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 Nov 22;79(5):1233-1241. doi: 10.1093/cid/ciae212.

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.

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

Publication types

  • Observational Study

MeSH terms

  • Adenine* / administration & dosage
  • Adenine* / analogs & derivatives
  • Adenine* / pharmacokinetics
  • Adenine* / therapeutic use
  • Adult
  • Alanine / administration & dosage
  • Alanine / analogs & derivatives
  • Alanine / pharmacokinetics
  • Alanine / therapeutic use
  • Anti-HIV Agents* / administration & dosage
  • Anti-HIV Agents* / pharmacokinetics
  • Anti-HIV Agents* / therapeutic use
  • Assessment of Medication Adherence*
  • Benchmarking
  • Dried Blood Spot Testing* / methods
  • Emtricitabine* / administration & dosage
  • Emtricitabine* / pharmacokinetics
  • Emtricitabine* / therapeutic use
  • Female
  • HIV Infections* / drug therapy
  • Humans
  • Male
  • Middle Aged
  • Organophosphates / administration & dosage
  • Organophosphates / blood
  • Organophosphates / pharmacokinetics
  • Organophosphates / therapeutic use

Substances

  • Adenine
  • Alanine
  • Anti-HIV Agents
  • Emtricitabine
  • Organophosphates
  • tenofovir alafenamide
  • tenofovir diphosphate

Associated data

  • ClinicalTrials.gov/NCT04065347