title: Pharmacokinetics and pharmacodynamics of boosted once-daily darunavir.
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.
authors.affiliation: Janssen Research & Development, LLC, Titusville, NJ, USA tkakuda@its.jnj.com.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Kakuda
authors.affiliation: Janssen Research and Development, BV, Beerse, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Brochot
authors.affiliation: Janssen Research & Development, LLC, Titusville, NJ, USA.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Tomaka
authors.affiliation: Janssen Research and Development, BV, Beerse, Belgium.
authors.forename: Tony
authors.initials: T
authors.lastname: Vangeneugden
authors.affiliation: Janssen Research and Development, BV, Beerse, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Van De Casteele
authors.affiliation: Janssen Research and Development, BV, Beerse, Belgium.
authors.forename: Richard M W
authors.initials: RM
authors.lastname: Hoetelmans
mesh_terms: D000367:Age Factors; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000069454:Darunavir; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D015497:HIV-1; D006801:Humans; D008297:Male; D011247:Pregnancy; D012737:Sex Factors; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D000069454:Darunavir
keywords: HIV protease inhibitors; antiretroviral; pharmacology