Tenofovir diphosphate and emtricitabine triphosphate concentrations in blood cells compared with isolated peripheral blood mononuclear cells: a new measure of antiretroviral adherence?

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 (ULPC) 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 five paired PBMC and ULPC samples over 6h. TFV-DP and FTC-TP concentrations were analyzed by liquid chromatography/mass spectrometry (LC-MS/MS). Partial areas under the curve (AUC) were calculated using noncompartmental methods and Spearman Rank Correlations (rho) between PBMC and ULPC were determined. RESULTS:: The median (25-75 percentile) concentration of TFV-DP in PBMCs was 143 (103-248) fmol/10 cells and in ULPC was 227 (160-394) fmol/10 cells (rho=0.65;p <0.0001). The concentration of FTC-TP in PBMCs was 6660 (5650-10000) fmol/10 cells and in ULPC was 19.0 (12.0-27.8) fmol/10 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 1 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 vs. consistent dosing. ULPC concentrations of TFV-DP and FTC-TP should be further investigated as a simply-collected, surrogate measure of ARV adherence