Clinical trial NCT03227653: Neuropsychiatric Side Effects of Efavirenz in Children Living With HIV
Official title: Neuropsychiatric Adverse Effects of Efavirenz in Children Living With HIV in Kilimanjaro, Tanzania
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Efavirenz
Child Behavior
Cognitive Symptom
Medication Adherence
Drug-Related Side Effects and Adverse Reactions
Keywords: Efavirenz
Child Behavior
Cognition
Medication Adherence
Drug-Related Side Effects
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Kilimanjaro Christian Medical Centre, Tanzania
name: Kilimanjaro Clinical Research Institute
First posted: 2017-07-24
Enrollment: 144
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Tanzanian children (6-12 years) living with HIV and receiving cART

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.

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. .

Eligibility criteria: 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

Primary outcomes:
measure: Neuropsychological symptoms: competence and psychopathology (internalizing/externalizing symptoms)
timeFrame: At day of inclusion
Secondary outcomes:
measure: Cognitive functioning - non-verbal cognitive ability (general intelligence)
timeFrame: At day of inclusion
measure: Cognitive functioning - working memory
timeFrame: At day of inclusion
measure: Treatment adherence
timeFrame: At day of inclusion
Other outcomes:
measure: Central nervous system symptoms
timeFrame: At day of inclusion
Locations:
city: Moshi
country: Tanzania
facility: Kilimanjaro Christian Medical Centre
state: Kilimanjaro Region
city: Moshi
country: Tanzania
facility: Mawenzi Regional Hospital
state: Kilimanjaro Region
city: Kibosho
country: Tanzania
facility: Kibosho Hospital
city: Moshi
country: Tanzania
facility: Kiboroloni Dispensary
city: Moshi
country: Tanzania
facility: Majengo Health Centre
city: Moshi
country: Tanzania
facility: Pasua Health Centre
Study officials:
affiliation: Kilimanjaro Christian Medical Centre
name: Grace Kinabo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Medical Center
name: André van der Ven, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.