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| Name | Class |
|---|---|
| Kilimanjaro Christian Medical Centre, Tanzania | OTHER |
| Kilimanjaro Clinical Research Institute | OTHER |
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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.
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. .
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Efavirenz | Children using efavirenz-based cART for at least 6 months |
| |
| Non-efavirenz | Children using non-efavirenz-based cART (nevirapine or Lopinavir-Ritonavir Drug Combination) for at least 6 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Efavirenz | Drug | Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS |
|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Central nervous system symptoms | 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. | At day of inclusion |
Inclusion Criteria:
Exclusion Criteria:
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Tanzanian children (6-12 years) living with HIV and receiving cART
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| Name | Affiliation | Role |
|---|---|---|
| Grace Kinabo, MD, PhD | Kilimanjaro Christian Medical Centre | Principal Investigator |
| André van der Ven, MD, PhD | Radboud University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kilimanjaro Christian Medical Centre | Moshi | Kilimanjaro | 3010 | Tanzania | ||
| Mawenzi Regional Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27599655 | Background | 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. | |
| 25808896 | Background | 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. doi: 10.2174/1871527314666150325235847. |
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| Nevirapine | Drug | Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS |
|
|
| Lopinavir-Ritonavir Drug Combination | Drug | Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS |
|
|
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 |
| Moshi |
| Kilimanjaro |
| 3054 |
| Tanzania |
| Kibosho Hospital | Kibosho | Tanzania |
| Kiboroloni Dispensary | Moshi | Tanzania |
| Majengo Health Centre | Moshi | Tanzania |
| Pasua Health Centre | Moshi | Tanzania |
| 29088326 | Background | 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. No abstract available. |
| 30770324 | Derived | Van de Wijer L, Mchaile DN, de Mast Q, Mmbaga BT, Rommelse NNJ, Duinmaijer A, van der Ven AJAM, Schellekens AFA, Kinabo GD. Neuropsychiatric symptoms in Tanzanian HIV-infected children receiving long-term efavirenz treatment: a multicentre, cross-sectional, observational study. Lancet HIV. 2019 Apr;6(4):e250-e258. doi: 10.1016/S2352-3018(18)30329-1. Epub 2019 Feb 12. |
| ID | Term |
|---|---|
| D002652 | Child Behavior |
| D019954 | Neurobehavioral Manifestations |
| D055118 | Medication Adherence |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| ID | Term |
|---|---|
| D001519 | Behavior |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010349 | Patient Compliance |
| D010342 | Patient Acceptance of Health Care |
| D000074822 | Treatment Adherence and Compliance |
| D015438 | Health Behavior |
| D064419 | Chemically-Induced Disorders |
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| ID | Term |
|---|---|
| C098320 | efavirenz |
| D019829 | Nevirapine |
| C558899 | lopinavir-ritonavir drug combination |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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