Neuropsychiatric Side Effects of Efavirenz in Children Living With HIV

Completed

• Conditions: Efavirenz; Medication Adherence; Child Behavior; Drug-Related Side Effects and Adverse Reactions; Cognitive Symptom
• Interventions: Drug: Nevirapine; Drug: Efavirenz; Drug: Lopinavir-Ritonavir Drug Combination

• Registration Number: NCT03227653
• Lead Sponsor: Radboud University Medical Center

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. .

Study Timeline

• Study Start: 2017-06-19
• Study First Submitted: 2017-07-18
• Study First Submitted QC: 2017-07-20
• Study First Posted: 2017-07-24
• Primary Completion: 2017-12-31
• Study Completion: 2017-12-31
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-09
• Last Update Posted: 2018-07-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 144

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Non-efavirenz	Lopinavir-Ritonavir Drug Combination	Children using non-efavirenz-based cART (nevirapine or Lopinavir-Ritonavir Drug Combination) for at least 6 months.
Non-efavirenz	Nevirapine	Children using non-efavirenz-based cART (nevirapine or Lopinavir-Ritonavir Drug Combination) for at least 6 months.
Efavirenz	Efavirenz	Children using efavirenz-based cART for at least 6 months

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (6)

Mawenzi Regional Hospital; 🇹🇿 Moshi, Kilimanjaro Region, Tanzania

Kilimanjaro Christian Medical Centre; 🇹🇿 Moshi, Kilimanjaro Region, Tanzania

Kiboroloni Dispensary; 🇹🇿 Moshi, Tanzania

Kibosho Hospital; 🇹🇿 Kibosho, Tanzania

Majengo Health Centre; 🇹🇿 Moshi, Tanzania

Pasua Health Centre; 🇹🇿 Moshi, Tanzania