Neurodevelopmental Problems

in HIV-infected Children
Endah Citraresmi
HIV Task Force, Indonesia Pediatric Society
Harapan Kita Women & Children Hospital, Jakarta
Outline

Normal Neurodevelopmental
HIV in children development in problems in HIV-
children infected children

Neurodevelopmental
screening in HIV- Summary
infected children
HIV in Children
HIV affects an estimated 3.2 million children worldwide, and the
majority of the 240,000 newly infected children are perinatally HIV
(PHIV)-infected
The virus can enter the central nervous system (CNS) within days after
primary infection, posing a major threat to neurodevelopment

Global Update on the Health Sector Response to HIV. Geneva: WHO; 2014
J Infect Dis. 2012;206(2):275282
HIV in Children
Children infected with HIV are at increased risk for CNS disease
characterized by cognitive, language, motor, and behavioral
impairments.
The severity: ranges from subtle impairments in selective domain to
severe deterioration of global developmental skills
HIV-related CNS dysfunction in children is primarily the result of HIV
infection in the brain

J. Infect.Dis. 174 : 6 (1996), 12006.

Neurodevelopmental Problems in HIV Children
Early in the epidemic, 50-90% of children with HIV-1 infection
exhibited severe CNS manifestations = HIV encephalopathy
More recent studies: prevalence of encephalopathy in HIV infected
children 13-23%
This decline may be related in part to the earlier and more generalized use of
combination antiretroviral treatment (ART), including HAART
HAART: effective in suppressing systemic viral replication reduce
the number of HIV-infected cells entering the CNS
Many antiretroviral agents do not penetrate well into the CNS well-
controlled systemic disease may still be at risk for developing CNS
manifestations
Am. J. Dis. Child. 142,1988;1:2935
Pediatrics, 1986;78:67887
Neurology, 2000;54:108995
Normal Development

Development occurs with sequential acquisition of skills in four

different areas
Gross Motor
Fine Motor
Language
Psychosocial
Language development most approximates cognition
Normal Development Principles
Development is a continuous process
The sequence is the same but the rate
varies between children
The sequence is set in each field, but
each field is not necessarily parallel
Development is related to the rate of
maturation of the CNS
No strict line between normal and
abnormal
Developmental Delay
Normal progress

rapid progress needed

to catch up

Delay
Developmental Delay in HIV Children
Virus

Antiretroviral Developmental delay in HIV Prematurity

treatment children

Environmental factors

Reduced Multiple stresses Caretaker

stimulation changes

Poverty Parental risks: alcohol, drug use, Family illness Stigma, hospitalisation,
mental health disorders separation, rejection
HIV-Encephalopathy
HIVE refers to the disease, damage or malfunction of the brain caused
by HIV-1.
Static HIVE is an unchanging, less threatening type of encephalopathy,
whereas,
Progressive HIVE gradually becomes more destructive over time.
Currently, HIVE is classified as a stage 4 AIDS-defining illness (WHO)
reflecting the severity of the disease
HIV-encephalopathy diagnostic criteria

One or more of the following criteria must be met:

Loss of previously-acquired skills
Significant drop in cognitive test scores, generally to the borderline/delayed range with
functional deficits (deficits in day-to-day functioning)
Cognitive test scores are in the borderline/delayed range with functional deficits (and no
history of significant drop or previous testing available)
Significantly abnormal neurologic exam with functional deficits (i.e. significant tone, reflex,
cerebellar, gait, or movement abnormalities)
Significant improvement in cognitive test scores over approximately a 6-month period
associated with a new treatment when baseline scores are in the borderline to delayed
range (no history of previous testing) with or without significant brain imaging or
neurologic abnormalities (retrospective classification)

Textbook of Pediatric HIV Care; 2004

 Pediatric AIDS, 3rd Ed 1998:293-308
Clinical Course
of HIV
Encephalopathy
Subacute: Children exhibit a loss of
previously acquired skills, resulting in a
significant decline in raw and standard score
on psychometric tests, and new neurologic
abnormalities
Plateau: Children either do not gain further skills or
exhibit a slowed rate of development compared
with their previous rate of development, resulting
in a significant drop in standard scores on
psychometric tests
Static: Children exhibit consistent but slower than
normal development in the delayed range or their
neuropsychological functioning remains stable for at
least 1 year after a significant decline (IQ scores
remain below average and without significant
decline for at least 1 year)
Motor development impairment

Pre-PI introduction After PI introduction

Pediatrics. 2007;119(3):e681e693
Loss of motor function is less evident in older children, but subtle strength
and fine-motor impairments have been reported in clinically stable school-
age PHIV-infected children, both cART-nave and -experienced

Pediatrics 2005;115:380387
Clin Infect Dis. 2012;54(7):10011009
Percentage of infants delayed at each
visit for developmental outcomes.

AIDS Care, 2014;26:497504

Intelligence quotient (IQ) comparison between the HIV-infected
children and the HIV-uninfected control group children

Pediatr Infect Dis J . 2013; 32: 5018

 Neurodevelopmental outcomes
Neuro Cognitive Function (Full scale IQ)

100
90
83 83 86
80
78 75
Mean IQ Score
60

40

20

CDC C HIV HEU HIV HEU Control

PHACS ( N =558) Thai-PREDICT (N =603)
Mean age 12 years Mean age 9 years
Smith R. Pediatr Infect Dis J 2012;31:592-8. Puthanakit T. Pediatr Infect Dis 2013; 32:501-8.
Antiretroviral Treatment
Antiretroviral treatment has been proven to prolong survival rates of
children suffering from HIV/AIDS by promoting normal growth and
development
ART has dramatically decreased the rate of HIVE in the United States
from 35-50% to less than 2%
Recent studies of children treated with a HAART regimen containing a
protease inhibitor all indicated normal global cognition mean scores
As with earlier studies, subtle significant differences were noted in executive
function, verbal skills, behavior, and memory

Pediatrics 2008;122:e123-8
Pediatrics 2012;130:e132644
 List of the neurobehavioral
functions to be assessed and
psychometric tests that can be
used as part of a comprehensive
psychological assessment of
children with HIV infection
 Recommended neurodevelopmental serial
assessment schedule for children with HIV-1 infection
at various ages

Age of child Serial assessment schedule

< 2 year Evaluate every 6 months due to a higher
risk of developing CNS disease
2-8 years Evaluate every year unless they exhibit
neurodevelopmental deficits, in which
case they should be assessed every
6 months
>8 years Evaluate every 2 years if child exhibits
stable functioning in the average range;
otherwise, evaluate every year

*Shorter batteries of individual subtests and specific function tests can be

administered between the major evaluations to further decrease the testing
burden on children while still monitoring the effects of the disease
Kuesioner Pra Skrining Perkembangan

9-10 pertanyaan singkat pada orangtua/pengasuh

Umur 3 bulan 6 tahun (setiap 3-6 bulan)
Metode sederhana untuk mendeteksi adanya
gangguan perkembangan
Interpretasi:
jawaban ya < 7 mungkin ada gangguan
ya 7 8 periksa ulang 1 minggu kemudian
ya > 9 umumnya tidak ada gangguan

Untuk anak >6 tahun?

Masalah mental: Pediatric symptom check list
Kognitif: Tes IQ
Neurodevelopmental problems in HIV
children
Neurobehavioural assessment need to be performed routinely:
0-6 years
>6 years? What tools?
Need multidiscipline approach: HIV practitioner, pediatric
neurology/growth & development consultant, psychologist, medical
rehabilitation practitioner, etc
Findings from psychometric testing are useful for planning
appropriate individual educational, rehabilitative, and psychosocial
interventions
Summary
Children infected with HIV are at increased risk for CNS disease
characterized by cognitive, language, motor, and behavioral
impairments
The severity: ranges from subtle impairments in selective domain to
severe deterioration of global developmental skills
Regular psychometric testing can identify early neurobehavioral
changes in functioning
Findings from psychometric testing are useful for planning
appropriate individual educational, rehabilitative, and psychosocial
interventions