Evolving patterns of antiretroviral drug interactions in people with HIV in British Columbia, Canada

Abstract

Objectives: To characterize the annual prevalence of antiretroviral/nonantiretroviral drug interactions in relation to antiretroviral therapy (ART)-prescribing patterns, and to describe drug interaction-related ART changes.Design/methods: This cohort study included ART-treated adults in British Columbia, Canada between 01 January 2010 and 31 December 2016. Medication dispensing records were abstracted from a population-based, linked administrative-health dataset and used to identify antiretroviral-comedication drug interactions ('caution'/'avoid' drug interactions in HIV-focused drug interaction checkers). We identified temporal trends in annual drug interaction prevalence and quantified the association between taking higher drug interaction-risk ART and receiving nonrecommended antiretroviralcomedication combinations using Poisson regression models, modified for binary outcomes and correlated data. Clinician-reported, drug interaction-related ART changes and associated adverse events were abstracted from an HIV drug treatment registry and summarized descriptively.Results: Among 8571 ART-treated adults who received nonantiretroviral comedications, prevalence of having any drug interaction or receiving nonrecommended drug combination(s) significantly declined from 85 to 71% and 5.6 to 3.2%, respectively, between 2010 and 2016 (P < 0.001). This paralleled a shift from higher drug interactionrisk ART (e.g. ritonavir/cobicistat-boosted protease inhibitors) to lower drug interactionrisk ART (e.g. unboosted integrase inhibitors). Risk of receiving a nonrecommended antiretroviral-comedication combination was greater for persons taking higher vs. lower drug interaction-risk ART [adjusted risk ratio (aRR) 3.12, 95% confidence interval (CI) 2. 24-4.35]. Boosted antiretroviral-inhaled corticosteroid drug interactions accounted for the most commonly dispensed, nonrecommended drug combinations, and the most commonly reported drug interaction-related adverse events (adrenal insufficiency). Conclusion:The prevalence of antiretroviral-comedication drug interactions is declining as ART shifts towards antiretrovirals with lower drug interaction potential but nonrecommended drug combinations remain a concern. Healthcare providers should screen for drug interactions whenever drugs are prescribed or dispensed.

Prevalence of Potentially Clinically Significant Drug–Drug Interactions With Antiretrovirals Against HIV Over Three Decades: A Systematic Review of the Literature

“…The authors found that numbers of both amber and red DDIs fell over the years studied, an effect they attributed to the move away from boosted protease inhibitor regimens to unboosted integrase inhibitors. 24 This single-center evaluation provides granular evidence that uptake of modern, integrase-containing regimens is associated with a reduction in clinically significant DDIs, whereas studies like ours, while offering broader global representation, are unavoidably heterogenous with less ability to examine the isolated effect of integrase inhibitor use.…”

Cardiovascular Dynamics in HIV: The Influence of Adrenal Function and Nutritional Status

“…32,[35][36][37][38][39][40] After the discontinuation of the offending corticosteroid, secondary adrenal insufficiency marked by low levels of adrenocorticotropic hormone (ACTH) can then occur. 31,38,39,[41][42][43][44][45] In a retrospective chart review, 11% of PLHIV who were taking a protease inhibitor when they received a steroid injection developed an abnormality of adrenal function. 46 Tertiary adrenal insufficiency results from the deficiency of corticotropin-releasing hormone.…”