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).

Autor:	Coyle RP; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Morrow M; Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Mann SC; Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Mainella V; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Ellis SL; Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Schwab S; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Coppinger C; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Barker N; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Ellison L; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Zheng JH; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Al Zuabi S; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Alpert PE; etectRx, Gainesville, Florida, USA., Carnes TC; etectRx, Gainesville, Florida, USA., Buffkin DE Jr; etectRx, Gainesville, Florida, USA., Chai PR; Department of Emergency Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.; Koch Institute for Integrated Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.; The Fenway Institute, Boston, Massachusetts, USA., Bushman LR; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Kiser JJ; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.; Medical Affairs, Merck & Co, Inc, Rahway, New Jersey, USA., MaWhinney S; Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Brooks KM; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Anderson PL; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA., Castillo-Mancilla JR; Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.; Clinical Development, ViiV Healthcare, Durham, North Carolina, USA.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2024 Nov 22; Vol. 79 (5), pp. 1233-1241.
DOI:	10.1093/cid/ciae212
Abstrakt:	Background: QUANTI-TAF aimed to establish tenofovir-diphosphate (TFV-DP)/emtricitabine-triphosphate (FTC-TP) adherence benchmarks in dried blood spots (DBS) for persons with human immunodeficiency virus (PWH) receiving tenofovir alafenamide/emtricitabine (TAF/FTC)-based antiretroviral therapy (ART). Methods: For 16 weeks, 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 TFV-DP and FTC-TP in DBS were quantified and summarized at steady-state (week 12 or 16) as median (interquartile range). Linear mixed-effects models evaluated factors associated with TFV-DP/FTC-TP. Results: Eighty-four participants (11% female, 4% transgender) predominantly receiving bictegravir/TAF/FTC (73%) were enrolled. Ninety-two percent completed week 12 or 16 (94% 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. Adjusting for cumulative adherence, TFV-DP was higher with boosted ART, lower body mass index, and in non-Black participants. 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% cumulative and 10-day adherence had TFV-DP ≥1800 fmol/punches and FTC-TP ≥2.5 pmol/punches, respectively. Low-level viremia (HIV-1 RNA 20-199 copies/mL) occurred at 18% of visits in 39% of participants with similar TFV-DP (3177 [2494-4149] fmol/punches) compared with suppressed visits (3279 [2580-4407] fmol/punches). Conclusions: TFV-DP ≥1800 fmol/punches and FTC-TP ≥2.5 pmol/punches represent DBS benchmarks for ≥85% adherence to unboosted TAF/FTC-based ART. Among PWH with high adherence, low-level viremia was common. Clinical Trials Registration: NCT04065347. Competing Interests: Potential conflicts of interest. J. R. C.-M. is an employee of ViiV Healthcare and has received research support from Gilead Sciences, paid to his institution. P. L. A. has received consulting fees from Gilead Sciences, Merck, and ViiV Healthcare and research support from Gilead Sciences, paid to his institution. K. M. B. has received consulting fees from ViiV Healthcare. J. J. K. is an employee of Merck. S. C. M. has received research support from Gilead Sciences, paid to her institution. P. E. A., T. C. C., and D. E. B. are employees of etectRx. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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