HIV-associated neurocognitive disorder - Pathogenesis and prospects for treatment

Research output: Contribution to journalArticle

Abstract

In the past two decades, several advancements have improved the care of HIV-infected individuals. Most importantly, the development and deployment of combination antiretroviral therapy (CART) has resulted in a dramatic decline in the rate of deaths from AIDS, so that people living with HIV today have nearly normal life expectancies if treated with CART. The term HIV-associated neurocognitive disorder (HAND) has been used to describe the spectrum of neurocognitive dysfunction associated with HIV infection. HIV can enter the CNS during early stages of infection, and persistent CNS HIV infection and inflammation probably contribute to the development of HAND. The brain can subsequently serve as a sanctuary for ongoing HIV replication, even when systemic viral suppression has been achieved. HAND can remain in patients treated with CART, and its effects on survival, quality of life and everyday functioning make it an important unresolved issue. In this Review, we describe the epidemiology of HAND, the evolving concepts of its neuropathogenesis, novel insights from animal models, and new approaches to treatment. We also discuss how inflammation is sustained in chronic HIV infection. Moreover, we suggest that adjunctive therapies - treatments targeting CNS inflammation and other metabolic processes, including glutamate homeostasis, lipid and energy metabolism - are needed to reverse or improve HAND-related neurological dysfunction.

Original languageEnglish (US)
Pages (from-to)234-248
Number of pages15
JournalNature Reviews Neurology
Volume12
Issue number4
DOIs
StatePublished - Apr 1 2016

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HIV
HIV Infections
Therapeutics
Inflammation
Neurocognitive Disorders
Life Expectancy
Lipid Metabolism
Energy Metabolism
Glutamic Acid
Acquired Immunodeficiency Syndrome
Epidemiology
Homeostasis
Animal Models
Quality of Life
Survival
Mortality
Brain
Infection

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

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abstract = "In the past two decades, several advancements have improved the care of HIV-infected individuals. Most importantly, the development and deployment of combination antiretroviral therapy (CART) has resulted in a dramatic decline in the rate of deaths from AIDS, so that people living with HIV today have nearly normal life expectancies if treated with CART. The term HIV-associated neurocognitive disorder (HAND) has been used to describe the spectrum of neurocognitive dysfunction associated with HIV infection. HIV can enter the CNS during early stages of infection, and persistent CNS HIV infection and inflammation probably contribute to the development of HAND. The brain can subsequently serve as a sanctuary for ongoing HIV replication, even when systemic viral suppression has been achieved. HAND can remain in patients treated with CART, and its effects on survival, quality of life and everyday functioning make it an important unresolved issue. In this Review, we describe the epidemiology of HAND, the evolving concepts of its neuropathogenesis, novel insights from animal models, and new approaches to treatment. We also discuss how inflammation is sustained in chronic HIV infection. Moreover, we suggest that adjunctive therapies - treatments targeting CNS inflammation and other metabolic processes, including glutamate homeostasis, lipid and energy metabolism - are needed to reverse or improve HAND-related neurological dysfunction.",
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