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

Cerebral Vascular Toxicity of Antiretroviral Therapy

Luc Bertrand #  1 , Martina Velichkovska #  1 , Michal Toborek  2
Affiliations
Review

Cerebral Vascular Toxicity of Antiretroviral Therapy

Luc Bertrand et al. J Neuroimmune Pharmacol. 2021 Mar.

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Graphical Abstract
Graphical Abstract
Graphical representation of the interactions between HIV, antiretroviral therapy (ART), and the blood-brain barrier (BBB).
Fig. 1
Fig. 1
Blood-brain barrier dysfunction in HIV-infected patients. Visual representation of the mechanisms leading to BBB disruption in HIV infection
Fig. 2
Fig. 2
Alterations of BBB functionality as the result of exposure to antiretroviral drugs. Alterations (red arrow: decrease; green arrow: increase) of cellular processes at the level of the BBB resulting from exposure to antiretroviral drugs. (LPV: lopinavir; EFV: efavirenz; SQV: saquinavir; ATV: ataznavir; RTV: ritonavir; ZDV: zidovudine; IDV: indinavir; TDF: tenofovir; FTC: emtricitabine; MVC: maraviroc; RAL: raltegravir; DRV: darunavir)
Fig. 3
Fig. 3
Factors contributing and exacerbating mitochondrial dysfunction as the result of exposure to antiretroviral drugs. Supplemental therapy targeting the exacerbating factors can prevent the onset of mitochondrial dysfunction
Fig. 4
Fig. 4
Onset of mitochondrial dysfunction as a function of time and susceptibility of individual cell types to lifetime exposure to antiretroviral drugs
See this image and copyright information in PMC

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