Developments in HIV Neuropathogenesis

Avindra      Nath; Jeffrey   A.   Rumbaugh

Abstract

Despite the fact that neurons are rarely infected by the human immunodeficiency virus (HIV), neuronal loss is common in patients with HIV infection, likely due to the effects of viral proteins and inflammatory mediators on these cells. Despite the widespread use of highly active antiretroviral therapy (HAART), at least in developed nations, cognitive impairment and other neurological complications of HIV infection persist with devastating personal and socioeconomic consequences. Fortunately, we have made important advances in recent years in defining the molecular mechanisms by which HIV infection targets the nervous system for damage. Such understanding has opened numerous therapeutic options, which are only now beginning to be exploited. This review will highlight the current state of thought regarding the neuropathogenesis of HIV infection. It will summarize the most recent research looking at the roles of both viral and host factors in mediating HIV-induced neurological disease. Utilizing this knowledge base, a framework will be outlined for current and future therapeutic trials to prevent or improve neurological complications of HIV infection.

Keywords: HIV dementia, Tat, gp120, MMP, TNF, cytokines, blood brain barrier, HAART