Morphine potentiates HIV infection and receptor expression in 3d brain organoids.

Opioid abuse is a major comorbidity of HIV, yet its direct effects on the brain remain unclear. Using iPSC-derived 3D human cerebral organoids (hCOs), we show that morphine directly upregulates HIV receptors CD4, CCR5, and CXCR4 in the absence of peripheral immune cells or a blood-brain barrier. This receptor induction drives a significant increase in HIV viral load within the CNS, revealing a brain-intrinsic mechanisms of opioid-mediated viral enhancement. These findings establish hCOs as a unique platform to investigate neuroHIV and provide critical insight into how opioids amplify CNS infection independently of peripheral factors.