Tenofovir alafenamide (TAF) is preferred over tenofovir disoproxil fumarate (TDF) in HIV-positive patients with renal disease. The pharmacokinetic reason is:

• A TAF has higher renal clearance than TDF, reducing systemic exposure
• B TAF is not converted to tenofovir and acts via a separate mechanism
• C TAF is a more stable prodrug that delivers higher intracellular concentrations in lymphocytes at a lower plasma dose, reducing systemic (and renal) tenofovir exposure ✓
• D TAF undergoes biliary excretion exclusively, bypassing kidney clearance

Explanation

TAF is a novel prodrug that is more efficiently taken up into lymphocytes where it is activated intracellularly to tenofovir diphosphate. This means that equivalent antiviral efficacy is achieved at a plasma dose about 10-fold lower than TDF, resulting in substantially less systemic tenofovir exposure. Lower plasma tenofovir concentrations reduce proximal tubular (Fanconi syndrome) and bone (reduced BMD) toxicity associated with TDF. TAF and TDF both ultimately yield tenofovir as the active metabolite.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.