Cerebral Vascular Toxicity of Antiretroviral Therapy

J Neuroimmune Pharmacol. 2021 Mar;16(1):74-89. doi: 10.1007/s11481-019-09858-x. Epub 2019 Jun 17.

Abstract

HIV infection is associated with comorbidities that are likely to be driven not only by HIV itself, but also by the toxicity of long-term use of antiretroviral therapy (ART). Indeed, increasing evidence demonstrates that the antiretroviral drugs used for HIV treatment have toxic effects resulting in various cellular and tissue pathologies. The blood-brain barrier (BBB) is a modulated anatomophysiological interface which separates and controls substance exchange between the blood and the brain parenchyma; therefore, it is particularly exposed to ART-induced toxicity. Balancing the health risks and gains of ART has to be considered in order to maximize the positive effects of therapy. The current review discusses the cerebrovascular toxicity of ART, with the focus on mitochondrial dysfunction. Graphical Abstract Graphical representation of the interactions between HIV, antiretroviral therapy (ART), and the blood-brain barrier (BBB).

Keywords: Antiretroviral therapy; Blood-brain barrier; Cerebrovascular toxicity; Mitochondria; Neurotoxicity.

Publication types

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

MeSH terms

  • AIDS Dementia Complex / drug therapy
  • AIDS Dementia Complex / etiology
  • ATP Binding Cassette Transporter, Subfamily B / physiology
  • Aging
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / pharmacokinetics
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Biological Transport
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / physiology
  • DNA Polymerase gamma / physiology
  • DNA, Mitochondrial / metabolism
  • Drug Resistance
  • HIV Infections / drug therapy
  • HIV Infections / physiopathology
  • HIV-1 / pathogenicity
  • Humans
  • Inflammation
  • Mitochondria / pathology
  • Models, Biological
  • Nervous System Diseases / chemically induced
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / pathology
  • Organ Specificity

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • Anti-HIV Agents
  • DNA, Mitochondrial
  • DNA Polymerase gamma