Tenofovir-Diphosphate and Emtricitabine-Triphosphate Adherence Benchmarks in Dried Blood Spots for Persons With Human Immunodeficiency Virus Receiving Tenofovir Alafenamide and Emtricitabine–Based Antiretroviral Therapy (QUANTI-TAF)

Abstract

Abstract 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.