Table 1.
Key immune, viral, and pathology features of proposed biotypes of HIV-associated neurologic impairments.
| Biotype | Macrophage- mediated HIV encephalitis |
CNS viral escape | T cell-mediated HIV encephalitis |
HIV protein- associated encephalopathy |
|---|---|---|---|---|
| Clinical features | Subacute subcortical dementia | Headache, tremors, cognitive impairment, confusion, focal neurologic deficits, and seizures | Diverse symptoms. Can include sensory and visual changes, headache, confusion, cognitive impairment, seizures and coma | Slowly progressive cognitive and psychomotor impairments |
| ART status | Untreated. | Treated. Associated with low CNS drug penetration, poor drug compliance, and drug resistant viral mutations | Treated. | Treated. |
| Immune profile | CD4 T cells <200/mm3; elevated markers of macrophage activation in CSF | Asymptomatic: none; secondary and symptomatic: lymphocytic pleocytosis | Low CD4+ T cell nadir (<100 cells/μL) prior to ART, rapid immune restoration after initiation of ART; Lymphocytic pleocytosis(CD4+ or CD8+); microglial activation | Neuroinflammation, lymphocytic infiltration is possible. Microglial and astrocyte activation. |
| Viral profile | Viral load elevated in blood and CSF | Viral load elevated in CSF; ART resistant mutations | Often associated with opportunistic infections; HIV can be present in CSF or brain | Undetectable viral loads, but viral proteins (Tat, Nef, gp120, Vpr, and Gag) detectable in CSF |
| Pathology | Macrophage infiltration; multinucleated giant cells infected with HIV; astrocyte infection, neurodegeneration | Lymphocytic infiltrate into the CNS. | CD4+ or CD8+ immune infiltrate that can be both perivascular and diffuse into the parenchyma | Neuronal loss, Aβ and Tau deposits |
| Neuroimaging | Diffuse periventricular hyperintensities in white matter | White matter hyperintensities with deep brain nuclei involvement and enhancement | diffuse white matter hyperintensities with mild edema | Brain atrophy |
| Treatment | ART with CNS penetration | Changes to ART to enhance CNS penetration or overcome viral mutations. Treatment of secondary infection. | Treatment of opportunistic infection and corticosteroids. | None currently available. |
Aβ - Amyloid beta, ART – Antiretroviral therapy, CSF - Cerebrospinal fluid, CNS – Central nervous system