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Tenofovir diphosphate and emtricitabine triphosphate concentrations in blood cells compared with isolated peripheral blood mononuclear cells: a new measure of antiretroviral adherence?
J Acquir Immune Defic Syndr. 2013 Mar 01; 62(3):260-6.JA

Abstract

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/10(6) cells and in ULPC was 227 (160-394) fmol/10(6) cells (rho = 0.65; P < 0.0001). The concentration of FTC-TP in PBMCs was 6660 (5650-10,000) fmol/10(6) cells and in ULPC was 19.0 (12.0-27.8) fmol/10(6) 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.

Authors+Show Affiliations

Department of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23111578

Citation

Adams, Jessica L., et al. "Tenofovir Diphosphate and Emtricitabine Triphosphate Concentrations in Blood Cells Compared With Isolated Peripheral Blood Mononuclear Cells: a New Measure of Antiretroviral Adherence?" Journal of Acquired Immune Deficiency Syndromes (1999), vol. 62, no. 3, 2013, pp. 260-6.
Adams JL, Sykes C, Menezes P, et al. Tenofovir diphosphate and emtricitabine triphosphate concentrations in blood cells compared with isolated peripheral blood mononuclear cells: a new measure of antiretroviral adherence? J Acquir Immune Defic Syndr. 2013;62(3):260-6.
Adams, J. L., Sykes, C., Menezes, P., Prince, H. M., Patterson, K. B., Fransen, K., Crucitti, T., De Baetselier, I., Van Damme, L., & Kashuba, A. D. (2013). Tenofovir diphosphate and emtricitabine triphosphate concentrations in blood cells compared with isolated peripheral blood mononuclear cells: a new measure of antiretroviral adherence? Journal of Acquired Immune Deficiency Syndromes (1999), 62(3), 260-6. https://doi.org/10.1097/QAI.0b013e3182794723
Adams JL, et al. Tenofovir Diphosphate and Emtricitabine Triphosphate Concentrations in Blood Cells Compared With Isolated Peripheral Blood Mononuclear Cells: a New Measure of Antiretroviral Adherence. J Acquir Immune Defic Syndr. 2013 Mar 1;62(3):260-6. PubMed PMID: 23111578.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tenofovir diphosphate and emtricitabine triphosphate concentrations in blood cells compared with isolated peripheral blood mononuclear cells: a new measure of antiretroviral adherence? AU - Adams,Jessica L, AU - Sykes,Craig, AU - Menezes,Prema, AU - Prince,Heather M A, AU - Patterson,Kristine B, AU - Fransen,Katrien, AU - Crucitti,Tania, AU - De Baetselier,Irith, AU - Van Damme,Lut, AU - Kashuba,Angela D M, PY - 2012/11/1/entrez PY - 2012/11/1/pubmed PY - 2013/8/21/medline SP - 260 EP - 6 JF - Journal of acquired immune deficiency syndromes (1999) JO - J. Acquir. Immune Defic. Syndr. VL - 62 IS - 3 N2 - 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/10(6) cells and in ULPC was 227 (160-394) fmol/10(6) cells (rho = 0.65; P < 0.0001). The concentration of FTC-TP in PBMCs was 6660 (5650-10,000) fmol/10(6) cells and in ULPC was 19.0 (12.0-27.8) fmol/10(6) 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. SN - 1944-7884 UR - https://www.unboundmedicine.com/medline/citation/23111578/Tenofovir_diphosphate_and_emtricitabine_triphosphate_concentrations_in_blood_cells_compared_with_isolated_peripheral_blood_mononuclear_cells:_a_new_measure_of_antiretroviral_adherence L2 - http://dx.doi.org/10.1097/QAI.0b013e3182794723 DB - PRIME DP - Unbound Medicine ER -