- HIV infection remains a major global health challenge due to its complex pathogenesis and lifelong persistence in people living with HIV (PLWH).
- A central barrier to eradication is the virus's ability to establish long-lived latent reservoirs in different tissues, including the central nervous system (CNS).
- In the CNS, HIV persists despite systemic viral suppression because of limited ART penetration across the blood-brain barrier (BBB).
- Modern ART regimens significantly reduce viral burden and HIV-related morbidity but do not eliminate neurocognitive complications.
- Suboptimal CNS drug penetration and certain ART-associated toxicities contribute to CNS dysfunction, persistent neuroinflammation, and accelerated aging of the brain.
- Prolonged exposure to ART and persistent low-level viral activity exacerbate chronic inflammation, immune activation, and metabolic dysregulation, collectively accelerating neurobiological aging.
- These pathological processes contribute to the development of HIV-associated neurocognitive disorders (HAND), which affect nearly half of virally suppressed PLWH.