HIV mediates a productive infection of the brain

BACKGROUND: Approximately one quarter of patients with AIDS develop severe cognitive deficits called HIV-associated dementia complex. There is some controversy regarding the importance of viral load and distribution in mediating this neurologic disease. OBJECTIVE: Brain HIV proviral and RNA loads were compared to define the molecular nature of HIV infection of the brain. METHOD: Neuropathologic examination was performed on brains from 10 autopsies of patients with AIDS that had short post-mortem intervals and no evidence of opportunistic infection. Viral DNA and RNA were extracted and quantified from multiple brain regions. These findings were compared with triple-label immunofluorescence for viral and cell markers. RESULTS: Brains with histopathologic evidence of HIV encephalitis contained abundant HIV RNA and DNA. Regions without productive HIV infection showed minimal proviral load. By immunocytochemistry, only brain macrophages/microglia double labeled for viral proteins. CONCLUSIONS: HIV mediates a productive infection of brain macrophages/microglia. There was no evidence supporting the hypothesis of substantial neuronal or macroglial infection, or evidence of substantial proviral burden prior to the development of productive infection.