Brief Report: No Difference in Urine Tenofovir Levels in Patients Living With HIV on Unboosted Versus Dose-Adjusted Boosted Tenofovir Alafenamide

Abstract

Background: Tenofovir alafenamide (TAF) is increasingly used in HIV treatment, with or without agents that require pharmacologic boosters such as ritonavir/cobicistat. Boosters increase TAF levels, so the TAF dose is lowered in single-pill combinations. We hypothesized that individuals on dose-adjusted boosted TAF would have similar urine tenofovir (TFV) concentrations to those on unboosted TAF.Setting/Methods: We collected urine samples from patients with HIV on TAF, with evidence of virologic suppression and high selfreported adherence at 2 San Francisco clinics from June 2019 to January 2020. We measured urine TFV levels by liquid chromatography/tandem mass spectrometry and used linear regression to compare natural log-transformed urine TFV levels for patients on boosted versus unboosted TAF.Results: Our analysis included 30 patients on unboosted TAF (25 mg daily TAF) and 15 on boosted TAF (12 on 10 mg daily TAF and 3 on 25 mg daily TAF). Patients on unboosted vs. boosted TAF had similar baseline age, weight, sex, and creatinine. In unadjusted univariate linear regression, there were no significant differences in urine TFV levels based on presence/absence of boosting after TAF dose reduction to 10 mg (geometric mean ratio 1.07; 95% confidence interval: 0.53 to 2.16). This finding was unchanged in adjusted analysis.Conclusions: No significant differences in urine TFV levels were seen for patients on unboosted vs. boosted dose-reduced TAF. These results have important implications for our forthcoming point-of-care urine immunoassay for TAF, implying that separate adherence cutoffs will not be necessary for patients on boosters and dose-reduced TAF. A single POC TAF immunoassay will, thus, support monitoring on most TAF-based antiretroviral therapy.

Urine Tenofovir Levels Strongly Correlate With Virologic Suppression in Patients With Human Immunodeficiency Virus on Tenofovir Alafenamide-Based Antiretroviral Therapy

“…Because self-reported ART adherence was high (with objective adherence metrics shown to be more reliable than self-report [9]), the availability of a POC tool to objectively measure adherence for patients on TFV-based regimens is useful. In settings in which frequent RNA monitoring is not feasible because of cost or access, POC testing could help clarify when virologic failures are more likely attributable to nonadherence (prompting interventions) or to resistance, requiring genotyping and potential ART change [9][10][11]. Even in settings in which frequent RNA checks are feasible, results are often not available in real time.…”

“…To enrich our sample for individuals with adherence challenges, participants from POP-UP (a clinic serving patients with homelessness/unstable housing [8], embedded within 1 of our sites) received proactive outreach. Because we previously demonstrated that individuals have similar urine TFV concentrations on TAF whether dosed at 25 mg or 10 mg (with pharmacologic boosters) [9], we did not exclude participants based on TAF formulation. Urine TFV levels were measured by liquid chromatography tandem mass spectrometry at the University of California San Francisco (UCSF) using methods validated for urine [3,4].…”

Point-of-care urine tenofovir testing: making a good thing better

“…TAF has equal efficacy with lower toxicity than TDF with lower dose (10-25 mg vs. 245 mg) [7]. The two TAF doses are related to its use in different combinations, such as with LPV/r (10 mg) or with DTG (25 mg), but do not influence the urine elimination of TAF that is similar with both doses [8].…”