Tenofovir alafenamide (TAF) has largely replaced tenofovir disoproxil fumarate (TDF) in HIV regimens because:
- A TAF targets integrase instead of reverse transcriptase, providing a mechanism distinct from TDF
- B TAF has a longer plasma half-life enabling monthly dosing compared to TDF's daily requirement
- C TAF is a prodrug that delivers higher intracellular tenofovir diphosphate concentrations in lymphocytes at 10-fold lower plasma levels, reducing renal and bone toxicity ✓
- D TAF does not require intracellular phosphorylation to become active, unlike TDF
Correct answer: C. TAF is a prodrug that delivers higher intracellular tenofovir diphosphate concentrations in lymphocytes at 10-fold lower plasma levels, reducing renal and bone toxicity
Explanation
TAF is a stable prodrug phosphonamidate that is taken up efficiently by lymphocytes (the HIV reservoir), where intracellular esterases convert it to tenofovir, which is then phosphorylated to the active tenofovir diphosphate (TFV-DP). This targeted lymphocyte delivery gives equivalent antiviral activity at approximately 10-fold lower plasma tenofovir concentrations compared to TDF, markedly reducing renal tubular toxicity (Fanconi syndrome risk) and bone mineral density loss.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.