Open AccessEfavirenz is associated with altered fronto-striatal function in HIV+ adolescents
Author(s) -
Stéfan du Plessis,
Alexander Perez,
JeanPaul Fouché,
Nicole Phillips,
John A. Joska,
Matthijs Vink,
Landon Myer,
Heather J. Zar,
Dan J. Stein,
Jacqueline Hoare
Publication year - 2019
Publication title -
journal of neurovirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.868
H-Index - 85
eISSN - 1538-2443
pISSN - 1355-0284
DOI - 10.1007/s13365-019-00764-9
Subject(s) - efavirenz , anticipation (artificial intelligence) , neurotoxicity , psychology , human immunodeficiency virus (hiv) , viral load , medicine , antiretroviral therapy , immunology , toxicity , computer science , artificial intelligence
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.