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Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is elevated in cerebrospinal fluid in HIV- associated dementia; in addition, therapeutic GM-CSF elevates plasma viral load., Objective: To assess the effect of GM-CSF on viral replication and the potential ameliorative effect of antiretroviral therapy., Design: A primary human brain aggregate system is used as a model of the in vivo situation., Method: Cultured aggregates were infected with the macrophage tropic strain HIV-1SF162 and then exposed to varying GM-CSF concentrations and 0.3 micromol/l stavudine. Viral replication was assessed by p24 expression in the supernatant and aggregates. Immunohistochemistry identified neurons, astrocytes, microglia and oligodendrocytes., Results: A GM-CSF concentration of 1 ng/ml resulted in a fivefold increase in microglial cells, the main HIV cellular reservoir (P = 0.0001). Prior GM-CSF exposure before infection of the aggregates resulted in sixfold increase in p24 levels compared with non-GM-CSF-exposed infected aggregates. Infected aggregates with or without GM-CSF had significant neuronal loss of 50% and 45%, respectively, and astrocytosis. Addition of stavudine to the infected aggregates, even in the presence of GM-CSF, reduced p24 levels to zero and prevented neuronal loss and astrocytosis., Conclusions: This study demonstrates that GM-CSF enhances viral replication while addition of stavudine prevents this potentially detrimental process.

Objectives: To examine the epidemiology of HIV-associated neuropathology in the United Kingdom and to investigate whether the prevalence of different forms of HIV-associated brain pathology varies with exposure category., Design: The study was a cross-sectional survey; data was analysed from the Medical Research Council National AIDS Neuropathology database., Setting: Information was gathered from throughout England, Scotland and Wales., Subjects: Individuals who died from AIDS in the United Kingdom and had a postmortem examination. The database comprised 7% of all AIDS deaths in the United Kingdom between 1982 and 1993., Main Outcome: Neuropathological diagnoses based on internationally accepted neuropathological terminology of AIDS-related brain lesions., Results: HIV encephalitis was the most prevalent pathological diagnosis, occurring in 25.3% [95% confidence interval (CI), 21.0-29.6] of the study sample. Statistically significant independent associations for the occurrence of HIV encephalitis were found for injecting drug use (odds ratio, 6.86; 95% CI, 2.91-16.17), and age less than 30 years at death (odds ratio, 3.58; 95% CI, 1.99-6.44). Vascular lesions were significantly higher among blood product recipients, 95% of whom were haemophiliacs., Conclusions: This was the first epidemiological investigation of HIV-associated brain pathology in the United Kingdom. HIV encephalitis appeared to occur more frequently in injecting drug users and those who died younger. Whereas the findings must be interpreted cautiously, one hypothesis was that differences in the route of transmission may have affected the manifestation of HIV-associated brain damage.