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Updated: Feb 12, 2026

Quantification of Cerebral Vascular Architecture using Two-photon Microscopy in a Mouse Model of HIV-induced Neuroinflammation
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HIV-associated neurocognitive disorder.

Ruaridh Cameron Smail1, Bruce James Brew2

  • 1Department of Neurology, St. Vincent's Hospital, Sydney, NSW, Australia.

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Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) impacts millions, causing cognitive decline. Ongoing research explores CNS inflammation and aging

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Area of Science:

  • Neuroscience
  • Infectious Diseases
  • Gerontology

Background:

  • Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) affects approximately 50% of the HIV-positive population, manifesting as cognitive slowing, poor concentration, and memory issues.
  • Diagnosis involves identifying deficits in two cognitive domains via neuropsychological testing, supported by imaging and lab tests, though specific biomarkers are lacking.
  • Combined antiretroviral therapy has reduced severe HAND cases but increased milder forms, highlighting persistent central nervous system (CNS) inflammation despite viral suppression.

Purpose of the Study:

  • To investigate the causes of ongoing CNS inflammation and neuronal dysfunction in HIV-positive individuals with durable viral suppression.
  • To understand the accelerating impact of aging and comorbidities on HAND in the context of chronic HIV infection.
  • To explore the development of novel, non-neurotoxic CNS-targeted therapies for HAND prevention and treatment.

Main Methods:

  • Neuropsychological testing to assess cognitive domains.
  • Neuroimaging and cerebrospinal fluid analysis for corroborating evidence.
  • Analysis of the interaction between aging, comorbidities, and chronic HIV infection on cognitive function.

Main Results:

  • Milder forms of HAND are rising in prevalence despite effective systemic antiretroviral therapy.
  • Ongoing CNS inflammation and neuronal dysfunction persist even with controlled systemic viral load.
  • Aging and comorbidities exacerbate cognitive impairment in the context of chronic HIV infection.

Conclusions:

  • Understanding the mechanisms of CNS inflammation is crucial for managing HAND.
  • Developing targeted, safe CNS therapies is essential for improving HAND outcomes.
  • The interplay of aging and comorbidities significantly influences HAND progression in the HIV-positive population.