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A 52-year-old male with HIV-1 infection and baseline eGFR of 55 mL/min/1.73m2 and early osteopenia is being switched from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). What pharmacokinetic characteristic of TAF accounts for its improved renal and bone safety profile compared to TDF?

TAF is more stable in plasma, delivering active drug intracellularly and resulting in 90% lower systemic plasma tenofovir exposure TAF is cleared exclusively by hepatic metabolism with no renal excretion TAF achieves higher plasma concentrations, which enhances renal tubular clearance TAF does not require intracellular phosphorylation to form active tenofovir diphosphate

Correct Answer:

TAF is more stable in plasma, delivering active drug intracellularly and resulting in 90% lower systemic plasma tenofovir exposure

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