Steady-State Amprenavir, Tenofovir, and Emtricitabine Pharmacokinetics Before and After Reducing Ritonavir Boosting of a Fosamprenavir/Tenofovir/Emtricitabine Regimen from 200 mg to 100 mg Once Daily (TELEX II)

Abstract

Purpose: Evaluate how reducing ritonavir (RTV) boosting from 200 mg to 100 mg once daily (QD) affects steady-state pharmacokinetics of components of a fosamprenavir (FPV)-based regimen. Methods: Prospective, open-label, pharmacokinetic study in 12 HIV-infected patients stabilized on FPV/RTV 1400 mg/200 mg + tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) 300 mg/200 mg QD (TELEX II). Pharmacokinetics were assessed by noncompartmental analysis at baseline and 4 weeks after RTV reduction to 100 mg QD. Results: Baseline median minimum plasma concentration (C_min) and area under the plasma concentration-time curve over 24 hours post dose (AUC_24h) were as follows: APV: 1,708 ng/mL, 84,260 h • ng/mL; tenofovir: 53 ng/mL, 2,420 h • ng/mL; FTC: 58 ng/mL, 9,190 h • ng/mL; RTV: 80 ng/mL, 10,230 h • ng/mL. Four weeks after reducing RTV, changes in C_min and AUC_24h were: APV: +26%, +0.6%; tenofovir: +77%, +30%; FTC: +188%, +13%; RTV –64%, –79%. Component plasma concentration ranges were consistent with historical values. Median APV C_min was 14.7-fold above the protein-binding-adjusted 50% inhibitory concentration of wild-type HIV. Four weeks after RTV reduction, HIV-1 RNA levels remained <50 copies/mL in all patients, median CD4+ count increased from 465 to 495 cells/mm³, and favorable lipid changes and no adverse events were observed. Conclusion: Reducing RTV boosting from 200 to 100 mg QD of FPV/TDF/FTC QD conferred no detrimental effect on APV, tenofovir, FTC, or RTV pharmacokinetics and maintained virologic suppression.

Keywords:

• emtricitabine
• HIV infection
• fosamprenavir
• ritonavir
• tenofovir disoproxil fumarate