Efavirenz is associated with altered fronto-striatal function in HIV+ adolescents
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.
KeywordsHIV Adolescence Efavirenz fMRI
This research was supported by NICHD under grant R01HD074051.
SDP: Conceptualization, study design, recruitment supervision, fMRI task administration supervision, data processing, analysis, interpretation and lead author on manuscript preparation. AP: Data processing, analysis, interpretation and manuscript preparation. JPF: Conceptualization, study design, recruitment supervision, fMRI task administration supervision, data processing, analysis, interpretation and manuscript preparation. NP: Conceptualization, study design, recruitment supervision, fMRI task administration supervision and manuscript preparation. JJ: Conceptualization, study design, interpretation and manuscript preparation. MV: Task design, data processing, analysis, interpretation and manuscript preparation. LM: Conceptualization, study design, analysis, interpretation and manuscript preparation. HZ: Conceptualization, study design, interpretation and manuscript preparation. DS: Conceptualization, study design, interpretation and manuscript preparation. JH: Conceptualization, study design, interpretation and manuscript preparation.
JH has received support from the Medical Research Council (MRC) of South Africa. HZ and DS were supported by the NRF and the Medical Research Council (MRC) of South Africa.
Compliance with ethical standards
Ethical approval was obtained from the University of Cape Town’s Faculty of Health Sciences research ethics committee (HREC REF 051/2013).
Conflict of interest
The authors declare that they have no conflict of interest.
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