HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment

Nat Rev Neurol. 2016 Apr;12(4):234-48. doi: 10.1038/nrneurol.2016.27. Epub 2016 Mar 11.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-HIV Agents / therapeutic use
  • Anti-Inflammatory Agents / therapeutic use
  • Cognition Disorders / diagnosis
  • Cognition Disorders / epidemiology*
  • Cognition Disorders / therapy*
  • HIV Infections / diagnosis
  • HIV Infections / epidemiology*
  • HIV Infections / therapy*
  • Humans
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / epidemiology*
  • Nervous System Diseases / therapy*
  • Risk Factors
  • Treatment Outcome


  • Anti-HIV Agents
  • Anti-Inflammatory Agents

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