Efavirenz is associated with altered fronto-striatal function in HIV+ adolescents.

Journal: Journal of neurovirology

Volume: 25

Issue: 6

Year of Publication: 2020

Affiliated Institutions:  Department of Psychiatry, Faculty of Heath Sciences, Stellenbosch University, Francie van Zijl Avenue, Tygerberg, Cape Town, South Africa. stefandup@sun.ac.za. Division of Epidemiology and Biostatistics, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa. Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa. Departments of Experimental and Developmental Psychology, Utrecht University, Utrecht, The Netherlands. Department of Pediatrics & Child Health, Red Cross Children's Hospital, UCT, Cape Town, South Africa.

Abstract summary 

Neurotoxicity associated with the antiretroviral efavirenz (EFV) has been documented in HIV-infected adults, but there are no data on the impact of EFV on brain function in adolescents. We investigated potential alterations in fronto-striatal function associated with EFV use in adolescents. A total of 86 adolescents underwent a Stop Signal Anticipation Task (SSAT) during functional MRI (fMRI), 39 HIV+ adolescents receiving EFV, 27 HIV+ adolescents on antiretroviral therapy without EFV (matched on age, gender, education, CD4 cell count and HIV viral load) and 20 HIV- matched controls (matched on age and gender). The task required participants to give timed GO responses with occasional STOP signals at fixed probabilities. Reactive inhibition was modelled as a correct STOP response and proactive inhibition was modelled after response slowing as the STOP probability increases. A priori mask-based regions associated with reactive and proactive inhibition were entered into two respective multivariate ANOVAs. The EFV treatment group showed significantly blunted proactive inhibitory behavioural responses compared to HIV+ adolescents not receiving EFV. There was no difference in reactive inhibition between treatment groups. We also demonstrated a significant effect of EFV treatment on BOLD signal in proactive inhibition regions. There was no difference in regions involved in reactive inhibition. We found no differences between adolescents not receiving EFV and HIV- controls, showing that functional and behavioural differences were unique to the EFV group. Here, we demonstrate for the first time a potential adverse impact of EFV on higher cortical function in young HIV+ adolescents.

Authors & Co-authors:  Du Plessis Stéfan S Perez Alexander A Fouche Jean-Paul JP Phillips Nicole N Joska John A JA Vink Matthijs M Myer Landon L Zar Heather J HJ Stein Dan J DJ Hoare Jacqueline J

Study Outcome 

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Statistics
Citations :  Arend C, Rother A, Stolte S, Dringen R (2016) Consequences of a Chronic Exposure of Cultured Brain Astrocytes to the Anti-Retroviral Drug Efavirenz and its Primary Metabolite 8-Hydroxy Efavirenz. Neurochem Res 41:3278–3288. doi: 10.1007/s11064-016-2059-x
Authors :  10
Identifiers
Doi : 10.1007/s13365-019-00764-9
SSN : 1538-2443
Study Population
Male,Female
Mesh Terms
Alkynes
Other Terms
Adolescence;Efavirenz;HIV;fMRI
Study Design
Cross Sectional Study
Study Approach
Country of Study
Publication Country
United States