title: Occurrence of selective ritonavir nonadherence and dose-staggering in recipients of boosted HIV-1 protease inhibitor therapy.
abstract: BACKGROUND
  The inhibitory effect of ritonavir on hepatic cytochrome P450 enzymes is a critical factor in achieving optimal levels of co-administered "boosted" protease inhibitors (PIs). Even though nonadherence to antiretroviral medications is a common phenomenon, the prevalence of selective ritonavir nonadherence and dosestaggering (i.e., separating ritonavir and boosted PI doses in time) are unknown.
  
  
  METHODS
  HIV-1-infected adults receiving a regimen containing ritonavir-boosted atazanavir or fosamprenavir were recruited into a prospective study of adherence and dosage timing of both agents. These parameters were measured over 24 weeks using the Medication Event Monitoring System (MEMS; Aardex, Union, California, USA). A subject was deemed to be selectively nonadherent to ritonavir if his/her adherence rate to the boosted PI exceeded that of ritonavir by >5%. Dose-staggering was defined as a temporal separation of boosted PI from its corresponding ritonavir dose of >4 hours but <12 hours.
  
  
  RESULTS
  The final study population consisted of 36 subjects. Three subjects (8.3%) were selectively nonadherent to ritonavir, 17 (47.2%) staggered any doses of ritonavir, and 3 (8.3%) staggered more than 5% of their ritonavir doses. Two of these three were also selectively nonadherent to ritonavir. There was no evident impact of these behaviors on HIV viral load (VL); all subjects who were selectively nonadherent to or frequently staggered doses of ritonavir had VL <75 copies/mL at 24 weeks.
  
  
  CONCLUSIONS
  Selective ritonavir nonadherence and dose-staggering occurs in a small but significant minority of boosted PI recipients.
authors.affiliation: AIDS Center and Division of Infectious Diseases, Montefiore Medical Center, Bronx, New York, USA Albert Einstein College of Medicine, Bronx, New York, USA. jshuter@montefiore.org
authors.forename: Jonathan
authors.initials: J
authors.lastname: Shuter
authors.forename: Julie A
authors.initials: JA
authors.lastname: Sarlo
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rode
authors.forename: Barry S
authors.initials: BS
authors.lastname: Zingman
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D002219:Carbamates / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy* / Q000523:psychology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D008297:Male; D008491:Medical Informatics Applications; D008875:Middle Aged; D009519:New York City; D009842:Oligopeptides / Q000627:therapeutic use; D010755:Organophosphates / Q000627:therapeutic use; D011446:Prospective Studies; D011725:Pyridines / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use; D011795:Surveys and Questionnaires; D019562:Viral Load; D016903:Drug Monitoring
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D010755:Organophosphates; D011725:Pyridines; D013449:Sulfonamides; D000069446:Atazanavir Sulfate; D019438:Ritonavir; C426859:fosamprenavir