HIV treatment simplification to elvitegravir/cobicistat/emtricitabine/tenofovir disproxil fumarate (E/C/F/TDF) plus darunavir: a pharmacokinetic study

AIDS Res Ther. 2017 Nov 2;14(1):59. doi: 10.1186/s12981-017-0185-4.

Abstract

Background: As a simplification strategy for treatment-experienced HIV-infected patients who have achieved virologic suppression on a multi-drug, multi-class antiretroviral regimen, the aim of this study was to evaluate the safety, efficacy, and pharmacokinetics of once-daily elvitegravir/cobicistat/emtricitabine/tenofovir disproxil fumarate (E/C/F/TDF) with darunavir.

Methods: A single arm, open-label 48-week study was conducted of regimen simplification to E/C/F/TDF plus darunavir 800 mg daily from stable therapy including two nucleoside/nucleotide reverse transcriptase inhibitors, a ritonavir-boosted protease inhibitor, and an integrase inhibitor. Participants had plasma HIV viral load consistently < 200 copies/mL for ≥ 6 months, estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, and no genotypic resistance to major components of the study regimen. Plasma viral load was measured at weeks 2 and 4, then every 4 weeks throughout the study. Safety laboratory assessments were conducted at baseline and at weeks 12, 24, 36, and 48. Antiretroviral drug concentrations were measured at baseline and once ≥ 2 weeks after the regimen change.

Results: Ten HIV-infected adults (8 male and 2 female; median age 50.5 years) were enrolled. All maintained virologic suppression on the new regimen for 48 weeks. One subject experienced a decrease in eGFR from 62 mL/min at baseline to 52 mL/min at week 12; study medications were continued and his eGFR remained stable (50-59 mL/min) thereafter. No subjects discontinued study medications for renal function changes or other adverse events. Darunavir trough concentration were lower on the new regimen than on darunavir/ritonavir 800/100 mg (n = 5; p < 0.05).

Conclusions: Despite low darunavir trough concentrations, treatment simplification to a two-pill, once-daily regimen of E/C/F/TDF plus darunavir was safe and effective for 48 weeks among 10 selected treatment-experienced HIV-infected patients. Trial registration The study protocol was registered with ClinicalTrials.gov (NCT02199613) on July 22, 2014.

Keywords: Antiretrovirals; Cobicistat; Darunavir; Elvitegravir; HIV.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / therapeutic use*
  • Cobicistat / adverse effects
  • Cobicistat / pharmacokinetics*
  • Cobicistat / therapeutic use
  • Darunavir / adverse effects
  • Darunavir / pharmacokinetics*
  • Darunavir / therapeutic use
  • Drug Therapy, Combination
  • Emtricitabine / adverse effects
  • Emtricitabine / pharmacokinetics*
  • Emtricitabine / therapeutic use
  • Female
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects
  • Humans
  • Integrase Inhibitors / adverse effects
  • Integrase Inhibitors / pharmacokinetics
  • Integrase Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Protease Inhibitors / adverse effects
  • Protease Inhibitors / pharmacokinetics
  • Protease Inhibitors / therapeutic use*
  • Quinolones / adverse effects
  • Quinolones / pharmacokinetics*
  • Quinolones / therapeutic use
  • Reverse Transcriptase Inhibitors / adverse effects
  • Reverse Transcriptase Inhibitors / pharmacokinetics
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Ritonavir / adverse effects
  • Ritonavir / pharmacokinetics*
  • Ritonavir / therapeutic use
  • Tenofovir / adverse effects
  • Tenofovir / pharmacokinetics*
  • Tenofovir / therapeutic use
  • Viral Load / drug effects

Substances

  • Anti-HIV Agents
  • Integrase Inhibitors
  • Protease Inhibitors
  • Quinolones
  • Reverse Transcriptase Inhibitors
  • elvitegravir
  • Tenofovir
  • Emtricitabine
  • Cobicistat
  • Ritonavir
  • Darunavir

Associated data

  • ClinicalTrials.gov/NCT02199613