TY - JOUR
T1 - Antiretroviral Treatment with Efavirenz Disrupts the Blood-Brain Barrier Integrity and Increases Stroke Severity
AU - Bertrand, Luc
AU - Dygert, Levi
AU - Toborek, Michal
N1 - Funding Information:
ARVds were obtained from the NIH AIDS Reagent Program, Pathogenesis and Basic Research Branch, Division of AIDS NIAID. EcoHIV-NDK viral plasmid was obtained from Dr. David J. Volsky, Icahn School of Medicine at Mt. Sinai, New York, NY. This work was supported by the NIH (MH098891, MH072567, HL126559, DA039576, DA027569, and by the Miami Center for AIDS Research funded by NIH Grant MH063022). LB is supported by an AHA postdoctoral fellowship (16POST31170002).
PY - 2016/12/23
Y1 - 2016/12/23
N2 - The introduction of antiretroviral drugs (ARVd) changed the prognosis of HIV infection from a deadly disease to a chronic disease. However, even with undetectable viral loads, patients still develop a wide range of pathologies, including cerebrovascular complications and stroke. It is hypothesized that toxic side effects of ARVd may contribute to these effects. To address this notion, we evaluated the impact of several non-nucleoside reverse transcriptase inhibitors (NNRTI; Efavirenz, Etravirine, Rilpivirine and Nevirapine) on the integrity of the blood-brain barrier, and their impact on severity of stroke. Among studied drugs, Efavirenz, but not other NNRTIs, altered claudin-5 expression, increased endothelial permeability, and disrupted the blood-brain barrier integrity. Importantly, Efavirenz exposure increased the severity of stroke in a model of middle cerebral artery occlusion in mice. Taken together, these results indicate that selected ARVd can exacerbate HIV-associated cerebrovascular pathology. Therefore, careful consideration should be taken when choosing an anti-retroviral therapy regimen.
AB - The introduction of antiretroviral drugs (ARVd) changed the prognosis of HIV infection from a deadly disease to a chronic disease. However, even with undetectable viral loads, patients still develop a wide range of pathologies, including cerebrovascular complications and stroke. It is hypothesized that toxic side effects of ARVd may contribute to these effects. To address this notion, we evaluated the impact of several non-nucleoside reverse transcriptase inhibitors (NNRTI; Efavirenz, Etravirine, Rilpivirine and Nevirapine) on the integrity of the blood-brain barrier, and their impact on severity of stroke. Among studied drugs, Efavirenz, but not other NNRTIs, altered claudin-5 expression, increased endothelial permeability, and disrupted the blood-brain barrier integrity. Importantly, Efavirenz exposure increased the severity of stroke in a model of middle cerebral artery occlusion in mice. Taken together, these results indicate that selected ARVd can exacerbate HIV-associated cerebrovascular pathology. Therefore, careful consideration should be taken when choosing an anti-retroviral therapy regimen.
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U2 - 10.1038/srep39738
DO - 10.1038/srep39738
M3 - Article
C2 - 28008980
AN - SCOPUS:85007170664
VL - 6
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 39738
ER -