Urine Tenofovir Concentrations Correlate With Plasma and Relate to Tenofovir Disoproxil Fumarate Adherence: A Randomized, Directly Observed Pharmacokinetic Trial (TARGET Study)

Clin Infect Dis. 2020 May 6;70(10):2143-2151. doi: 10.1093/cid/ciz645.

Abstract

Background: Direct measurement of tenofovir (TFV) in urine could be an objective measure to monitor adherence to preexposure prophylaxis (PrEP) or TFV-based antiretroviral therapy (ART).

Methods: We conducted a 3-arm randomized, pharmacokinetic study of tenofovir disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg among adults living with human immunodeficiency virus. Participants were randomized to receive controlled TDF/FTC dosing as (1) "perfect" adherence (daily); (2) "moderate" adherence (4 doses/week); or (3) "low" adherence (2 doses/week). We obtained trough spot urine and plasma samples during a 6-week directly observed therapy period and a 4-week washout period. TFV concentrations were compared between adherence arms using 1-way analysis of variance.

Results: Among 28 participants, the median age was 33 years and 16 (57%) were male. Correlation between TFV plasma and urine concentrations was strong (ρ = 0.78; P < .0001). Median (interquartile range) steady-state trough TFV concentrations (ng/mL) for perfect, moderate, and low TDF adherence were 41 (26-52), 16 (14-19), and 4 (3-5) in plasma; and 6480 (3940-14 300), 3405 (2210-5020), and 448 (228-675) in urine. Trough TFV concentrations at steady state were significantly different between the 3 adherence arms for plasma (P < .0001) and urine (P = .0002). Following drug cessation, TFV concentrations persisted longer in urine than plasma samples. Washout urine TFV concentrations and time to undetectable concentrations did not differ between the 3 randomized adherence groups.

Conclusions: Urine TFV concentrations can inform interpretation of novel point-of-care urine-based TFV assays to assess recent TDF adherence.

Clinical trials registration: NCT03012607

Trial registration: ClinicalTrials.gov NCT03012607 NCT03012607 NCT00301260.

Keywords: HIV; antiretroviral treatment; directly observed therapy; preexposure prophylaxis; tenofovir.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-HIV Agents* / therapeutic use
  • Emtricitabine / therapeutic use
  • HIV Infections* / drug therapy
  • Humans
  • Male
  • Pharmaceutical Preparations*
  • Plasma
  • Pre-Exposure Prophylaxis*
  • Tenofovir* / therapeutic use

Substances

  • Anti-HIV Agents
  • Pharmaceutical Preparations
  • Tenofovir
  • Emtricitabine

Associated data

  • ClinicalTrials.gov/NCT03012607
  • ClinicalTrials.gov/NCT03012607
  • ClinicalTrials.gov/NCT00301260