Tenofovir Levels in Blood 4-Fold Higher With TAF Than TDF
July 28, 2016
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).
Mark Mascolini writes about HIV infection.
This article was provided by TheBodyPRO. It is a part of the publication ASM Microbe 2016.
Add Your Comment:
(Please note: Your name and comment will be public, and may even show up in
Internet search results. Be careful when providing personal information! Before
adding your comment, please read TheBody.com's Comment Policy.)
The content on this page is free of advertiser influence and was produced by our editorial team. See our content and advertising policies.