Influence of risk group and zidovudine therapy on the development of HIV encephalitis and cognitive impairment in AIDS patients

Objective: To determine the associations between HIV encephalitis and other central nervous system (CNS) pathology, viral burden, cognitive impairment, zidovudine therapy and risk group in AIDS patients. Design: Planned autopsy study in AIDS patients evaluated prospectively for numerous clinical parameters. Setting: Regional academic centre for clinical care and pathology examination of patients with HIV infection. Patients: Edinburgh cohort of HIV-positive patients prospectively assessed for cognitive impairment, immunosuppression and clinical course. Unbiased series of consecutive autopsies in 27 homosexual men and 39 drug-using patients with AIDS. Interventions: Zidovudine therapy monitored in all patients. Main outcome measures: Determination of CNS viral burden and pathology including immunocytochemically confirmed HIV encephalitis in injecting drug users (IDU) versus homosexual AIDS patients with known CD4 counts and cognitive function. Results: HIV encephalitis was present in 59% of IDU and 15% of homosexuals: 88% of patients with encephalitis had displayed cognitive impairment. HIV encephalitis was strongly associated with a high viral load and HIV p24 immunopositivity. Opportunistic infections and lymphomas were more common in homosexuals (63%) than in IDU (31%) and were associated with the degree of immunosuppression before death. Within both groups, prolonged zidovudine treatment was associated with a lower incidence of HIV encephalitis. Conclusions: This study documents two separate CNS outcomes in AIDS patients in that HIV encephalitis occurs independently of opportunistic infections and lymphomas and shows different associations with risk group, immunosuppression and antiviral treatment before death.