Polypharmacy in HIV: recent insights and future directions.

Purpose of Review: Update findings regarding polypharmacy among people with HIV (PWH) and consider what research is most needed.
Recent Findings: Among PWH, polypharmacy is common, occurs in middle age, and is predominantly driven by nonantiretroviral (ARV) medications. Many studies have demonstrated strong associations between polypharmacy and receipt of potentially inappropriate medications (PIMS), but few have considered actual adverse events. Falls, delirium, pneumonia, hospitalization, and mortality are associated with polypharmacy among PWH and risks remain after adjustment for severity of illness.
Summary: Polypharmacy is a growing problem and mechanisms of injury likely include potentially inappropriate medications, total drug burden, known pairwise drug interactions, higher level drug interactions, drug--gene interactions, and drug--substance use interactions (alcohol, extra-medical prescription medication, and drug use). Before we can effectively design interventions, we need to use observational data to gain a better understanding of the modifiable mechanisms of injury. As sicker individuals take more medications, analyses must account for severity of illness. As self-report of substance use may be inaccurate, direct biomarkers, such as phosphatidylethanol (PEth) for alcohol are needed. Large samples including electronic health records, genetics, accurate measures of substance use, and state of the art statistical and artificial intelligence techniques are needed to advance our understanding and inform clinical management of polypharmacy in PWH.