Journal of NeuroVirology

, Volume 25, Issue 5, pp 622–633 | Cite as

Pathogenesis of age-related HIV neurodegeneration

  • Miroslaw (Mack) Mackiewicz
  • Cassia Overk
  • Cristian L. Achim
  • Eliezer MasliahEmail author


People over the age of 50 are the fastest growing segment of the HIV-infected population in the USA. Although antiretroviral therapy has remarkable success controlling the systemic HIV infection, HIV-associated neurocognitive disorder (HAND) prevalence has increased or remained the same among this group, and cognitive deficits appear more severe in aged patients with HIV. The mechanisms of HAND in the aged population are not completely understood; a leading hypothesis is that aged individuals with HIV might be at higher risk of developing Alzheimer’s disease (AD) or one of the AD-related dementias (ADRD). There are a number of mechanisms through which chronic HIV disease alone or in combination with antiretroviral therapy and other comorbidities (e.g., drug use, hepatitis C virus (HCV)) might be contributing to HAND in individuals over the age of 50 years, including (1) overlapping pathogenic mechanisms between HIV and aging (e.g., decreased proteostasis, DNA damage, chronic inflammation, epigenetics, vascular), which could lead to accelerated cellular aging and neurodegeneration and/or (2) by promoting pathways involved in AD/ADRD neuropathogenesis (e.g., triggering amyloid β, Tau, or α-synuclein accumulation). In this manuscript, we will review some of the potential common mechanisms involved and evidence in favor and against a role of AD/ADRD in HAND.


Aging Alzheimer’s disease HIV-associated cognitive impairment Neurodegeneration 



The authors thank Drs. Jorge R. Barrio, Vladimir Kepe, and Harry V. Vinters at UCLA, and the HIV Neurobehavioral Research Program Developmental Core at UCSD.

Funding information

This study received funding from R01MH105319-04 to CLA.


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Copyright information

© Journal of NeuroVirology, Inc. 2019

Authors and Affiliations

  • Miroslaw (Mack) Mackiewicz
    • 1
  • Cassia Overk
    • 2
  • Cristian L. Achim
    • 3
  • Eliezer Masliah
    • 1
    • 4
    Email author
  1. 1.Division of NeuroscienceNational Institute on Aging/NIHBethesdaUSA
  2. 2.Department of NeurosciencesUniversity of California San DiegoLa JollaUSA
  3. 3.Department of PsychiatryUniversity of California San DiegoLa JollaUSA
  4. 4.Laboratory of NeurogeneticsNational Institute on Aging/NIHBethesdaUSA

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