Upregulation of microglia in drug users with and without pre-symptomatic HIV infection.

It is generally thought that infection of the central nervous system (CNS) by HIV-1 can occur early, even around the time of seroconversion, and evidence from animal studies supports this. However, the mode and timing of viral entry remain poorly understood since there have been comparatively few studies of the early neuropathology of HIV infection. In this study, samples of frontal and temporal lobes, and basal ganglia, were selected from 12 HIV-positive drug users who had been infected for 4-130 months before death, 10 HIV-negative drug users and 10 non-drug using controls, all age and sex matched. Routine and immunocytochemical staining showed that leptomeningeal and perivascular lymphocytic infiltrate was upregulated in HIV-infected cases compared with the two control groups, and choroid plexitis was confined to the HIV-positive subjects, suggesting an association with viral infection. In contrast, CD68-positive microglia were enhanced in both HIV- positive and HIV-negative drug users, considerably above the baseline seen in normal controls. However, there was no statistical difference between the three groups in relation to astrocytes. Screening and competitive polymerase chain reaction (PCR) undertaken on multiple samples including brain tissue, choroid plexus and leptomeninges from four of the HIV-positive subjects and one control case showed that the pro-viral burden was never more than 13 copies/microg DNA and was negative in multiple samples from one HIV-positive case and one control case. All the basal ganglia samples were PCR-negative. This study has not revealed any t spots' of viral load in brain tissue, choroid plexus or meninges, either early or late in the course of pre-symptomatic HIV infection. Drug use alone is associated with significant upregulation of microglia and this may predispose to HIV infection of the nervous system in drug users.