Urine assay for tenofovir to monitor adherence in real time to tenofovir disoproxil fumarate/emtricitabine as pre‐exposure prophylaxis

Objectives Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is approved for pre‐exposure prophylaxis (PrEP) against HIV infection. Adherence is critical for the success of PrEP, but current adherence measurements are inadequate for real‐time adherence monitoring. We developed and validated a ur...

Full description

Saved in:

Bibliographic Details
Published in:	HIV medicine Vol. 18; no. 6; pp. 412 - 418
Main Authors:	Koenig, HC, Mounzer, K, Daughtridge, GW, Sloan, CE, Lalley‐Chareczko, L, Moorthy, GS, Conyngham, SC, Zuppa, AF, Montaner, LJ, Tebas, P
Format:	Journal Article
Language:	English
Published:	England Wiley Subscription Services, Inc 01-07-2017
Subjects:	adherence Adhesion Adult Antiviral Agents - administration & dosage Antiviral Agents - therapeutic use Assaying Categories Chromatography, Liquid Drug Administration Schedule Emtricitabine Emtricitabine - administration & dosage Emtricitabine - therapeutic use Exposure Female High performance liquid chromatography HIV HIV Infections - prevention & control HIV prevention Human immunodeficiency virus Humans Infections Liquid chromatography Male Mass spectrometry Mass spectroscopy Medication Adherence Middle Aged Pilot Projects Plasma levels Pre-Exposure Prophylaxis Prophylaxis Real time Sensitivity Tandem Mass Spectrometry Tenofovir Tenofovir - administration & dosage Tenofovir - therapeutic use Tenofovir - urine Truvada Urine urine tenofovir assay Young Adult pre-exposure prophylaxis HIV prevention Truvada adherence urine tenofovir assay
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Objectives Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is approved for pre‐exposure prophylaxis (PrEP) against HIV infection. Adherence is critical for the success of PrEP, but current adherence measurements are inadequate for real‐time adherence monitoring. We developed and validated a urine assay to measure tenofovir (TFV) to objectively monitor adherence to PrEP. Methods We developed a urine assay using high‐performance liquid chromatography coupled to tandem mass spectrometry with high sensitivity/specificity for TFV that allowed us to determine TFV concentrations in log10 categories between 0 and 10 000 ng/mL. We validated the assay in three cohorts: (1) HIV‐positive subjects with undetectable viral loads on a TDF/FTC‐based regimen, (2) healthy HIV‐negative subjects who received a single dose of TDF/FTC, and (3) HIV‐negative subjects receiving daily TDF/FTC as PrEP for 24 weeks. Results The urine assay detected TFV with greater sensitivity than plasma‐based measures and with a window of measurements within 7 days of the last TDF/FTC dose. Based on the urine log‐linear clearance after the last dose and its concordance with all detectable plasma levels, a urine TFV concentration > 1000 ng/mL was identified as highly predictive of the presence of TFV in plasma at > 10 ng/mL. The urine assay was able to distinguish high and low adherence patterns within the last 48 h (> 1000 ng/mL versus 10–1000 ng/mL), as well as nonadherence (< 10 ng/mL) extended over at least 1 week prior to measurement. Conclusions We provide proof of concept that a semiquantitative urine assay measuring levels of TFV could be further developed into a point‐of‐care test and be a useful tool to monitor adherence to PrEP.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1464-2662 1468-1293
DOI:	10.1111/hiv.12518