Pharmacokinetics and pharmacodynamics of boosted once-daily darunavir

J Antimicrob Chemother. 2014 Oct;69(10):2591-605. doi: 10.1093/jac/dku193. Epub 2014 Jun 20.

Abstract

The ability to dose antiretroviral agents once daily simplifies the often complex therapeutic regimens required for the successful treatment of HIV infection. Thus, once-daily dosing can lead to improved patient adherence to medication and, consequently, sustained virological suppression and reduction in the risk of emergence of drug resistance. Several trials have evaluated once-daily darunavir/ritonavir in combination with other antiretrovirals (ARTEMIS and ODIN trials) or as monotherapy (MONET, MONOI and PROTEA trials) in HIV-1-infected adults. Data from ARTEMIS and ODIN demonstrate non-inferiority of once-daily darunavir/ritonavir against a comparator and, together with pharmacokinetic data, have established the suitability of once-daily darunavir/ritonavir for treatment-naive and treatment-experienced patients with no darunavir resistance-associated mutations. The findings of ARTEMIS and ODIN have led to recent updates to treatment guidelines, whereby once-daily darunavir/ritonavir, given with other antiretrovirals, is now a preferred treatment option for antiretroviral-naive adult patients and a simplified treatment option for antiretroviral-experienced adults who have no darunavir resistance-associated mutations. Once-daily dosing with darunavir/ritonavir is an option for treatment-naive and for treatment-experienced paediatric patients with no darunavir resistance-associated mutations based on the findings of the DIONE trial and ARIEL substudy. This article reviews the pharmacokinetics, efficacy, safety and tolerability of once-daily boosted darunavir. The feasibility of darunavir/ritonavir monotherapy as a treatment approach for some patients is also discussed. Finally, data on a fixed-dose combination of 800/150 mg of darunavir/cobicistat once daily are presented, showing comparable darunavir bioavailability to that obtained with 800/100 mg of darunavir/ritonavir once daily.

Keywords: HIV protease inhibitors; antiretroviral; pharmacology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age Factors
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / pharmacokinetics
  • Darunavir
  • Drug Interactions
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Protease Inhibitors / administration & dosage*
  • HIV Protease Inhibitors / adverse effects
  • HIV Protease Inhibitors / pharmacokinetics*
  • HIV-1
  • Humans
  • Male
  • Pregnancy
  • Sex Factors
  • Sulfonamides / administration & dosage*
  • Sulfonamides / adverse effects
  • Sulfonamides / pharmacokinetics*

Substances

  • Anti-HIV Agents
  • HIV Protease Inhibitors
  • Sulfonamides
  • Darunavir