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Neuropsychiatric Side Effects of Efavirenz in Children Living With HIV

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ClinicalTrials.gov Identifier: NCT03227653
Recruitment Status : Completed
First Posted : July 24, 2017
Last Update Posted : July 10, 2018
Sponsor:
Collaborators:
Kilimanjaro Christian Medical Centre, Tanzania
Kilimanjaro Clinical Research Institute
Information provided by (Responsible Party):
Radboud University

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.


Condition or disease Intervention/treatment
Efavirenz Child Behavior Cognitive Symptom Medication Adherence Drug-Related Side Effects and Adverse Reactions Drug: Efavirenz Drug: Nevirapine Drug: Lopinavir-Ritonavir Drug Combination

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. .

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Study Type : Observational
Actual Enrollment : 144 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Neuropsychiatric Adverse Effects of Efavirenz in Children Living With HIV in Kilimanjaro, Tanzania
Actual Study Start Date : June 19, 2017
Actual Primary Completion Date : December 31, 2017
Actual Study Completion Date : December 31, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Efavirenz

Group/Cohort Intervention/treatment
Efavirenz
Children using efavirenz-based cART for at least 6 months
Drug: Efavirenz
Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS
Other Name: Efavirenz-group

Non-efavirenz
Children using non-efavirenz-based cART (nevirapine or Lopinavir-Ritonavir Drug Combination) for at least 6 months.
Drug: Nevirapine
Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS
Other Name: Non-efavirenz group

Drug: Lopinavir-Ritonavir Drug Combination
Weight-based dosing according to the National Guidelines for the Management of HIV and AIDS
Other Name: Non-efavirenz group




Primary Outcome Measures :
  1. Neuropsychological symptoms: competence and psychopathology (internalizing/externalizing symptoms) [ Time Frame: 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 :
  1. Cognitive functioning - non-verbal cognitive ability (general intelligence) [ Time Frame: At day of inclusion ]
    Non-verbal cognitive ability will be assessed using the Raven's Progressive Matrices

  2. Cognitive functioning - working memory [ Time Frame: At day of inclusion ]
    Working memory will be assessed using the Wechsler Intelligence Scale for Children (WISC-III) Digit Span Test

  3. Treatment adherence [ Time Frame: 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)


Other Outcome Measures:
  1. Central nervous system symptoms [ Time Frame: At day of inclusion ]
    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.



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Ages Eligible for Study:   6 Years to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Tanzanian children (6-12 years) living with HIV and receiving cART
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03227653


Locations
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Tanzania
Kilimanjaro Christian Medical Centre
Moshi, Kilimanjaro Region, Tanzania, 3010
Mawenzi Regional Hospital
Moshi, Kilimanjaro Region, Tanzania, 3054
Kibosho Hospital
Kibosho, Tanzania
Kiboroloni Dispensary
Moshi, Tanzania
Majengo Health Centre
Moshi, Tanzania
Pasua Health Centre
Moshi, Tanzania
Sponsors and Collaborators
Radboud University
Kilimanjaro Christian Medical Centre, Tanzania
Kilimanjaro Clinical Research Institute
Investigators
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Principal Investigator: Grace Kinabo, MD, PhD Kilimanjaro Christian Medical Centre
Principal Investigator: André van der Ven, MD, PhD Radboud University

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT03227653     History of Changes
Other Study ID Numbers: EFV Kids
First Posted: July 24, 2017    Key Record Dates
Last Update Posted: July 10, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Radboud University:
Efavirenz
Child Behavior
Cognition
Medication Adherence
Drug-Related Side Effects
Additional relevant MeSH terms:
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Neurobehavioral Manifestations
Drug-Related Side Effects and Adverse Reactions
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Chemically-Induced Disorders
Ritonavir
Lopinavir
Nevirapine
Efavirenz
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers