HIV in the brain and PML
- Lesion
HIV can damage the brain directly and opens the door to infections such as JC virus, which destroys the cells that make myelin.
What it is
HIV enters the brain early in infection, carried by monocytes, and infects microglia and macrophages rather than neurons. Without treatment it causes a meningoencephalitis with multinucleated giant cells and HIV-associated neurocognitive disorder. Immunosuppression adds opportunistic infections (toxoplasmosis, cryptococcus, CMV) and lymphoma. JC polyomavirus reactivates in severe immune deficiency and infects oligodendrocytes, causing progressive multifocal leukoencephalopathy (PML). Restoring immunity with treatment can paradoxically worsen inflammation (IRIS).
Structure
- HIV encephalitis: microglial nodules, multinucleated giant cells, white matter pallor and gliosis, mainly in subcortical white matter and deep grey matter.
- PML gross: patchy, often confluent areas of destroyed white matter, usually in the cerebral hemispheres.
- PML micro: loss of myelin, lipid-laden macrophages, infected oligodendrocytes with ground-glass nuclear inclusions at the edges.
Step by step
- HIV enters the brain inside monocytes that become perivascular macrophages.
- Infected macrophages and microglia release viral proteins and cytokines toxic to neurons.
- Synapses and neurons are lost, causing cognitive decline.
- As CD4 cells fall, latent JC virus reactivates and infects oligodendrocytes.
- Oligodendrocytes die and myelin is lost in expanding patches (PML).
Brain lesions in advanced HIV
| Lesion | Cause | Clue |
|---|---|---|
| HIV encephalitis | HIV in microglia and macrophages | Microglial nodules with multinucleated giant cells |
| Progressive multifocal leukoencephalopathy | JC virus | Non-enhancing white matter lesions, no mass effect |
| Toxoplasmosis | Toxoplasma gondii | Multiple ring-enhancing lesions in basal ganglia and grey-white junction |
| Primary CNS lymphoma | EBV-driven B cells | Periventricular enhancing mass, EBV DNA in CSF |
| Cryptococcal meningitis | Cryptococcus neoformans | High opening pressure, positive antigen |
| CMV ventriculoencephalitis | Cytomegalovirus | Periventricular enhancement, retinitis |
Clinical notes
- PML presents with progressive focal deficits, visual loss and cognitive change; it also occurs with some immunomodulating drugs.
- HIV remains a major health problem in Latin America; early treatment prevents most of these complications.
Test yourself
Think of the answer, then tap the question to see it.
Which CNS cells does HIV mainly infect?
Microglia and perivascular macrophages, not neurons.
What are the histologic features of PML?
Patchy demyelination, oligodendrocytes with enlarged glassy nuclear inclusions, bizarre reactive astrocytes and lipid-laden macrophages.
What is IRIS?
Immune reconstitution inflammatory syndrome: inflammatory worsening of an infection after antiretroviral therapy restores immune function.
Elsewhere in DurgiPedia
Connections
Microorganisms2
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Progressive multifocal leukoencephalopathy: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.