Neuropsychiatric Side Effects of Efavirenz in Children Living With HIV

Study Overview
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Brief Summary
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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.

Detailed Description
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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. .

Official Title
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Neuropsychiatric Adverse Effects of Efavirenz in Children Living With HIV in Kilimanjaro, Tanzania

Conditions
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Efavirenz, Child Behavior, Cognitive Symptom, Medication Adherence, Drug-Related Side Effects and Adverse Reactions

Intervention / Treatment
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* Drug: Efavirenz
* Drug: Nevirapine
* Drug: Lopinavir-Ritonavir Drug Combination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 6 until 12 years HIV seropositive Using cART, with or without efavirenz, for at least 6 months Registered patient at one of the participating centres In the presence of at least one parent or caregiver who is part if the child's life/upbringing Exclusion Criteria: Switch of cART regimen in the last 6 months History of brain injury, mental health and cognitive impairment before starting cART HIV RNA >1000 copies/mL within the past year Any AIDS-defining illness or acute illness (e.g. fever, lowered consciousness, dehydration) at time of inclusion Children with parent(s) or caregiver(s) not wanting or not able to give informed consent

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Efavirenz<br>Children using efavirenz-based cART for at least 6 months | Drug: Efavirenz<br>* Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS<br>* Other names: Efavirenz-group;|
| Non-efavirenz<br>Children using non-efavirenz-based cART (nevirapine or Lopinavir-Ritonavir Drug Combination) for at least 6 months. | Drug: Nevirapine<br>* Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS<br>* Other names: Non-efavirenz group;Drug: Lopinavir-Ritonavir Drug Combination<br>* Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS<br>* Other names: Non-efavirenz group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropsychological symptoms: competence and psychopathology (internalizing/externalizing symptoms) | Neuropsychological symptoms will be assessed using the Swahili version of the Child Behavior Checklist for 6-18 years (CBCL6-18) | At day of inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive functioning - non-verbal cognitive ability (general intelligence) | Non-verbal cognitive ability will be assessed using the Raven's Progressive Matrices | At day of inclusion | 
| Cognitive functioning - working memory | Working memory will be assessed using the Wechsler Intelligence Scale for Children (WISC-III) Digit Span Test | At day of inclusion | 
| Treatment adherence | Treatment adherence will be measured using an adherence questionnaire, adapted from the PENTA 16 trial (permission obtained from the author prof. Giaquinto) | At day of inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Efavirenz, Child Behavior, Cognition, Medication Adherence, Drug-Related Side Effects