Pharmacokinetic interactions of modern antiretroviral therapy

Drug--drug interactions (DDIs) have been a clinical challenge in HIV medicine for over two decades. The newer antiretroviral drugs (ARTs) have significantly fewer DDIs than protease inhibitors and boosted integrase inhibitors (INSTIs). The lower propensity of such newer antiretrovirals (e.g. unboosted integrase inhibitors; doravirine) to cause DDIs, has been largely offset by the ageing cohort of patients with multiple comorbidities, who are taking multiple chronic medicines. Furthermore, the introduction of newly marketed drugs into clinical practice needs to be closely monitored, as the new drugs may be perpetrators of DDIs, leading to a potential change in the efficacy or toxicity of the coadministered antiretrovirals.