Brief Report: Pharmacokinetics of Bictegravir and Tenofovir in Combination With Darunavir/Cobicistat in Treatment-Experienced Persons With HIV

J Acquir Immune Defic Syndr. 2021 Dec 1;88(4):389-392. doi: 10.1097/QAI.0000000000002765.

Abstract

Background: Bictegravir coformulated with emtricitabine and tenofovir alafenamide as a fixed-dose combination (BIC/FTC/TAF 50/200/25 mg) is recommended as an initial regimen in patients who are antiretroviral (ARV)-naïve or virologically suppressed on a stable ARV regimen. However, no real-world pharmacokinetic (PK) data are available in treatment-experienced patients with antiretroviral resistance receiving BIC/FTC/TAF plus a boosted protease inhibitor.

Setting/methods: This prospective, single-center, nonrandomized pharmacokinetic study enrolled adult treatment-experienced persons with HIV and creatinine clearance >30 mL/min receiving BIC/FTC/TAF + DRV/c as part of routine clinical care. Steady-state PK profiles of BIC, TAF, tenofovir (TFV), and DRV after daily dosing of BIC/FTC/TAF + darunavir/cobicistat (DRV/c) were obtained with samples at predose and 0.5, 1, 2, and 4 hours postdose. The AUC0-24 at steady state was extrapolated by imputing C0 for C24 for each participant (AUC0-tau,exp).

Results: Nine participants were enrolled with a median age of 59 years (range 54-67) and median number of years on ART of 19 (range 5.8-30). The median (interquartile range [IQR]) BIC AUC0-tau,exp and Cmax values were 128.9 µg*h/mL (78.1-159.5) and 6.9 µg/mL (5.1-9.8), respectively. The median (IQR) TAF AUC0-tau,exp and Cmax values were 0.376 µg*h/mL (0.199-0.430) and 0.276 µg/mL (0.149-0.543), respectively. Predose concentrations of TFV and DRV were comparable with historical data.

Conclusion: Treatment-experienced persons with HIV receiving BIC/FTC/TAF + darunavir/cobicistat (DRV/c) had BIC exposures (AUC0-tau) that were increased by approximately 26% compared with historical PK data. Although TAF exposures were substantially increased, plasma TFV was only modestly higher. These results suggest that BIC/TAF/FTC + DRV/c is a viable antiviral regimen option for treatment-experienced persons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amides / blood
  • Amides / pharmacokinetics*
  • Anti-HIV Agents / blood
  • Anti-HIV Agents / pharmacokinetics*
  • Antiretroviral Therapy, Highly Active / methods
  • Chromatography, Liquid
  • Cobicistat / blood
  • Cobicistat / pharmacokinetics*
  • Darunavir / blood
  • Darunavir / pharmacokinetics*
  • Female
  • HIV Infections / drug therapy*
  • Heterocyclic Compounds, 3-Ring / blood
  • Heterocyclic Compounds, 3-Ring / pharmacokinetics*
  • Humans
  • Male
  • Middle Aged
  • Piperazines / blood
  • Piperazines / pharmacokinetics*
  • Prospective Studies
  • Pyridones / blood
  • Pyridones / pharmacokinetics*
  • Tandem Mass Spectrometry
  • Tenofovir / blood
  • Tenofovir / pharmacokinetics*

Substances

  • Amides
  • Anti-HIV Agents
  • Heterocyclic Compounds, 3-Ring
  • Piperazines
  • Pyridones
  • bictegravir
  • Tenofovir
  • Cobicistat
  • Darunavir