Prevalence of Potential Drug–Drug Interactions in Patients of the Swiss HIV Cohort Study in the Era of HIV Integrase Inhibitors

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Prevalence of potential drug-drug interactions (PDDIs) between antiretroviral drugs (ARVs) and comedications was high in 2008 in a Swiss HIV Cohort Study (SHCS) survey. We reassessed the prevalence of PDDIs in the era of HIV integrase inhibitors (INIs), characterized by more favorable interaction profiles.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>The prevalence of PDDIs in treated HIV positive individuals was assessed for the period: 01-12/2018 by linkage of the Liverpool HIV drug interactions and SHCS databases. PDDIs were categorized as harmful (red flagged), of potential clinical relevance (amber flagged) or of weak clinical significance (yellow flagged).</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In 9’298 included individuals, median age was 51 years (IQR 43; 58), and 72% were males. Individuals received unboosted INIs (40%), boosted ARVs (30%), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) (32%) based regimens. In the entire cohort, 68% received &amp;gt; 1 comedication, 14% had polypharmacy (&amp;gt; 5 comedications) and 29% had &amp;gt; 1 PDDI. Among individuals with comedication, the prevalence of combined amber and yellow PDDIs was 43% (33% amber - mostly with cardiovascular drugs - and 20% yellow flagged PDDIs) compared to 59% in 2008. Two percent had red flagged PDDIs (mostly with corticosteroids), the same as in the 2008 survey. Compared to 2008, fewer individuals received boosted ARVs (-24%) and NNRTIs (-13%) but the use of comedications was higher.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Prevalence of PDDIs was lower with more widespread use of INIs in 2018 than in 2008. Continued use of boosted regimens and increasing needs for comedications in this aging population impeded lower rates of PDDIs.</jats:p> </jats:sec>

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

“…In contrast to two other studies, which observed stable prevalence of nonrecommended drug combinations in two measurement periods 4 or 10 years apart [7,20], we observed a statistically significant, downward trend in nonrecommended drug combinations, falling from 5.6 to 3.2% between 2010 and 2016. Our findings were consistent with the 1-5.5% prevalence of nonrecommended antiretroviral-comedications reported by others [6][7][8]19,20,38]. Similar to observations in Europe and Australia, the most common, nonrecommended antiretroviral-comedication combinations in BC included boosted antiretrovirals with inhaled corticosteroids and antiplatelet/anticoagulant drugs, and atazanavir or rilpivirine with PPIs [6][7][8][9]19,20,38].…”

“…The high prevalence of boosted protease inhibitor regimen use in BC (47% in 2016) may also have increased observed drug interaction prevalence. The modest, 14% reduction in overall drug interaction prevalence in BC from 2010 to 2016 was similar to the 16% reduction in observed in the Swiss Cohort between 2008 and 2018 [7,37].…”

Medication burden and clustering in people living with HIV undergoing therapeutic drug monitoring

“…Additionally using more drugs may expose patients to drug‐to‐drug interactions (DDIs) with potentially serious health hazards 5 . While DDIs seem less common with modern ARVs, there are some manageable but unavoidable interactions and some patients require boosting agents; the latter have been associated with a higher risk of DDI due to cytochromes and transporters inhibition 6 …”

“…5 While DDIs seem less common with modern ARVs, there are some manageable but unavoidable interactions and some patients require boosting agents; the latter have been associated with a higher risk of DDI due to cytochromes and transporters inhibition. 6 While the clustering of comorbidities has already been studied, little is known about how co-medications cluster in PLWH and controls. 7 This issue may be useful for identifying patients at risk of multiple DDIs and for selecting subgroups having a larger benefit from deprescription of concomitant medications.…”

Severe hyperkalaemia due to a potential drug–drug interaction between eplerenone and antiretrovirals in a HIV-positive patient after a myocardial infarction

“…8 Dolutegravir, which was included in the second antiretroviral regimen of the patient, has a favourable DDI profile because it does not significantly induce or inhibit the cytochrome P450 or glucuronidation systems. 9 For that reason, no DDIs were expected after eplerenone re-initiation.…”