Plasma and intracellular pharmacokinetics of tenofovir in patients switched from tenofovir disoproxil fumarate to tenofovir alafenamide. (27th March 2018)

• Record Type: Journal Article
• Authors: Podany, Anthony T.; Bares, Sara H.; Havens, Joshua; Dyavar, Shetty Ravi; O'Neill, Jennifer; Lee, Sarah; Fletcher, Courtney V.; Swindells, Susan; Scarsi, Kimberly K.
• Is Part Of: AIDS. Volume 32:Number 6(2018)
• Publication Date: 2018-03-27
• Subjects: antiretroviral therapy switch -- cell associated -- HIV infection -- pharmacokinetics -- tenofovir alafenamide -- tenofovir disoproxil fumarate; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000001744
• Languages: English
• ISSNs: 0269-9370

Abstract

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 6 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.