Neuropsychiatric Side Effects of Efavirenz in Children Living With HIV

NCT03227653 | Completed FDA Drug

• 1 other identifier: EFV Kids
• Study Type: observational
• Target: 144
• Locations: 1 country
• Sites: 6

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Cognitive functioning - non-verbal cognitive ability (general intelligence)

  At day of inclusion

• Cognitive functioning - working memory

  At day of inclusion

• Treatment adherence

  At day of inclusion

Other Outcomes (1)

• Central nervous system symptoms

  At day of inclusion

Study Arms (2)

Efavirenz

Children using efavirenz-based cART for at least 6 months

Drug: Efavirenz

Non-efavirenz

Children using non-efavirenz-based cART (nevirapine or Lopinavir-Ritonavir Drug Combination) for at least 6 months.

Drug: Nevirapine; Drug: Lopinavir-Ritonavir Drug Combination

Interventions

Efavirenz DRUG

Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS

Also known as: Efavirenz-group

Efavirenz

Nevirapine DRUG

Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS

Also known as: Non-efavirenz group

Non-efavirenz

Lopinavir-Ritonavir Drug Combination DRUG

Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS

Also known as: Non-efavirenz group

Non-efavirenz

Eligibility Criteria

• Age: 6 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Tanzanian children (6-12 years) living with HIV and receiving cART

You may qualify if:

• 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

You may not qualify if:

• 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
• Children with parent(s) or caregiver(s) not wanting or not able to give informed consent

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Kilimanjaro Christian Medical Centre, Tanzania: collaborator
• Kilimanjaro Clinical Research Institute: collaborator

Study Sites (6)

Kilimanjaro Christian Medical Centre

Moshi, Kilimanjaro, 3010, Tanzania

Location

Mawenzi Regional Hospital

Moshi, Kilimanjaro, 3054, Tanzania

Location

Kibosho Hospital

Kibosho, Tanzania

Location

Kiboroloni Dispensary

Moshi, Tanzania

Location

Majengo Health Centre

Moshi, Tanzania

Location

Pasua Health Centre

Moshi, Tanzania

Location

Related Publications (4)

• 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.

  PMID: 27599655 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.

  PMID: 25808896 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.

  PMID: 29088326 BACKGROUND

• 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.

  PMID: 30770324 DERIVED

MeSH Terms

Conditions

Child Behavior; Neurobehavioral Manifestations; Medication Adherence; Drug-Related Side Effects and Adverse Reactions

Interventions

efavirenz; Nevirapine; lopinavir-ritonavir drug combination

Condition Hierarchy (Ancestors)

Behavior; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Patient Compliance; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Grace Kinabo, MD, PhD

  Kilimanjaro Christian Medical Centre

  PRINCIPAL INVESTIGATOR

• André van der Ven, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2017
• First Posted: July 24, 2017
• Study Start: June 19, 2017
• Primary Completion: December 31, 2017
• Study Completion: December 31, 2017
• Last Updated: July 10, 2018

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

TA (6)