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. 2018 Mar 27;32(6):761-765.
doi: 10.1097/QAD.0000000000001744.

Plasma and intracellular pharmacokinetics of tenofovir in patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide

Anthony T Podany  1 , Sara H Bares  2 , Joshua Havens  2 , Shetty Ravi Dyavar  1 , Jennifer O'Neill  2 , Sarah Lee  3 , Courtney V Fletcher  1   2 , Susan Swindells  2 , Kimberly K Scarsi  1   2
Affiliations

Plasma and intracellular pharmacokinetics of tenofovir in patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide

Anthony T Podany et al. AIDS. .

Abstract

Objectives: The aim of the study was to compare the intraindividual plasma and intracellular peripheral blood mononuclear cell (PBMC) pharmacokinetics of tenofovir (TFV) and its intracellular metabolite, TFV-diphosphate (TFV-DP) in patients switched from a fixed-dose combination (FDC) tablet of TFV disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir (EVG)/cobicistat (COBI) to a FDC containing TFV alafenamide (TAF)/FTC/EVG/COBI.

Design: A single-arm, prospective, nonrandomized, cross-over, pharmacokinetic study in patients receiving a TDF-containing regimen (TDF 300 mg/FTC 200 mg/EVG 150 mg/COBI 150 mg) switched to a TAF-containing FDC regimen (TAF 10 mg/FTC 200 mg/EVG 150 mg/COBI 150 mg).

Methods: Single, sparse plasma and PBMC samples were collected during TDF therapy and 4-8 weeks post-switch to the TAF-containing regimen. Plasma TFV and cell associated TFV-DP concentrations were determined with validated liquid chromatography tandem mass spectrometry methods. PBMC cell enumeration was performed by quantification of RNaseP (RPP30) gene copy numbers using a highly sensitive droplet digital PCR assay. Plasma and PBMC pharmacokinetics were summarized as geometric mean and compared as a geometric mean ratio with a Wilcoxon signed-rank test.

Results: In 30 participants with evaluable data, TFV plasma concentrations decreased 90% [TDF: 99.98 (2.24) ng/ml vs. TAF: 10.2 (1.6) ng/ml, P < 0.001] after the switch while cell-associated TFV-DP increased 2.41-fold [TAF: 834.7 (2.49) vs. TDF: 346.85 (3.75) fmol/10 cells, P = 0.004].

Conclusion: Intraindividually, plasma TFV concentrations significantly decreased while cell associated TFV-DP concentrations significantly increased after switching from a TDF to a TAF-containing antiretroviral therapy regimen.

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Conflict of interest statement

Conflicts of Interest

The remaining authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Whisker plot of plasma tenofovir and PBMC tenofovir diphosphate concentrations during TDF and TAF based dosing. Data presented as 25th, 50th and 75th percentiles.
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References

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