Integrase inhibitors and reduction in prevalence of potential drug-drug interactions

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The introduction of integrase inhibitors has been accompanied by a reduction in the prevalence of potential drug-drug interactions among people with HIV taking antiretrovirals in Switzerland, investigators report. Nevertheless, potential interactions were still observed for 29% of individuals, a finding that the investigators attribute to the ageing of people living with HIV and the resulting increasing need to use medications to treat other health conditions, such as cardiovascular disease and depression. Potentially dangerous, or ‘red flag’ interactions, were present for 2% of people, exactly the same proportion as over a decade ago.

In 2008, an analysis of people enrolled in the Swiss HIV Cohort Study found that 40% had potential drug-drug interactions. There have been major developments in HIV treatment since then, especially the introduction of integrase inhibitors and second-generation NNRTIs. These have a much lower risk of drug-drug interactions than older antiretrovirals – boosted protease inhibitors and older NNRTIs – because of the way they are processed by the body.

Dr Elisabeth Deutschmann of the University of Basel and her co-investigators therefore decided to repeat the 2008 study and see what proportion of people in the Swiss HIV Cohort in 2018 had potential drug-drug interactions. The investigators also wanted to determine the factors associated with the presence of potential interactions.

When considering the changes between 2008 and 2018, it’s important to bear in mind that the study population was older in 2018 than 2008 (median = 51 vs 46 years). Indeed, older age was a significant risk factor for the presence of a potential red or amber flag interaction in 2018 (per additional ten years, aOR = 1.10; 95% CI, 1.0-1.2).

There was a reduction between 2008 and 2018 in the proportion taking boosted antiretrovirals (a 24% fall) and NNRTIs (down by 13%). This is consistent with the development of HIV treatment guidelines which have prioritised integrase inhibitors and other newer, potent and safer therapies.

Patterns of co-medication use were broadly similar in 2008 and 2018 with cardiovascular drugs the most common. The prevalence of potential drug-drug interactions related to use of erectile dysfunction treatments increased from 3% in 2008 to 10% in 2018, possibly due to the ageing of the study population.

Background: 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.
Methods: 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).
Results: 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 > 1 comedication, 14% had polypharmacy (> 5 comedications) and 29% had > 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.
Conclusions: 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.

Elisabeth Deutschmann, Heiner C Bucher, Steffen Jaeckel, Sara Gibbons, Katie McAllister, Alexandra U Scherrer, Dominique L Braun, Matthias Cavassini, Anna Hachfeld, Alexandra Calmy, Manuel Battegay, Michela Cipriani, Luigia Elzi, James Young, Beatriz Lopez-Centeno, Juan Berenguer, Saye Khoo, Giusi Moffa, Catia Marzolini, Swiss HIV Cohort Study


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