Occurrence of selective ritonavir nonadherence and dose-staggering in recipients of boosted HIV-1 protease inhibitor therapy

Jonathan Shuter, Julie A. Sarlo, Richard A. Rode, Barry S. Zingman

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)135-142
Number of pages8
JournalHIV Clinical Trials
Volume10
Issue number3
DOIs
StatePublished - Jan 1 2009

Fingerprint

HIV Protease Inhibitors
Ritonavir
Protease Inhibitors
Therapeutics
Viral Load
Human immunodeficiency virus 1 p16 protease
Cytochrome P-450 Enzyme System
Micro-Electrical-Mechanical Systems

Keywords

  • Adherence
  • Dose-staggering
  • HIV
  • MEMS
  • Ritonavir
  • Selective

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Occurrence of selective ritonavir nonadherence and dose-staggering in recipients of boosted HIV-1 protease inhibitor therapy. / Shuter, Jonathan; Sarlo, Julie A.; Rode, Richard A.; Zingman, Barry S.

In: HIV Clinical Trials, Vol. 10, No. 3, 01.01.2009, p. 135-142.

Research output: Contribution to journalArticle

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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.",
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