Neuropsychiatric Side Effects of Efavirenz in Children Living With HIV

Medication Adherence Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03227653
• Other study ID #: EFV Kids
• Status: Completed
• Start date: June 19, 2017
• Est. completion date: December 31, 2017

Study information

• Verified date: July 2018
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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. .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 144
• Est. completion date: December 31, 2017
• Est. primary completion date: December 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 12 Years

Eligibility

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

Related Conditions & MeSH terms

• Child Behavior
• Cognitive Symptom
• Drug-Related Side Effects and Adverse Reactions
• Efavirenz
• Medication Adherence
• Neurobehavioral Manifestations

Intervention

Drug:
• Efavirenz
Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS
• Nevirapine
Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS
• Lopinavir-Ritonavir Drug Combination
Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS

Locations

Country	Name	City	State
Tanzania	Kibosho Hospital	Kibosho
Tanzania	Kiboroloni Dispensary	Moshi
Tanzania	Kilimanjaro Christian Medical Centre	Moshi	Kilimanjaro Region
Tanzania	Majengo Health Centre	Moshi
Tanzania	Mawenzi Regional Hospital	Moshi	Kilimanjaro Region
Tanzania	Pasua Health Centre	Moshi

Sponsors (3)

Lead Sponsor	Collaborator
Radboud University	Kilimanjaro Christian Medical Centre, Tanzania, Kilimanjaro Clinical Research Institute

Country where clinical trial is conducted

Tanzania, 

References & Publications (3)

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. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	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
Secondary	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
Secondary	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