Tenofovir-Diphosphate and Emtricitabine-Triphosphate Adherence Benchmarks in Dried Blood Spots for Persons with HIV Receiving Tenofovir Alafenamide and Emtricitabine-based Antiretroviral Therapy (QUANTI-TAF)

Ryan P Coyle; Mary Morrow; Sarah C Mann; Vincent Mainella; Samuel L Ellis; Stefanie Schwab; Corwin Coppinger; Nicholas Barker; Lucas Ellison; Jia-Hua Zheng; Subhi Al Zuabi; Pamela E Alpert; Tony C Carnes; D Eric Buffkin Jr; Peter R Chai; Lane R Bushman; Jennifer J Kiser; Samantha MaWhinney; Kristina M Brooks; Peter L Anderson; Jose R Castillo-Mancilla

doi:10.1093/cid/ciae212

Tenofovir-Diphosphate and Emtricitabine-Triphosphate Adherence Benchmarks in Dried Blood Spots for Persons with HIV Receiving Tenofovir Alafenamide and Emtricitabine-based Antiretroviral Therapy (QUANTI-TAF)

Clin Infect Dis. 2024 Apr 18:ciae212. doi: 10.1093/cid/ciae212. Online ahead of print.

Authors

Ryan P Coyle¹, Mary Morrow², Sarah C Mann³, Vincent Mainella¹, Samuel L Ellis⁴, Stefanie Schwab¹, Corwin Coppinger¹, Nicholas Barker¹, Lucas Ellison¹, Jia-Hua Zheng¹, Subhi Al Zuabi¹, Pamela E Alpert⁵, Tony C Carnes⁵, D Eric Buffkin Jr⁵, Peter R Chai^{6

7

8}, Lane R Bushman¹, Jennifer J Kiser^{1

9}, Samantha MaWhinney², Kristina M Brooks¹, Peter L Anderson¹, Jose R Castillo-Mancilla^{3

10}

Affiliations

¹ Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
² Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
³ Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁴ Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁵ etectRx, Gainesville, FL, USA.
⁶ Department of Emergency Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁷ Koch Institute for Integrated Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁸ The Fenway Institute, Boston, MA, USA.
⁹ Merck & Co., Inc., Rahway, NJ, USA.
¹⁰ ViiV Healthcare, Durham, NC, USA.

PMID: 38636950
DOI: 10.1093/cid/ciae212

Abstract

Background: QUANTI-TAF aimed to establish tenofovir-diphosphate/emtricitabine-triphosphate (TFV-DP/FTC-TP) adherence benchmarks in dried blood spots (DBS) for persons with HIV (PWH) receiving tenofovir alafenamide/emtricitabine (TAF/FTC)-based antiretroviral therapy (ART).

Methods: During a 16-week pharmacokinetic study, PWH received TAF/FTC-based ART co-encapsulated with an ingestible sensor to directly measure cumulative (enrollment to final visit) and 10-day adherence. At monthly visits, intraerythrocytic concentrations of TAF/FTC anabolites (TFV-DP/FTC-TP) in DBS were quantified by LC-MS/MS and summarized at steady-state (week 12 or 16) as median (IQR). Linear mixed-effects models evaluated factors associated with TFV-DP/FTC-TP.

Results: 84 participants (86% male, 11% female, and 4% transgender), predominantly receiving bictegravir/TAF/FTC (73%) enrolled. 92% completed week 12 or 16 (94% receiving unboosted ART). TFV-DP for <85% (7/72), ≥85%-<95% (9/72), and ≥95% (56/72) cumulative adherence was 2696 (2039-4108), 3117 (2332-3339), and 3344 (2605-4293) fmol/punches. All participants with ≥85% cumulative adherence had TFV-DP ≥1800 fmol/punches. Adjusting for cumulative adherence, TFV-DP was higher with boosted ART, lower BMI, and in non-Blacks. FTC-TP for <85% (14/77), ≥85%-<95% (6/77), and ≥95% (57/77) 10-day adherence was 3.52 (2.64-4.48), 4.58 (4.39-5.06), and 4.96 (4.21-6.26) pmol/punches. All participants with ≥85% 10-day adherence had FTC-TP ≥2.5 pmol/punches. Low-level viremia (HIV-1 RNA ≥20-<200 copies/mL) occurred at 60/335 (18%) visits in 33/84 (39%) participants (range: 20-149 copies/mL), with similar TFV-DP (3177 [2494-4149] fmol/punches) compared with HIV-1 RNA <20 copies/mL visits (3279 [2580-4407] fmol/punches).

Conclusions: We propose PK-based TFV-DP (≥1800 fmol/punches)/FTC-TP (≥2.5 pmol/punches) benchmarks in DBS for PWH receiving unboosted TAF/FTC-based ART with ≥85% adherence. In the setting of high adherence, low-level viremia was common.

Keywords: adherence benchmarks; dried blood spots; low-level viremia; tenofovir alafenamide; tenofovir-diphosphate.

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