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

  • Stéfan Du PlessisEmail author
  • Alexander Perez
  • Jean-Paul Fouche
  • Nicole Phillips
  • John A. Joska
  • Matthijs Vink
  • Landon Myer
  • Heather J. Zar
  • Dan J. Stein
  • Jacqueline Hoare
Article

Abstract

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.

Keywords

HIV Adolescence Efavirenz fMRI 

Notes

Acknowledgment

This research was supported by NICHD under grant R01HD074051.

Author’s contribution

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.

Funding

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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Copyright information

© Journal of NeuroVirology, Inc. 2019

Authors and Affiliations

  • Stéfan Du Plessis
    • 1
    Email author
  • Alexander Perez
    • 2
  • Jean-Paul Fouche
    • 3
  • Nicole Phillips
    • 3
  • John A. Joska
    • 3
  • Matthijs Vink
    • 4
  • Landon Myer
    • 2
    • 5
  • Heather J. Zar
    • 6
    • 7
  • Dan J. Stein
    • 3
    • 8
  • Jacqueline Hoare
    • 3
  1. 1.Department of Psychiatry, Faculty of Heath SciencesStellenbosch UniversityCape TownSouth Africa
  2. 2.Division of Epidemiology and Biostatistics, School of Public Health & Family MedicineUniversity of Cape TownCape TownSouth Africa
  3. 3.Department of Psychiatry and Mental HealthUniversity of Cape TownCape TownSouth Africa
  4. 4.Departments of Experimental and Developmental PsychologyUtrecht UniversityUtrechtThe Netherlands
  5. 5.Centre for Infectious Disease Epidemiology and Research, School of Public Health & Family MedicineUniversity of Cape TownCape TownSouth Africa
  6. 6.Department of Pediatrics & Child Health, Red Cross Children’s HospitalUCTCape TownSouth Africa
  7. 7.SA Medical Research Council Unit on Child & Adolescent HealthCape TownSouth Africa
  8. 8.SA Medical Research Council Unit on Risk & Resilience in Mental DisordersCape TownSouth Africa

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