Abstract

Remarkable progress was made in recent years in the therapeutics of HIV- 1-associated dementia (HAD) and in unraveling the complex pathophysiology that follows viral invasion of the central nervous system (CNS). Viral replication in and outside of the CNS was significantly reduced in HIV-1 infected subjects by new potent antiretroviral therapies. This has resulted in partial repair of cellular immune function with improvement in, and the prevention of, neurologic deficits associated with progressive HIV-1 disease. In regard to HAD pathophysiology, it is now known that CNS damage induced by HIV-1 infection occurs indirectly. Neuronal loss is mediated through immune activation and viral infection of mononuclear phagocytes (MPs) (brain macrophages and microglia). Cellular and viral factors secreted by brain MPs produce, over time, neuronal damage and drop out. Viral growth in the brain appears necessary, but not sufficient, to produce cognitive and motor impairments in affected individuals. Indeed, the best predictor for neurologic impairment following HIV-1 infection is the absolute number of immune-competent macrophages; not the level of viral production in affected brain tissue. As yet, an understanding of macrophage-related neurodegeneration has not translated into significant improvements in the treatment of this devastating complication of HIV disease. Nonetheless, adjunctive antiinflammatory and neuroprotective therapies are being developed. New ideas regarding HAD neuropathogenesis, and implications for the diagnosis and treatment of HAD are summarized in this article.

Original languageEnglish (US)
Pages (from-to)153-163
Number of pages11
JournalAIDS Patient Care and STDs
Volume13
Issue number3
DOIs
StatePublished - Jan 1 1999

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AIDS Dementia Complex
HIV-1
Dementia
Central Nervous System
Macrophages
Brain
Therapeutics
Phagocytes
HIV Infections
Microglia
Virus Diseases
Neurologic Manifestations
Nervous System
Anti-Inflammatory Agents
HIV

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

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title = "HIV-associated dementia: New insights into disease pathogenesis and therapeutic interventions",
abstract = "Remarkable progress was made in recent years in the therapeutics of HIV- 1-associated dementia (HAD) and in unraveling the complex pathophysiology that follows viral invasion of the central nervous system (CNS). Viral replication in and outside of the CNS was significantly reduced in HIV-1 infected subjects by new potent antiretroviral therapies. This has resulted in partial repair of cellular immune function with improvement in, and the prevention of, neurologic deficits associated with progressive HIV-1 disease. In regard to HAD pathophysiology, it is now known that CNS damage induced by HIV-1 infection occurs indirectly. Neuronal loss is mediated through immune activation and viral infection of mononuclear phagocytes (MPs) (brain macrophages and microglia). Cellular and viral factors secreted by brain MPs produce, over time, neuronal damage and drop out. Viral growth in the brain appears necessary, but not sufficient, to produce cognitive and motor impairments in affected individuals. Indeed, the best predictor for neurologic impairment following HIV-1 infection is the absolute number of immune-competent macrophages; not the level of viral production in affected brain tissue. As yet, an understanding of macrophage-related neurodegeneration has not translated into significant improvements in the treatment of this devastating complication of HIV disease. Nonetheless, adjunctive antiinflammatory and neuroprotective therapies are being developed. New ideas regarding HAD neuropathogenesis, and implications for the diagnosis and treatment of HAD are summarized in this article.",
author = "Susan Swindells and Zheng, {Jialin C} and Gendelman, {Howard Eliot}",
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