Neuropathogenesis of HIV-1 infection. Outstanding questions

Significant progress in understanding and treating acquired immunodeficiency syndrome (AIDS) has been made over the last 5 years. Current multi drug therapies prolong patients' lives and reduce the incidence of neurobehavioural symptoms. However, the impact of therapy on human immunodeficiency virus type one (HIV-1), the causative agent of AIDS, in the brain, is unknown. Some patients develop dementia in spite of the multi drug therapies and others develop subtle neurobehavioural changes that diminish the quality of their prolonged lives. Thus, HIV-1 infection of the central nervous system remains an important clinical concern. Although much is known about neuropathology of HIV-1 infection, major questions about neuropathogenesis remain. How does HIV-1 reach the brain? Is it present in neurons and glial cells? What is the biological and therapeutic significance of neurotropism of HIV-1? What causes neuronal damage and loss? And, is CNS a reservoir of HIV-1? More research in vivo and in situ in humans and in animals, is needed to answer these outstanding questions. Specific experiments addressing these questions are proposed.