Neuroinflammation has an established link with AIDS-related dementia but has not been investigated in the post-highly active anti-retroviral therapy (HAART) era. In this autopsy study we examined post-HAART cases in Edinburgh for the presence of HIV-related pathology and in well-treated cases for evidence of neuroinflammation. We focused on basal ganglia and the hippocampus, 2 key areas of the brain for cognitive functioning and compared pre- and post-HAART cases for neuroinflammatory status. We find evidence, post-HAART, that there is a high level of microglial/macrophage activation that is comparable with the levels seen, pre-HAART, in HIV encephalitis (HIVE) and AIDS cases. This result was maximal in the hippocampus where microglial/macrophage upregulation in the HAART-treated group exceeded that seen in HIVE. In the basal ganglia, HAART-treated cases showed significantly higher levels of CD68-positive microglia/macrophages than in control brains (p = 0.004), and in the hippocampus levels were significantly higher than those seen in control cases, pre-HAART AIDS, and presymptomatic brains (p = 0.01). However, lymphocyte levels in the areas examined were low in HAART-treated cases. We conclude that there is a surprising degree of ongoing neuroinflammation in HAART-treated patients, particularly in the hippocampus. This may pose a threat for the future health of individuals maintained long-term on HAART therapy.

Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

No abstract

The introduction of Highly Active Anti-retroviral Therapy (HAART) has resulted in significant decreases in morbidity and mortality for subjects infected with HIV. The brain is a major target organ for HIV resulting in significant neuropathological changes in most HIV infected subjects and a wide range of clinical neurological symptoms including HIV associated dementia. In the pre-HAART era HIV associated dementia was a common complication of AIDS. However, since the introduction of HAART the incidence of HIV associated dementia has fallen, but the prevelance has actually risen due to the increasing number of infected subjects and increased life expectancy. HIV associated dementia correlates most closely with neuroinflammation rather than directly with viral load or HIV encephalitis. HIV related clinical and neuropathological disorders are more prevalent in drug abusers than in other risk groups. This review focuses on the shifting pathology observed in HIV infected subjects since the introduction of HAART, discussing the clinical manifestations of these and the influence of confounding factors such as drug abuse and Hepatitis C co-infection.