Treatment with buprenorphine prior to EcoHIV infection of mice prevents the development of neurocognitive impairment

J Leukoc Biol. 2021 Mar;109(3):675-681. doi: 10.1002/JLB.5AB0420-531R. Epub 2020 Jun 24.

Abstract

Approximately 15-40% of people living with HIV develop HIV-associated neurocognitive disorders, HAND, despite successful antiretroviral therapy. There are no therapies to treat these disorders. HIV enters the CNS early after infection, in part by transmigration of infected monocytes. Currently, there is a major opioid epidemic in the United States. Opioid use disorder in the context of HIV infection is important because studies show that opioids exacerbate HIV-mediated neuroinflammation that may contribute to more severe cognitive deficits. Buprenorphine is an opioid derivate commonly prescribed for opiate agonist treatment. We used the EcoHIV mouse model to study the effects of buprenorphine on cognitive impairment and to correlate these with monocyte migration into the CNS. We show that buprenorphine treatment prior to mouse EcoHIV infection prevents the development of cognitive impairment, in part, by decreased accumulation of monocytes in the brain. We propose that buprenorphine has a novel therapeutic benefit of limiting the development of neurocognitive impairment in HIV-infected opioid abusers as well as in nonabusers, in addition to decreasing the use of harmful opioids. Buprenorphine may also be used in combination with HIV prevention strategies such as pre-exposure prophylaxis because of its safety profile.

Keywords: inflammation; monocytes; neuroAIDS; opioids; water maze.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AIDS Dementia Complex / complications
  • AIDS Dementia Complex / prevention & control*
  • AIDS Dementia Complex / virology
  • Animals
  • Antigens, Ly / metabolism
  • Brain / pathology
  • Buprenorphine / pharmacology
  • Buprenorphine / therapeutic use*
  • Chronic Disease
  • Cognitive Dysfunction / complications
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / prevention & control
  • Cognitive Dysfunction / virology
  • Disease Models, Animal
  • HIV Infections / drug therapy*
  • Inflammation / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / drug effects
  • Phenotype
  • Viral Load / drug effects

Substances

  • Antigens, Ly
  • Ly-6C antigen, mouse
  • Buprenorphine