but develops persistent virological failure (VL >1000 copies/mL) after 2 years. Resistance testing shows K65R mutation. This mutation causes resistance to:

• A Efavirenz and nevirapine (NNRTIs) by altering the NNRTI binding pocket
• B Both TDF and 3TC/FTC equally, but has no effect on abacavir
• C Protease inhibitors by altering the Gag-Pol cleavage site substrate
• D Tenofovir disoproxil fumarate (TDF) and also reduces susceptibility to most other NRTIs except zidovudine ✓

Explanation

The K65R mutation (lysine to arginine at position 65 of reverse transcriptase) is selected by tenofovir and reduces susceptibility to tenofovir, didanosine (ddI), stavudine (d4T), and abacavir—most NRTIs that do not include thymidine analogs. Importantly, K65R actually hypersensitizes HIV to zidovudine (AZT) by a mechanism involving slowed incorporation of zidovudine triphosphate being more favorable than for other NRTIs. It does not confer resistance to NNRTIs or protease inhibitors. The M184V mutation (from FTC/3TC) has complex interactions with K65R: M184V reduces K65R's impact on tenofovir susceptibility when both are present.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.