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The Persistence of HIV-Associated Neurocognitive Disorder (HAND) in the Era of Combined Antiretroviral Therapy (cART)

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Global Virology II - HIV and NeuroAIDS

Abstract

HIV invades the CNS compartment very early in infection and infects monocytes, microglia, macrophages, and astrocytes. These cells comprise the CNS viral reservoir. Neuroinvasion can continue throughout the infected individual’s lifetime due to the migration of HIV-infected monocytes across the blood-brain barrier (BBB). Infection of the CNS stimulates the activation of both infected and uninfected cells, the production of neurotoxic viral proteins, the expression of chemokines which attract additional infected monocytes, and a persistent CNS inflammation that causes neuronal dysfunction and death. These events are responsible for the neurocognitive, motor, and behavioral deficits collectively known as HIV-associated neurocognitive disorder (HAND). Treatment with combined antiretroviral therapy (cART) reduces the pool of replicating virus and may also reduce inflammation; however, current cART cannot eradicate the CNS viral reservoir nor persistent CNS inflammation, as HIV has molecular mechanisms of evading the immune system and may also be protected from therapeutic levels of cART within the CNS. Thus, cART attenuates rather than cures the brain pathology underlying HAND. In addition, comorbid processes such as aging, cART neurotoxicity, drug use, HCV coinfection, and vascular risk factors may contribute to brain injury and exacerbate the manifestations of HAND.

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Authors and Affiliations

  1. Department of Neurology, David Geffen School of Medicine, and National Neurological AIDS Bank (NNAB), University of California, Los Angeles, CA, USA

    Elyse J. Singer MD & Natasha M. Nemanim

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  1. Elyse J. Singer MD
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  2. Natasha M. Nemanim
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Correspondence to Elyse J. Singer MD .

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Editors and Affiliations

  1. Department of Internal Medicine, Division of Infectious Diseases and International Health, University of South Florida, Tampa, Florida, USA

    Paul Shapshak

  2. Department of Neurology, UCLA David Geffen School of Medicine, Los Angeles, California, USA

    Andrew J. Levine

  3. Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico, USA

    Brian T. Foley

  4. Department of Internal Medicine, Division of Infectious Diseases and International Health, University of South Florida, Morsani College of Medicine, Tampa, Florida, USA

    Charurut Somboonwit

  5. Department of Neurology, UCLA David Geffen School of Medicine, Los Angeles, California, USA

    Elyse Singer

  6. Department of Oral Biology and Medicine, UCLA School of Dentistry, Los Angeles, California, USA

    Francesco Chiappelli

  7. Department of Internal Medicine, Division of Infectious Diseases and International Health, University of South Florida, Morsani College of Medicine, Tampa, Florida, USA

    John T. Sinnott

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Singer, E.J., Nemanim, N.M. (2017). The Persistence of HIV-Associated Neurocognitive Disorder (HAND) in the Era of Combined Antiretroviral Therapy (cART). In: Shapshak, P., et al. Global Virology II - HIV and NeuroAIDS. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7290-6_16

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