Neuropsychiatric Side Effects of Efavirenz in Children Living With HIV
Study Details
Study Description
Brief Summary
Efavirenz is among the preferred antiretroviral drugs for HIV-infected children. Increasing evidence shows that central nervous system side-effects in adults are more common than previously thought. Still, reliable data in children are lacking. As HIV-infected children nowadays have a prospect of reaching adulthood, there is an urgent need to identify potential long-term central nervous system side-effects, interfering with neurodevelopment and psychosocial maturation. Using validated tools, we assessed (1) competence (social/activities/school) and psychopathology (internalizing/externalizing problems), (2) cognitive performance (intelligence and working memory), and (3) adherence in Tanzanian children on an efavirenz or non-efavirenz based regimen
In this cross-sectional observational study the investigators will examine neuropsychiatric and neurocognitive functioning in 126 children (aged 6-11 years) on long-term combination antiretroviral therapy (cART) with or without efavirenz.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
In this cross-sectional observational study, we include HIV-infected children (6-12 years) on cART for ≥ 6 months, with viral loads ≤ 1000 copies/ml in Kilimanjaro Region, Tanzania. Psychopathology and competence will be assessed using the Child Behaviour Checklist. Cognitive performance will be assessed using the Raven's Coloured Progressive Matrices and the digit span test. Non-adherence is defined as any reported missed doses over the previous 3 days or <100% adherence since the last clinical visit. Analysis of covariance and logistic regression models will be used to assess differences between groups. .
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Efavirenz Children using efavirenz-based cART for at least 6 months |
Drug: Efavirenz
Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS
Other Names:
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| Non-efavirenz Children using non-efavirenz-based cART (nevirapine or Lopinavir-Ritonavir Drug Combination) for at least 6 months. |
Drug: Nevirapine
Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS
Other Names:
Drug: Lopinavir-Ritonavir Drug Combination
Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Neuropsychological symptoms: competence and psychopathology (internalizing/externalizing symptoms) [At day of inclusion]
Neuropsychological symptoms will be assessed using the Swahili version of the Child Behavior Checklist for 6-18 years (CBCL6-18)
Secondary Outcome Measures
- Cognitive functioning - non-verbal cognitive ability (general intelligence) [At day of inclusion]
Non-verbal cognitive ability will be assessed using the Raven's Progressive Matrices
- Cognitive functioning - working memory [At day of inclusion]
Working memory will be assessed using the Wechsler Intelligence Scale for Children (WISC-III) Digit Span Test
- Treatment adherence [At day of inclusion]
Treatment adherence will be measured using an adherence questionnaire, adapted from the PENTA 16 trial (permission obtained from the author prof. Giaquinto)
Other Outcome Measures
- Central nervous system symptoms [At day of inclusion]
The presence of central nervous system symptoms (yes/no) in the week prior to study visit will be assessed using a checklist composed of symptoms that have been linked to efavirenz in literature.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Aged 6 until 12 years
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HIV seropositive
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Using cART, with or without efavirenz, for at least 6 months
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Registered patient at one of the participating centres
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In the presence of at least one parent or caregiver who is part if the child's life/upbringing
Exclusion Criteria:
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Switch of cART regimen in the last 6 months
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History of brain injury, mental health and cognitive impairment before starting cART
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HIV RNA >1000 copies/mL within the past year
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Any AIDS-defining illness or acute illness (e.g. fever, lowered consciousness, dehydration) at time of inclusion
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Children with parent(s) or caregiver(s) not wanting or not able to give informed consent
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Kilimanjaro Christian Medical Centre | Moshi | Kilimanjaro Region | Tanzania | 3010 |
| 2 | Mawenzi Regional Hospital | Moshi | Kilimanjaro Region | Tanzania | 3054 |
| 3 | Kibosho Hospital | Kibosho | Tanzania | ||
| 4 | Kiboroloni Dispensary | Moshi | Tanzania | ||
| 5 | Majengo Health Centre | Moshi | Tanzania | ||
| 6 | Pasua Health Centre | Moshi | Tanzania |
Sponsors and Collaborators
- Radboud University Medical Center
- Kilimanjaro Christian Medical Centre, Tanzania
- Kilimanjaro Clinical Research Institute
Investigators
- Principal Investigator: Grace Kinabo, MD, PhD, Kilimanjaro Christian Medical Centre
- Principal Investigator: André van der Ven, MD, PhD, Radboud University Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
- Mothapo KM, Schellekens A, van Crevel R, Keuter M, Grintjes-Huisman K, Koopmans P, van der Ven A. Improvement of Depression and Anxiety After Discontinuation of Long- Term Efavirenz Treatment. CNS Neurol Disord Drug Targets. 2015;14(6):811-8.
- Van de Wijer L, Kinabo GD, Mchaile DN, de Mast Q, Schellekens AFA, van der Ven AJAM. Safety Evaluation of Efavirenz in Children: Don't Forget the Central Nervous System. Clin Infect Dis. 2018 Mar 19;66(7):1150. doi: 10.1093/cid/cix926.
- Van de Wijer L, Schellekens AFA, Burger DM, Homberg JR, de Mast Q, van der Ven AJAM. Rethinking the risk-benefit ratio of efavirenz in HIV-infected children. Lancet Infect Dis. 2016 May;16(5):e76-e81. doi: 10.1016/S1473-3099(16)00117-1. Epub 2016 Apr 18. Review.
- EFV Kids