[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Central nervous system](https://durgical.com/en/general-pathology/areas/cns/) › HIV in the brain and PML

# 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.

Updated Nov 12, 2026

## Key points

- HIV infects microglia and macrophages; the hallmark is microglial nodules with multinucleated giant cells.
- HIV-associated neurocognitive disorder: from mild impairment to dementia; less severe in the era of antiretroviral therapy.
- Vacuolar myelopathy: vacuolated dorsal and lateral columns, resembling B12 deficiency.
- PML: JC virus in oligodendrocytes; patchy demyelination, enlarged oligodendrocyte nuclei with glassy inclusions, bizarre giant astrocytes.
- IRIS: immune reconstitution inflammatory syndrome, a worsening when treatment restores CD4 cells and they attack residual antigens.
- Other CNS problems in AIDS: toxoplasmosis, cryptococcal meningitis, CMV, primary CNS lymphoma (EBV).

## 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](https://durgical.com/en/conditions/hiv-infection-and-aids/) | 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](https://durgical.com/en/conditions/toxoplasmosis/) | Toxoplasma gondii | Multiple ring-enhancing lesions in basal ganglia and grey-white junction |
| [Primary CNS lymphoma](https://durgical.com/en/conditions/primary-central-nervous-system-lymphoma/) | EBV-driven B cells | Periventricular enhancing mass, EBV DNA in CSF |
| [Cryptococcal meningitis](https://durgical.com/en/conditions/cryptococcal-meningitis/) | Cryptococcus neoformans | High opening pressure, positive antigen |
| [CMV ventriculoencephalitis](https://durgical.com/en/conditions/cytomegalovirus-infection/) | 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.

## Memory aid

HIV makes giant cells in the microglia; JC eats the myelin makers when the guards (CD4) are gone.

## 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.

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## Elsewhere in DurgiPedia

- [How HIV destroys CD4 T cells](https://durgical.com/en/immunology/how-hiv-destroys-cd4-t-cells/)
- [Secondary immunodeficiency: HIV, malnutrition, drugs, asplenia](https://durgical.com/en/immunology/secondary-immunodeficiency-hiv-malnutrition-drugs-asplenia/)

## Connections

## Related 5

- [Primary CNS lymphoma](https://durgical.com/en/general-pathology/primary-cns-lymphoma/)
- [Parasitic brain infections](https://durgical.com/en/general-pathology/parasitic-brain-infections/)
- [Fungal infections of the CNS](https://durgical.com/en/general-pathology/fungal-infections-of-the-cns/)
- [Herpesvirus encephalitis](https://durgical.com/en/general-pathology/herpesvirus-encephalitis/)
- [Viral encephalitis: the shared pattern](https://durgical.com/en/general-pathology/viral-encephalitis-the-shared-pattern/)

## Related conditions 6

- [HIV infection and AIDS](https://durgical.com/en/conditions/hiv-infection-and-aids/)
- [Primary central nervous system lymphoma](https://durgical.com/en/conditions/primary-central-nervous-system-lymphoma/)
- [Toxoplasmosis](https://durgical.com/en/conditions/toxoplasmosis/)
- [Cryptococcal meningitis](https://durgical.com/en/conditions/cryptococcal-meningitis/)
- [Cytomegalovirus infection](https://durgical.com/en/conditions/cytomegalovirus-infection/)
- [Dementia (major neurocognitive disorder)](https://durgical.com/en/conditions/dementia/)

## Microorganisms 2

- [Human immunodeficiency virus](https://durgical.com/en/microbiology/human-immunodeficiency-virus/)
- [JC polyomavirus](https://durgical.com/en/microbiology/jc-polyomavirus/)

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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](https://medlineplus.gov/ency/article/000674.htm) (MedlinePlus, US National Library of Medicine, 2026).

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Representative model, for educational purposes only.

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