Skip Navigation LinksHome > March 1, 2013 - Volume 62 - Issue 3 > Tenofovir Diphosphate and Emtricitabine Triphosphate Concent...
JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e3182794723
Basic and Translational Science

Tenofovir Diphosphate and Emtricitabine Triphosphate Concentrations in Blood Cells Compared With Isolated Peripheral Blood Mononuclear Cells: A New Measure of Antiretroviral Adherence?

Adams, Jessica L. PharmD, BCPS*; Sykes, Craig MSc*; Menezes, Prema PhD; Prince, Heather M.A. PA-C; Patterson, Kristine B. MD; Fransen, Katrien MSc; Crucitti, Tania PharmD, Clin Biol, PhD; De Baetselier, Irith MSc; Van Damme, Lut MD, PhD§; Kashuba, Angela D.M. BScPhm, PharmD, DABCP*,†

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Background: The active metabolites of tenofovir (TFV) and emtricitabine (FTC) in peripheral blood mononuclear cells (PBMCs) have been used as markers of long-term antiretroviral (ARV) adherence. However, the process of isolating PBMCs is expensive, complex, and not feasible in many settings. We compared concentrations of TFV-diphosphate (TFV-DP) and FTC-triphosphate (FTC-TP) in the upper layer packed cells (ULPCs) obtained after whole blood centrifugation to isolated PBMCs as a possible alternative marker of adherence.

Methods: Ten HIV+ adults with HIV RNA <50 copies/mL on a TDF/FTC-containing regimen provided 5 paired PBMC and ULPC samples over 6 hours. TFV-DP and FTC-TP concentrations were analyzed by liquid chromatography/mass spectrometry. Partial areas under the curve were calculated using noncompartmental methods and Spearman Rank Correlations (rho) between PBMC and ULPC were determined.

Results: The median (25th–75th percentile) concentration of TFV-DP in PBMCs was 143 (103–248) fmol/106 cells and in ULPC was 227 (160–394) fmol/106 cells (rho = 0.65; P < 0.0001). The concentration of FTC-TP in PBMCs was 6660 (5650–10,000) fmol/106 cells and in ULPC was 19.0 (12.0–27.8) fmol/106 cells (rho = 0.55; P < 0.0001). Compared to PBMCs, ULPC TFV-DP was 64% higher and FTC-TP was 99.7% lower. ULPC concentrations of TFV-DP and FTC-TP in one additional subject receiving a single dose of TDF/FTC were only 0.05% and 25%, of the other 10 subjects, respectively.

Conclusions: ULPC concentrations significantly correlated with PBMC concentrations. Preliminary single-dose data suggest some discrimination between intermittent versus consistent dosing. ULPC concentrations of TFV-DP and FTC-TP should be further investigated as a simply collected surrogate measure of ARV adherence.

© 2013 Lippincott Williams & Wilkins, Inc.


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