HIV encephalitis, proviral load and dementia in drug users and homosexualswith AIDS - Effect of neocortical involvement

In this consecutive autopsy study, the pathological evidence of HIV encepha litis, which included the presence of giant cells and/or HIV p24 immunoposi tivity, was found more frequently in drug users (25 of 45; 56%) than in hom osexual men (6 of 35; 17%) with AIDS (P < 0.01). Productive infection, as s hown by HIV p24 positivity, was found in frontal lobe white matter in 29 of the 31 HIV encephalitis cases, but was also present in grey matter in 50% of the HIV encephalitis cases. Immunopositivity was confined to microglia, monocytes and most but not all giant cells, HIV-1 proviral load was determi ned by quantitative PCR in 65 of the 80 cases (separately in grey and white matter in 49 of these), and correlated well with the presence of HIV encep halitis (P < 0.001). Twenty-five patients with AIDS (13 male homosexuals, 1 2 drug users) showed no HIV encephalitis, opportunistic infection or cerebr al lymphoma, while 18 (2 male homosexuals, 1.6 drug users) showed pure HIV encephalitis. Cognitive function had been assessed prospectively in this co hort and graded as normal or mildly, moderately or severely impaired. Becau se opportunistic infections and lymphomas of the brain may also lead to dem entia, patients found to have these conditions at autopsy were excluded fro m the final analysis of the cases with dementia, so that the precise correl ation between cognitive impairment and pure HIV encephalitis could be deter mined in this cohort without possible confounding variables. Fourteen of 18 patients with pure HIV encephalitis had shown cognitive impairment. Severe dementia correlated better with pure HIV encephalitis in cases in which gr ey matter involvement was present (7 out of 9) than in those in which only white matter was involved (2 out of 9) (P < 0.05), although milder degrees of cognitive impairment had been present in a further 5 HIV encephilitis ca ses. No correlation was found between zidovudine therapy and the degree of cognitive impairment, Systemic and cerebral opportunistic infections and ly mphoma showed a negative association with HIV encephalitis, being more comm on in homosexuals than in drug users, despite comparable CD4 counts in; the two groups, These findings suggest that neocortical productive HIV infecti on is a significant factor in AIDS-related dementia, although this may refl ect merely a higher overall viral burden in the brain.