Prevalence of drug-drug interactions in the era of HIV integrase inhibitors: a retrospective clinical study

Background: Antiretroviral agents pose a high risk for drug-drug interactions (DDIs), mainly but not limited to being a substrate, inducer or inhibitor of P450 cytochrome enzymes. In part metabolised by other pathways, integrase inhibitors might show a more favourable profile. The aim of this study was to investigate the prevalence of DDIs in daily clinical practice for patients starting different antiretroviral treatment (ART) regimens. Methods: All patients starting ART in our centre from January 2009 to April 2016 were included. All prescribed co-medications since the start of ART were recorded retrospectively from the medical files and screened for DDIs using the Liverpool HIV drug interaction database. Only DDIs between antiretroviral and non-antiretroviral drugs were considered. Results: We included 145 patients, of which 42% were on an integrase inhibitor-based regimen, mainly dolutegravir and elvitegravir. Of the patients, 78% (n = 113) took co-medication. Potential DDIs were seen in 63% of the patients with co-medication; contraindicated prescriptions were detected in 1%. Protease inhibitor-based ART was a risk factor for DDI (odds ratio (OR) 2.57; 95% confidence interval (CI) 1.06-6.19), in contrast to non-nucleoside reverse transcriptase inhibitor-based ART (OR 0.77; 95% CI 0.32-1.84). Concerning integrase inhibitors, a significantly lower risk was seen with dolutegravir-based treatment (OR 0.35; 95% CI 0.15-0.82), though not for elvitegravir-based ART (OR 2.51; 95% CI 0.66-9.58). Conclusions: ART regimens pose a dissimilar risk for drug-drug interactions in clinical practice. Regarding the use of integrase inhibitors, a significantly lower risk was seen with dolutegravir-based treatment.