Does HIV-1 infection drive Alzheimer's disease pathobiology?

Lifelong antiretroviral therapy extends the lifespan of individuals with human immunodeficiency virus (HIV). However, HIV-associated neurocognitive disorders (HAND) remain with age-linked comorbidities. Despite viral suppression, the co-development of Alzheimer's disease (AD) remains a concern. Both HAND and AD share key mechanisms, including chronic neuroinflammation, glial dysfunction, and progressive neurodegeneration. Microglial activation is a key contributor that generates persistent proinflammatory neurotoxins, promoting amyloid-β aggregation, disrupting clearance, and accelerating neurodegeneration. Persistent viral reservoirs and low-level viral protein expression disrupt glial homeostasis, enhancing oxidative stress, tau hyperphosphorylation, and synaptic damage in the brain. This review highlights the intersections between both disorders and discusses emerging rodent models to investigate convergent pathways with the goal of improving therapeutic strategies to preserve cognitive health.