ABSTRACT
I. INTRODUCTION Human immunodeficiency virus-1 (HIV-1), in addition to destroying the immune system, can also induce neurological disease that culminates in frank dementia. The worldwide development of HIV-related disease is alarming, with more than 36 million existing infections and about 20 million deaths [1]. HIV infection with acquired immunodeficiency syndrome (AIDS) opportunistic infections may affect the central nervous system (CNS), but the virus itself can also induce a number of neurological syndromes [2]. Neuropathological conditions directly triggered by HIV-1 include peripheral neuropathies, vacuolar myelopathy, and a syndrome of cognitive and motor dysfunction that has been designated HIV-associated dementia (HAD) [2]. A mild form of HAD is called minor cognitive motor disorder (MCMD) [2,3]. This chapter reviews recent developments in HIV-1-associated disease of the CNS, in particular HAD and MCMD. The mechanisms of HAD and MCMD remain poorly understood, but the discovery in the brain of cellular binding sites for HIV-1, the chemokine receptors, promises new insights. Interestingly, HIV-1 in the brain productively infects only macrophages and microglia, but injury and apoptotic death occur in neurons. Neurotoxins from macrophages, microglia, and astrocytes constitute the predominant pathway to neuronal injury, though direct effects of viral proteins might contribute. The released neurotoxic factors excessively stimulate neurons, thus leading to excitotoxicity with subsequent breakdown in neurons of vital cellular functions in a manner shared with other neurodegenerative diseases. Advances in understanding the molecular mechanisms of the disease-defining events provide hope for improved therapeutic intervention.
