Interactions between long-acting antiretrovirals and opioids: a call for clinical awareness

SUMMARYThis review summarizes potential drug-drug interactions (DDIs) between long-acting antiretrovirals (LAAs) and opioids, focusing on pharmacodynamics (PD), pharmacokinetics (PK), and side effects related to absorption, distribution, metabolism, and excretion (ADME). It also covers dysregulation in epigenetics and in the immune system. A comprehensive literature review was performed using PubMed and Google Scholar, along with data from the Liverpool HIV Drug Interactions Database, to evaluate pharmacokinetic interactions between LAA drugs, such as cabotegravir, rilpivirine, lenacapavir, and dapivirine, with opioids used in clinical settings, including morphine, tramadol, oxycodone, and codeine; medications for opioid use disorder (MOUD), such as methadone and buprenorphine; and the illicit opioids, including fentanyl and heroin. The review highlights key factors increasing DDI risk and discusses clinical considerations for managing preexposure prophylaxis (PrEP) or antiretroviral therapy (ART) in persons who use opioids. Lastly, it proposes research strategies for studying DDIs, including the use of animal models, physiologically based pharmacokinetic (PBPK) models, and clinical trials.