Tenofovir Levels in Blood 4-Fold Higher With TAF Than TDF

Tenofovir-diphosphate (TFV-DP) levels in peripheral blood mononuclear cells (PBMCs) were four-fold higher with tenofovir alafenamide (TAF) than with tenofovir disoproxil fumarate (TDF) in a randomized, double-blind switch study. More than 90% of patients in the TAF arm and the continued TDF arm kept a viral load below 50 copies/mL through 48 weeks, according to the study.

Emtricitabine (FTC) is coformulated with TAF (Descovy) at two dosage strengths -- 200/25 mg and 200/10 mg -- as a double-drug backbone for use with a third agent. The 200/10-mg dose is intended for use with ritonavir (Norvir)- or cobicistat (Tybost)-boosted protease inhibitors (PIs). TAF is metabolized in PBMCs, macrophages and hepatocytes to tenofovir, which is phosphorylated to the active metabolite TFV-DP.

This analysis compared TFV-DP concentrations in PBMCs with TAF versus TDF in a randomized, double-blind trial of virologically suppressed patients taking a regimen containing TDF/FTC. The trial randomized 663 participants 1:1 to switch to TAF/FTC or to continue TDF/FTC while keeping the same third agent. Researchers collected blood samples after four weeks of treatment to measure intracellular TFV-DP in PBMCs.

Respectively, the TAF and TDF groups had median ages of 48 and 49 years, 14% and 16% were women, 73% and 77% white and 21% and 20% black. Median CD4 counts stood at 663 and 624 cells/mm3 in the TAF and TDF groups, and median estimated glomerular filtration rates at 99 and 100 mL/min. Proportions of participants taking a boosted PI were 47% in the TAF arm and 45% in the TDF arm.

After 48 weeks, 94% randomized to TAF and 93% randomized to TDF maintained a viral load below 50 copies/mL. The researchers measured TFV-DP in PBMCs in 304 people taking TAF/FTC and 265 taking TDF/FTC. TFV-DP in PBMCs averaged 114 pg/million cells with TAF and 27.8 pg/million cells with TDF. The resulting ratio of the geometric least-squares means (GMR) of 416% (90% confidence interval 362% to 477%) indicated that TAF yielded four-fold higher TFV-DP levels in PBMCs than TDF. Depending on the third antiretroviral in the regimen, GMR ranged from 1.7- to 9.5-fold higher with TAF than with TDF.

The researchers conclude that TAF provides enhanced delivery of TFV into PBMCs compared with TDF. They note that results are consistent with TFV-DP exposure in PBMCs when using TAF as a 25-mg single agent or at 10 mg as part of coformulated elvitegravir/cobicistat/TAF/FTC (Genvoya).