Urine Assay to Measure Tenofovir Concentrations in Patients Taking Tenofovir Alafenamide

Linden Lalley-Chareczko, Emily Hiserodt, Ganesh Moorthy, Athena Zuppa, Karam Mounzer, Helen Koenig, Linden Lalley-Chareczko, Emily Hiserodt, Ganesh Moorthy, Athena Zuppa, Karam Mounzer, Helen Koenig

Abstract

Background: HIV pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine is effective when taken daily. Previously, we developed a urine assay capable of detecting the prodrug tenofovir (TFV) in patients taking tenofovir disoproxil fumarate (TDF)-based PrEP. However, tenofovir alafenamide (TAF) has replaced TDF due to its different safety profile for HIV treatment and was recently approved as PrEP. Given the need to ensure the aforementioned assay remains available for the purpose of objective adherence monitoring, it is critical to ensure its accuracy for detecting TFV in patients taking TAF. Methods: Blood and urine samples were collected from 3 cohorts of patients: (1) 10 participants living with HIV (PLWH) with suppressed virus on a TAF-based regimen, (2) 10 HIV-participants administered 1 dose of TAF/FTC followed by urine and plasma sampling for 7 days starting 1-3 h post-dose, and (3) 10 HIV-participants administered 7 doses of TAF/FTC followed by urine and plasma sampling for 10 days starting 1-3 h after the last dose. Samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with high sensitivity and specificity for TFV. HIV-samples were compared to a historical cohort administered one dose of TDF/FTC. Results: PLWH were 90% male, 40% African American, and 10% Hispanic (mean age = 57 y; SD 8.88 y). HIV-participants were 55% male and 70% Caucasian (mean age = 31.6 y; SD 7.70 y). Samples from PLWH demonstrated TFV concentrations 2 logs higher in urine than plasma (1,000 ng/mL vs ±10 ng/mL) at the time of collection. Urine samples following a single dose of TAF in HIV-participants yielded TFV concentrations ranging from 100 to 1,000 ng/mL 1-3 h post-dose and remained >100 ng/mL for 6 days in 8 of 10 participants. Urine samples collected after 7 consecutive doses of TAF yielded TFV concentrations >1,000 ng/mL 1-3 h after dosing discontinuation, with TFV concentrations >1,00 ng/mL 7 days post discontinuation in 8 of 10 participants. Urine TFV concentrations following TAF administration were comparable to those from a historical cohort administered TDF/FTC. Plasma TFV concentrations were low(±10 ng/mL) in both HIV-cohorts at all time points. Conclusions: TFV persists in urine at detectable concentrations in participants taking TAF/FTC for at least 7 days despite largely undetectable plasma concentrations, with urine TFV concentrations comparable to patients taking TDF/FTC. This study demonstrates the ability of a urine TFV assay to measure recent TAF adherence.

Keywords: HIV - human immunodeficiency virus; PrEP; tenofovir; tenofovir alafenamide (TAF); therapaeutic drug monitoring.

Copyright © 2020 Lalley-Chareczko, Hiserodt, Moorthy, Zuppa, Mounzer and Koenig.

Figures

Figure 1
Figure 1
Cohort 1: Relationship between urine and plasma TFV concentrations in PLWH taking daily TAF. TFV, tenofovir; PLWH, Participants Living with HIV; TAF, tenofovir alafenamide; ng/mL, nanograms per millimeter.
Figure 2
Figure 2
Cohor t 2: Urine/Plasma TFV Concentrations following a Single Dose of FTC/TAF in 10 HIV-Participants. TFV, tenofovir; FTC/TAF, emtricitabine/tenofovir alafenamide; TAF, tenofovir alafenamide; ng/mL, nanograms per millimeter.
Figure 3
Figure 3
Urine/Plasma TFV concentrations after a single dose of FTC/TAF in 10 HIV-subjects, with comparison to historical cohort of subjects given a single dose of FTC/TDF. TFV, tenofovir; FTC/TAF, emtricitabine/tenofovir alafenamide; HIV–, Human Immunodeficiency Virus-Negative; FTC/TDF: emtricitabine/tenofovir disoproxil fumarate; TDF, tenofovir disoproxil fumarate; TAF, tenofovir alafenamide; ng/mL, nanograms per millimeter.
Figure 4
Figure 4
Cohort 3: Urine TFV Concentrations following 7 consecutive doses of FTC/TAF in 10 HIV-subjects. TFV, tenofovir; FTC/TAF, emtricitabine/tenofovir alafenamide; HIV–, Human Immunodeficiency Virus-Negative; TAF, tenofovir alafenamide; ng/mL, nanograms per millimeter.

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