A 58-year-old man with longstanding HIV presented with a five-month history of progressive cognitive dysfunction and gait instability. He was adherent to Highly Active Anti-Retroviral Therapy (HAART). CD4 count three months before the onset of symptoms had been 560 cells/µL with an undetectable viral load.

On neurological examination, he scored 20/30 on the Montreal Cognitive Assessment (MoCA) and had appendicular and gait ataxia. MRI Brain T2-FLAIR revealed a diffuse leukoencephalopathy. Post gadolinium T1-weighted images demonstrated extensive perivascular/perivenular enhancement involving the subcortical and periventricular white matter. Our differential included sarcoidosis, lymphoma, autoimmune GFAP astrocytopathy, and opportunistic infections such as tuberculosis. However, systemic workup and CSF analyses for these were negative. The patient was subsequently started on prednisone for a presumed inflammatory etiology. Clinical and radiographic improvement was noted over the following weeks.

Two months later, when prednisone was tapered, his symptoms worsened, and repeat MRI showed reemergent perivascular/perivenular gadolinium enhancement. His serum viral load increased to 980 copies/mL and he had developed elvitegravir resistance, so HAART was subsequently changed to bictegravir and darunavir. Brain biopsy revealed a mild encephalitis with small vessel vasculitis with prominent CD8+ T cell involvement of the small veins and no infarctions. No infectious, granulomatous, or malignant cause was identified.

Eight weeks after the new HAART regimen was initiated, his MoCA improved to 27/30, ataxia improved, and the perivascular/perivenular enhancement resolved.

We describe a rare pattern of vasculitis and encephalitis in HIV manifesting primarily as a CD8+ T-cell perivenular inflammatory response. Our patient's clinical and radiographic response to a new HAART regimen suggests an HIV driven mechanism of vasculitis. We hypothesize his presentation emerged in response to high CSF HIV viral replication because of HAART resistance. His neuroimaging resembles previous reports of “HIV CNS escape”, a condition that is both rare and potentially treatable.