Transcript 10478 KB - I-TECH

Pediatric HIV/AIDS
Courtesy of:
International Center for AIDS Care and
Treatment Programs
Columbia University
Mailman School of Public Health
Overview
Learning Objectives:
Overview and Challenges
 Describe the scope of the pediatric HIV/AIDS
epidemic in Sub-Saharan Africa and Ethiopia
 List the special challenges in the care of children
with HIV/AIDS
 Discuss ways to overcome these challenges
3
Historical Perspective of Pediatric HIV:
Sub-Saharan Africa
 1983-1985 the first cases of pediatric HIV were
first observed in Rwanda, the Democratic
Republic of Congo, and Uganda
 Mid 1980’s longitudinal cohort studies started in
East Africa (Kigali, Kampala, Kinshasha, Nairobi)
to study maternal to child transmission and the
natural history of HIV-exposed and infected
children
 In 1988 the first specialist clinic started in
Uganda
4
Estimated Number of Children <15 Years
Living with HIV/AIDS at the End of 2005
Western & Central
Europe
North America
11 000
6 200
[4 900 – 7 900]
Eastern Europe
& Central Asia
8 800
[7 100 – 13 000]
East Asia
[5 600 – 17 300]
Caribbean
23 000
[12 000 – 49 000]
Latin America
26 000
[21 000 – 43 000]
9 400
North Africa & Middle East
24 000
[7 100 – 82 000]
Sub-Saharan
Africa
Sub-Saharan
Africa
million
2.31.9
million
[1.7 –million]
2.3 million]
[2..1-2.8
[3 300 – 27 000]
South
& South-East Asia
170 000
[95 000 – 320 000]
Oceania
700
[< 2 500]
Estimated Number of Children (<15 years)
Newly Infected with HIV During 2005
Western & Central
Europe
North America
< 100
< 100
Caribbean
6 100
[3 100 – 13 000]
Latin America
6 800
[5 400 – 11 000]
Eastern Europe
& Central Asia
1 800
[1 200 – 3 700]
North Africa & Middle East
9 100
[2 800 – 30 000]
Sub-Saharan
Africa
560 000
[500 000 – 650 000]
East Asia
4 100
[1 500 – 11 000]
South
& South-East Asia
51 000
[30 000 – 95 000]
Oceania
< 300
[< 1 000]
Children Born with HIV
 In 2003, there were an
estimated 128,000
pregnancies among HIVinfected women in
Ethiopia
 At least 35,000 infants
were born with HIV
7
Pediatric HIV/AIDS in Ethiopia
 More than 122,00 children under the age of 15
are living with HIV/AIDS in Ethiopia
 63,000 are in immediate need of ART
 Only 1200 are on ART ~1.9%
 Over 29,000 people receiving ART in Ethiopia,
however only 4% are children
8
BARRIERS TO CARE
 Why is care for infants and children difficult?
 Technical barriers in low-resource settings
 Disease progression is especially rapid in children
 Marginal political/community commitment to a
pediatric agenda
9
BARRIERS TO CARE: Technical
Barriers
 Diagnostic challenges
 Identification, virologic testing of infants <18 months, stigma,
consent, etc)
 Complexity of ART administration
 Procurement of pediatric formulations
 Weight-based dosing
 Pediatric adherence
 Infrastructure & human resource requirements
 PMTCT follow up
 Systems for chronic care (appointments, medical records,
community outreach)
 Training
10
Success Stories
 Dramatic improvements in morbidity and
mortality have been seen in high resource
settings secondary to:




Accessible pediatric health services
Widespread use of OI prophylaxis (cotrimoxazole)
Access to antiretroviral therapy
Successful perinatal prevention
 Care and treatment is also feasible in resource
limited settings
11
Response to ART among children in the
MTCT-Plus Initiative
 Mean increase in CD4 of
431 cells/6 mo
 Mean increase in CD4%
of 10.5%
 In age-stratified analysis,
response was best in
children in whom ART
was initiated at < 12 mo
of age
60.00
CD4+ percent (%)
50.00
40.00
30.00
20.00
10.00
0.00
-20
0
20
40
60
80
100
Time since ART initiation (weeks)
120
Abrams et al. IAS 2005,
abstract # MoPe11.6C28
12
Pediatric Care and Treatment
 Maximize interventions for PMTCT
 Enhance care and treatment for HIV-infected
and HIV-exposed infants
 Engage women and their families in
comprehensive care and treatment
13
Pediatric Care and Treatment (2)
 Increase availability of infant diagnostics
 Enhance case finding and referral
 Ensure follow up and comprehensive care and
treatment
 Increase availability of and access to pediatric
ART
14
Care of the
HIV-Exposed Infant
Learning Objectives:
Care of the HIV-Exposed Infant
 Understand the distinction between HIVexposed and HIV-infected infants
 Recognize the goals of care for HIV-exposed
infants
 Understand routine care procedures for HIVexposed infants
16
Challenges to Care
 Disease Transmission: antepartum, intrapartum,
or postpartum (through breast feeding)
 Testing: All exposed infants (infected and noninfected) will test antibody positive during the
first few months of life
 Exclusion: While the child with HIV infection can
often be identified during the first months of life,
HIV infection often cannot be excluded until after
1 year of age, particularly in breast fed babies
17
Challenges to Care (2)
 Disease Progression: rapid progression in
pediatric cases and often requires treatment
before a positive diagnosis can be confirmed
 Opportunistic Infections: HIV-infected infants
are susceptible PCP, TB, and bacterial infections
that are associated with high rates of infant
mortality
18
Clinical Objectives
 Close monitoring of HIV-exposed infants
 for rapid disease progression and failing health status
 Use of prophylaxis in HIV-exposed infants
 to prevent opportunistic infections
 Early identification and treatment
 of HIV-infected infants
19
Background: Pediatric HIV Disease
 Infancy and early childhood is a time of rapid HIV
disease progression
 Most children die before a diagnosis of HIV is made
 Common causes of morbidity and mortality in children





Growth failure
Tuberculosis
PCP
HIV encephalopathy
Bacterial infections/pneumonia
20
Components of Clinical Care
for the HIV-Exposed Infant
 History (birth, interim history, and parental
concerns)
 Physical exam
 Growth and nutrition evaluation
 Developmental assessment
 Cotrimoxazole preventative therapy
 Determination & evaluation of infection status
 Assessment and plan
21
Clinical Care: History
 Birth-Identify children at higher risk of
transmission/infection and higher risk of rapid
progression
 Parents should be given the opportunity to
communicate anxieties and problems as they
will be the first to recognize them
 At each visit ask:
 Has the child been ill? How is the child eating? Any
new accomplishments? Has anyone in the household
been diagnosed or developed symptoms of
tuberculosis? Any new medications?
22
Clinical Care: Physical Exam
 Monitor growth rate:
 Infected infants generally grow more slowly than
uninfected infants.
 Growth can be the most sensitive clinical indication of
HIV infection in an infant/young child and needs to be
monitored closely for all exposed infants
 Monitor disease progression:
 Infected infants have a high frequency of HIV related
morbidities due to rapid disease progression.
Example: fever, oral thrush, skin rashes,
hepatomegaly, splenomegaly, lymphadenopathy,
weakness, muscle wasting, encephalopathy, etc.
23
Clinical Care: Growth and Nutrition
 Growth Chart: What is it?
 Growth data collected from large numbers of children
in a particular population.
 Normative data on weight, height and head
circumference by age and sex
 Why use it?
 Easy and systematic way to follow changes in growth
over time for an individual child
 Easy to plot measurements at regular intervals
• Monthly for all infants
• Quarterly for older HIV-infected children
24
Growth Chart/Curve
 Use WHO growth curves
or CDC growth curves
 The choice of growth
chart is less important
than following the growth
of an individual child
along their own curve on
a chart
25
WHO Growth Curves
 WHO growth curves are
 Age and gender specific
 Extend from birth to 5 years
•
•
•
•
Weight for age: boys and girls
Height/length for age: boys and girls
Weight for height/length: boys and girls
BMI for age: boys and girls
 Use WHO Growth Curves to monitor growth of
boys and girls, birth to 5 years
26
WHO Child Growth Curves
27
CDC Growth Curves
 CDC growth curves are
 Age and gender specific
 Extend from birth to 20 years
•
•
•
•
•
Weight for age: boys and girls
Height/length for age: boys and girls
Head circumference for age: boys and girls
Weight for height/length: boys and girls
BMI for age: boys and girls
 Use CDC Growth Curves to monitor:
 Growth of boys and girls, > 6 years
 Head circumference for boys and girls < 3 years
28
How to Use and Interpret
a Growth Curve
 Measure and weigh child using same
methodology at each visit
 Use a GROWTH CURVE for weight, height, and head
circumference plotted EVERY MONTH
 Using age and sex appropriate charts, plot
measurement (weight, height, head
circumference) on the vertical against age on
the horizontal axis
 Compare growth point with previous points
 Assess growth percentile
29
Weight for Age
The child weighs 6kg
The child is in the 15th percentile of weight for age
He is 4 months old
30
Head circumference is 38 cm
Head circumference for age
Age is 3 months
95
90
75
50
25
10
5
The head circumference is below the 5th percentile for age
This child is microcephalic
31
Clinical Care: Growth and Nutrition
 Nutrition:




Assess mode of feeding
frequency (duration or ounces)
adequacy of supply
bowel habits, reported problems
 Infant feeding practices
32
Infant Feeding Practices
 Mixed feeding may increase the infant’s chance
of becoming HIV infected during the period of
breastfeeding
 For HIV infected mothers choosing to
breastfeed, WHO recommends exclusive
breastfeeding for 6 months
33
Breast Feeding
Advantages
 Promotes closeness between
mother and infant
 Protective maternal antibodies
 Does not depend on
availability of formula or clean
water
 Societal norm
 Exclusive breast feeding may
not increase the risk of MTCT
 Does not impact maternal
health status
Disadvantages
 Risk of HIV transmission to the
infant
 If maternal health is poor,
maternal milk may not be
complete in nutrients
34
Formula Feeding
Advantages
 Decreased risk of PMTCT
 Baby can be fed by other
family members
 Feeding from a bottle or
cup requires less work for
the infant
 Nutritionally complete
(doesn’t depend on
mother’s health)
Disadvantages
 Costly and not readily
available in many settings
 Not societal norm in
many settings
 No maternal antibodies
 Need clean water, clean
supplies
 Need supplies on hand
when not at home
35
Summary: Infant Feeding
 Choosing to breast feed or formula feed is complex:
 Personal preference of woman/family
 Local community norms
 Availability of supplies (formula, water)
 Counseling should be provided re: risks and benefits
 Women should be supported in their decisions about
feeding choices
 Infant feeding should be discussed at each visit for
mother and child
 Assure accurate history of intake
 Assess problems and concerns
36
Clinical Care: Developmental Assessment
 Delayed/abnormal development or loss of
milestones may be the first sign of HIV infection
in infants that raise concerns
 Abnormal development can be caused by other
factors
 Infants are at high risk for HIV encephalopathy
37
Clinical Care:
Developmental Assessment (2)
 A developmental assessment that includes the
following should be conducted at each visit:




Cognitive, motor, language, and social skills
Discuss the infant’s milestones
Verify appropriate development for age
Use a developmental check list or observe the infant
during the examination
38
Clinical Care:
Developmental Assessment (3)
 Developmental Checklist may include:
 1 month: raises head, crawling movement, alerts to
sound
 2 months: head midline, lifts chest off table, smiles
socially
 4 months: rolls front to back, laughs
 6 months: sits unsupported, babbles
 9 months: pulls to stand, says “mama”
 12 months: walks alone, two words
39
Clinical Care: Cotrimoxazole Preventive
Therapy
 HIV infected infants are at high risk for acquiring pneumocystis
jiroveci pneumonia (PCP), a rapidly progressive pneumonia
 Severe and rapidly progressive pneumonia




Tachypnea
Hypoxia
Diffuse interstitial pneumonitis
High risk of death
 Occurs early, often before child is identified as HIV-infected
 Peak incidence is between 3-6 months
 Diagnosis difficult and invasive measures are often necessary
(tracheal aspirate, induced sputum, BAL)
 Risk can be reduced with routine use of cotrimoxazole
40
Clinical Care: Cotrimoxazole Preventive
Therapy (2)
 The most common OI in children in the US was
PCP with the peak incidence is at 3-6 months of
life
 Can also occur in older children with severe
immune compromise
 Introduction of routine prophylaxis for all HIVexposed, coupled with effective perinatal
prevention resulted in a drastic reduction in PCP
in the US
41
Diagnosis of PCP in HIV-Infected Children
with Respiratory Disease
60
% PCP
50
40
30
20
10
0
Capetown
Bangkok
Soweto
Lusaka
42
Clinical Care: Cotrimoxazole Preventive
Therapy (3)
 Given to all HIV-exposed and infected infants 112 months
 PCP prophylaxis for HIV-exposed infants
 Until the child is no longer breast-feeding and is
determined to be uninfected or
 After two negative virologic tests, with one ≥ 4
months, in clinically well, exclusively formula-fed
infants
43
CPT Dosing Recommendations
Trimethoprim/sulfamethoxazole
CTX/SMZ, Cotrimoxazole, Septrim®, Bactrim®
weight in kilograms
8mg/ml suspension single-strength tablet
(daily dose in milliliters)
(80 mg TMP/400 mg SMZ)
3 – 4.9 kg
2 ml daily
5 – 6.9 kg
3 ml daily
7 – 9.9 kg
4 ml daily
½ single-strength tab daily
10 – 11.9 kg
5 ml daily
½ single-strength tab daily
12 – 14.9 kg
7 ml daily
1 single-strength tab daily
15 – 16.9 kg
8 ml daily
1 single-strength tab daily
17 – 19.9 kg
9 ml daily
1 single-strength tab daily
20 – 24.9 kg
11 ml daily
1 single-strength tab daily
25 – 29.9 kg
14 ml daily
2 single-strength tabs* daily
30 – 34.9 kg
17 ml daily
2 single-strength tabs* daily
35 – 40 kg
20 ml daily
2 single-strength tabs* daily44
*or one double strength tab
Clinical Care: Immunizations
 Immunize infants early before there is damage
to the immune system
 Routine immunizations per local guidelines
 Do not give BCG to any symptomatic infant
45
Clinical Care: Determining Infection Status
 Priority to determine infected babies who need care and
treatment rather than confirm the absence of disease
 All HIV exposed infants should have virologic testing
early, between 6-12 weeks of age
 Interpretation should be done in the context of the
clinical presentation of the infant
 Antibody test is used in children >12 months of age
 If virologic tests are not available, WHO recommends
presumptive clinical diagnosis of severe HIV in infants
<18 months of age
 Breastfed infants with initial negative virologic tests
should continue to be evaluated for clinical evidence of
HIV infection
46
Follow-up Schedule for the
HIV-exposed Infant
 Basic principles:
 Early identification of infants who are sick or failing to
thrive is critical
 Careful and frequent clinical monitoring is required
 Systematic follow up is vital
• Appointment systems
• Medical records
• Family education and support
47
Follow-up Schedule for the
HIV-exposed Infant
Visit Schedule
Monthly visits for the first 6 months, then every three months until HIV infection status determined
4-6 weeks 3 months
5 months
6 months
2 months
4 months
9 months
15 months
12 months
18 months
Virologic test
HIV antibody testing
12 months
Follow-up schedule can be modified per local and national guidelines.
48
Clinical Care: Assessment and Plan




What is the child’s HIV status?
Does the child have any new problems?
Does the child require any laboratory studies?
Has the child received proper vaccinations?
Medications? OI Prophylaxis?
 When should the child return to clinic?
49
Case Study: Yared
 Yared is a 3 month-old male who is brought in for his
monthly check up
 Baby is breastfeeding at night, but is fed porridge during
the day by Grandma, who does not know of mom’s
status
 Lately the baby has been feeding poorly. He has had
diarrhea for the past two days
 Mom notes that she thinks he isn’t growing as well
 Yared receives cotrimoxazole, but sometimes he misses
a dose when Grandma is caring for him, since she does
not know that he takes this
50
Case Study: Yared (2)
 Yared’s physical exam is significant for




Bilateral cervical and axillary nodes
Notable cough
Diarrhea x2 during the exam
Depressed developmental stage
 His growth has slowed
 The last time Yared was seen in the clinic, the
PCR machine was broken so he has not had
any virologic testing done
51
52
Case Study: Yared (3)
 Is there evidence of HIV infection?
 Are there other problems or concerns?
 What else should be done at this visit?
53
Case Study: Yared (4)






Poor growth, adenopathy and diarrhea
Findings consistent with HIV infection
Cough probably URI
He is at risk for development of PCP
Situation complicated by feeding change
Need to assess family situation
54
Case Study: Yared (5)
 Review cotrimoxazole medication and
importance of adherence
 Labs: FBC, DNA-PCR, CXR
 Stool sample
 Complete nutritional assessment
 Evaluation of cough including history of TB
exposure
 Psychosocial support, including adherence and
nutritional support for mother
55
Case Study: Yared (6)
 The chest X-ray is normal
 Results of the FBC will not be ready until
tomorrow
 Mother sees the nutritionist and the counselor
before leaving the clinic
56
Case Study: Yared (7)
 Yared returns in 2 weeks for his results
 HIV DNA PCR is positive
 Yared is diagnosed with HIV infection
 Send a repeat DNA PCR for confirmation
 Yared is referred for staging and initiation of ART
at the local hospital
57
Family Health and Well Being
 Families benefit from open and honest
exchange of information about the child
 Use simple language to explain the difference
between exposure to HIV and HIV infection
 Make sure to repeat the information at each visit
 All family members (infected and non-infected)
can benefit from psychosocial support
58
Role of the Multi-Disciplinary Team
 Ongoing communication between the members
of the MDT is crucial for supporting the family
and caring for the exposed infant
 Each member of the team will have a different
perspective and different pieces of information
about the family and infant
 Engaging parents in care and treatment can
help to decrease the burden of disease, prevent
orphaning, and keep families healthy
59
Summary
 HIV exposed infants are at risk for HIV infection and rapidly
progressive disease. It is important for providers to:
 Identify the infected children early
 Manage and prevent opportunistic infections
 Maintain and support healthy families
 Exposed infants need to be monitored closely:







History
Physical exam
Nutrition and growth
Developmental assessment
OI prophylaxis
Determination & evaluation of infection status
Assessment and plan for follow up
 All members of the MDT are crucial in supporting the family and
providing comprehensive care for the child
60
Infant Diagnosis
Learning Objectives
 Outline key concepts in diagnosing HIV in
infants
 Review algorithms for diagnosing HIV
 Discuss virologic and antibody tests
 Understand clinical diagnosis
 Review roles of the parent and multidisciplinary
team
62
Complexities of Infant Diagnosis
 Difficult to diagnose
 Routine antibody tests cannot be used
 Specialized virologic tests are necessary
 HIV infection is difficult to exclude
 Infants who breast feed continue to be at risk for
acquiring HIV infection
63
HIV Antibody Testing
 HIV antibody is not used for diagnosis during the
first 12 months of life
 Maternal HIV antibody (IgG) is transferred
across the placenta during pregnancy
 All infants born to HIV+ mothers will test HIV
antibody positive
 HIV antibody fades during first 9 - 18 months of
life in uninfected infants
64
Specialized Virologic Tests
 Specialized virologic tests must be used




HIV DNA PCR
HIV RNA PCR
p24 Antigen
Viral Culture
 Two positive virologic tests = HIV infection
 One positive virologic test = Presumed HIV
infection
65
Specialized Virologic Tests (2)
 HIV DNA & RNA PCR
 Sensitivity (true negatives) increases during first
weeks of life
 Sensitivity can vary with assay and laboratory; assay
should be appropriate for viral subtype
 Theoretically, sensitivity and specificity (true positives)
may vary in populations of infants receiving perinatal
prevention regimens; no supportive data has been
published
66
Specialized Virologic Testing
 Breast-fed infants
 Remain at risk for acquiring HIV infection
 Most are infected in utero, intrapartum and early
postpartum (by 6 weeks of age)
 A negative virologic test cannot reliably exclude HIV
 Must always be tested again 6-12 weeks after
cessation of breast feeding
67
Diagnosing HIV Infection in Children <18
months: When Virologic Tests are Available
 HIV-exposed infants should have virologic
testing early, between 6-8 weeks of age
 DNA PCR & RNA PCR are most widely available
tests for infant diagnosis
 Interpretation of virologic test results should
ALWAYS be done in the context of the clinical
presentation of the infant
 Virologic testing is used primarily to identify the
infected child, not to exclude infection in the
exposed child
68
Early Virologic Testing
 Positive Results
 Indicate HIV infection
 A repeat virologic test should be done to confirm
 Treatment should not be withheld awaiting
confirmation if the infant is symptomatic and/or rapidly
progressing
 Negative Results
69
Early Virologic Testing (2)
 Asymptomatic infant
 Early negative virologic test generally implies that the child is not
infected
 Most children remain at risk for acquiring HIV through
breastfeeding
 Testing with the HIV antibody test should be done at ≥12 months
or >6-12 weeks after the cessation of breastfeeding (whichever
comes later)
 Symptomatic infant
 Repeat virologic testing
 Use CD4 and clinical judgment. Consider starting treatment
depending on disease progression
70
Diagnosing HIV Infection in Children <18
months: Virologic Tests are not Available
 A presumptive diagnosis of HIV infection must
be made based on clinical findings
 Good clinical reasoning can identify children at high
risk for HIV disease & rapid progression
 The purpose of making a presumptive diagnosis
is to initiate ART in the sick child
 Infants with severe manifestations of HIV infection
should not be denied treatment because their
diagnosis cannot be confirmed
71
Presumptive Diagnosis of Severe HIV
Disease in Children <18 months
 HIV antibody positive and
 Diagnosis of Stage 4 or AIDS-indicator condition(s)

OR
 Symptomatic with ≥ 2 of the following:
• Oral thrush
• Severe pneumonia
• Severe sepsis
 Supporting factors
 Recent maternal death
 Advanced HIV disease in the mother
 CD4% < 20% in infant
 The diagnosis should be confirmed with HIV antibody
when the child reaches 18 months
72
Clinical Judgment
 Clinical judgment should guide:
 Interpretation of lab results
• Are results valid? Do the results make sense given the
child’s health? Is the lab trustworthy? Could there be a
specimen mix-up?
 When to repeat PCR testing
• Are the child’s symptoms consistent with HIV infection?
 The decision to consider a child HIV-infected
 The decision to initiate ART
73
Discordance
 Clinical findings may suggest the diagnosis of
HIV infection even when virologic tests are
negative
 Use CD4 to assess immunologic status
• Low CD4 is consistent with HIV diagnosis
 Other diseases can have similar manifestations
and should be ruled out if possible
 Repeat virologic testing should be considered
 HIV antibody testing should be repeated at >18
months to confirm infection status
74
Diagnosing a Child Who Presents at 9-18
Months of Age
 Asymptomatic child
 Screen with HIV antibody
 If positive, virologic testing is indicated
 If negative, no virologic testing is necessary
• If breast feeding, repeat antibody testing >6-12 weeks
after cessation of breast feeding
 Symptomatic child
 Screen with virologic testing
75
Diagnosing HIV in the Child >18 Months
 HIV antibody should be used to diagnose HIV
infection in children >18 months of age
 Children >18 months with positive antibody test
have HIV infection
 A positive antibody test should be confirmed by
duplicate testing
 A negative antibody test in children >18 months
excludes HIV infection
 Except in cases of continued breast feeding.
Antibody should be repeated 6-12 weeks post
cessation of breast feeding
76
Multidisciplinary Team
 Provide ongoing education, support, and
counseling to parent
 Identify problems and issues EARLY
 Form a bridge between parent and medical
provider
 Provide adherence support for both mother and
infant
 Introduce concept of infant diagnostic testing as
part of PMTCT program
77
Multidisciplinary Team (2)
 Support the decision to have early infant
diagnostic testing
 Review results of virologic test
 Explain implications
 Explore parental understanding
 Explore parental concerns
 Review infant feeding decisions
 Emphasize need for ongoing care and treatment
as determined by results
78
Role of the Parent
 Parent needs to understand:
 That infant diagnosis is an ongoing process
 The importance of early testing, frequent monitoring,
and adherence to care
 Often the first to notice signs and symptoms
 Often has multiple complex roles and needs,
including self-care, caretaker role for other
family members, feelings about transmission of
HIV to the infant
 Parent needs understanding and support
79
Case Study: Meseret
 6 week old infant, Meseret, is brought to clinic
for her first post-partum visit
 Mom delivered in a village outside of the city
where her mother and sister still live
 She just returned home with Meseret and her 4
year old son
 Mom was enrolled in a PMTCT program during
pregnancy
 What would you like to know about the baby and
his family?
80
Case Study: Meseret (2)
 Meseret was born at home without problems
 Mother doesn’t know birth weight, but brought
Meseret to health station at 4 days of age,
weighing 2.9 kg
 Mom took her SD-NVP, but the baby didn’t
receive any medication. Mom didn’t tell anyone
at home about her status
 Breast feeding primarily but left the baby with
her sisters on two occasions. During that time
Meseret was fed water and maybe some milk
81
Case Study: Meseret (3)
 Dad is away working. Mom has not disclosed
her HIV status to him
 He comes home 1X/month and gives her money
but she must work in the fields and sells produce
to have enough money
 She uses the general water tap in the
neighborhood
 No running water in the house
 What will you do next?
 What is usually done at a baby’s first visit?
82
Case Study: Meseret (4)—Pertinent
Physical Exam
 Physical examination is remarkable for fairly
extensive oral thrush, and diffuse
lymphadenopathy
 The baby looks a little scrawny and seems
irritable
 What is your assessment of the child?
 What could be causing Meseret’s poor growth?
83
Case Study: Meseret (5)—Pertinent
Physical Exam Growth Chart Infant Girl
95%
90%
75%
50%
25%
10%
5%
Birth Weight- 2.9
kg
Weight at 6 wks3.4 kg
84
Case Study: Clinical Questions
 Physical examination is remarkable for fairly
extensive oral thrush, and diffuse
lymphadenopathy
 The baby looks a little scrawny and seems
irritable
85
Case Study: Meseret (6)
 Mom reports that the baby has not been feeding well for
several days
 You watch the child feed but she tires quickly and falls
asleep. Mom says that this is what has been happening
over the last several days
 She also reports occasional watery stools
 She says that she had a ‘TB’ test at ANC and it was
negative
 Her mother (the child’s grandmother) seemed to be
coughing and had lost some weight, but she didn’t seem
to be too sick
86
Case Study: Meseret (7)
 You send blood for HIV DNA PCR
 You work with mom around enhancing feeding and
arrange for the family to receive food packages
 You prescribe nystatin for the oral thrush
 The child also begins cotrimoxazole prophylaxis
 Mom is instructed to come back in one week to check
the baby again
 Mom does not make the appointment the following week.
 What will the team do to address this missed visit?
87
Case Study: Meseret (8)—MDT
 The case is discussed at the weekly
multidisciplinary meeting and it is decided that
the mom should be contacted immediately. Her
cell number is no longer connected so the
decision is made to make a home visit
 A peer educator and a counselor travel to the
listed address. Mom is not at home but they find
the baby with a neighbor. Meseret seems sick
and has loud breathing
 What should they do?
88
Case Study: Meseret (9)
 Mom is due to return in a short time. She
usually comes home late morning to feed the
baby
 When she arrives you escort her to the clinic
with the baby
 Meseret is brought in to the nurse who weighs
her. Breathing seems fine now, but the child
weighs the same as last visit
89
Meseret’s Growth Chart
95%
90%
75%
50%
25%
10%
5%
Birth Weight- 2.5
kg
Weight at 1 mo.3.4 kg
Weight at 2
mos.- 3.4 kg
90
Case Study: Meseret (10)—Pertinent
Physical Exam
 On examination, the thrush is still visible and
lymph nodes are somewhat larger
 Infant diagnostic tests are not yet back. You ask
the nurse to call the lab and they have no record
of the sample
 What would you do now?
91
Case Study: Meseret (11)
 You decide that the child does not require hospitalization
but ask mom to return in two days
 You order:
 CXR
 CD4 count
 Repeat virologic testing
 Test Results:
 The CD4 is 1200, 13%
 DNA PCR results are not ready
 CXR is normal
 Does this child have HIV infection?
92
Case Study: Meseret (12)
 The team decides that the child most likely has
HIV infection and requires treatment
 Thrush
 Failure to thrive ( WHO Stage III)
 Low CD4 (<25% for infant <11months of age)
 What will you tell the mother?
 What will you do to confirm the child’s infection
status?
93
Case Study: Meseret (13)
 Meseret was continued on CTX, nystatin for
thrush and started on ARVs
 Both initial and repeat DNA PCR results were
positive when test results were finally available
94
Case Study: Tsegenet
 Mom brings her 10 week old baby, Tsegenet, for
a return visit
 The baby has been receiving cotrimoxazole
since 4 weeks of age
 She is breast feeding well and has not been sick
 An HIV test was sent at the previous visit and
mom is anxious to know the results
 The team discussed this family last week during
the multidisciplinary meeting
95
Case Study: Tsegenet (2)
 DNA-PCR results were positive
 The team talked about how to share the news
with the parents
 What will you say to her mother when she
comes to the clinic?
96
Case Study: Tsegenet (3)
 Tsegenet appears well with a normal physical
examination
 Growth is plotted on the 25% percentile for weight,
height and head circumference
 She smiles, makes good eye contact, and reaches
out
 She is breast feeding and receiving additional foods and
water from an aunt
 Mom works several days each week
97
Case Study: Tsegenet (4)—Growth Curve
98
Case Study: Tsegenet (5)—Clinical
Questions
 Given the laboratory result and the clinical
findings, do you think this child is HIV-infected?
 How will you manage the child?
 What will you tell the mother?
99
Case Study: Tsegenet (6)
 Mom returns with the baby in a month
 The repeat DNA PCR test is negative and the
baby is still thriving
 What will you do?
100
Case Study: Tsegenet (7)—Clinical Question
 Which of the following actions would you
consider?





Repeat DNA-PCR testing
CD4
Continue cotrimoxazole
Monitor closely
Rapid antibody screen at 12 months
101
Case Study: Tsegenet (8)—Case Conclusion
 The team was unsure about the lab tests, but
decided to:
 Continue the CTX for now
 Schedule more frequent follow-up, at the same time
as mom’s visits
 Work with the mom and aunt to wean early
 At 12 months Tsegenet tested HIV Ab negative
102
Key Points
 Infant diagnosis can be a complex and lengthy process
 Early virologic testing should be used to identify the
infected infant at highest risk for disease progression
 Specialized virologic tests are used to diagnose HIV
infection in a child <18 months
 Two positive virologic tests confirm HIV infection in an exposed
infant
 The presence of HIV antibody in a child >18 months
defines HIV infection
103
Key Points
 Clinical reasoning is critical to diagnosing infants with HIV
 Virologic tests may be unreliable or unavailable, making clinical
evaluation important
 HIV can be diagnosed without a definitive virologic test in an ill child
with clinical and immunological evidence of infection
 The diagnosis should be confirmed with virologic testing, response
to treatment and/or antibody testing >18 months
 The multidisciplinary team has numerous critical roles in this
process
 The parent or caretaker is the key player, and must be educated and
supported on this logistically, emotionally, socially and medically
complicated path
104
Pediatric Disclosure:
Talking to Children about HIV
Learning Objectives
 List important differences between adult
disclosure and pediatric disclosure of HIV status
 Discuss advantages/disadvantages of
disclosing/not disclosing HIV status to a child
 Discuss strategies to use during pediatric
disclosure of HIV status
106
Disclosing to Children
 Must consider:
 Needs, feelings, beliefs of the child and needs,
feelings, beliefs of the parent(s)/caretaker(s)
• Pediatric health care providers traditionally advocate for
the needs of the child
• Multidisciplinary teams advocate for the needs of the
family
 Current and evolving developmental and cognitive
stage of the child
 Existing status of family dynamics and communication
107
Reasons Parents are Reluctant to Disclose
 Fear of impact of disclosure on child’s
psychological status and emotional health
 Reduce child’s will to live
 Depression in child
 Fear of inadvertent disclosure to others by child
 Child won’t keep secrets
 Protecting child from social rejection and stigma
 Guilt about transmission
 Association with sexual taboos
AAP, Pediatrics 1999;103:164
Lipson M, Hasting Ctr Rpt 1993;23:6
108
Reasons Parents are
Reluctant to Disclose (2)
 Difficulty coping with their own illness or illness
of other loved ones
 Established coping strategies within families
 Traditional silence around illness and disease
 Limited communication within families
 Denial as coping strategy
 Belief that child will not understand
 Children as hope for future
 Avoid thinking of HIV keeps death away
AAP, Pediatrics 1999;103:164
Lipson M, Hasting Ctr Rpt 1993;23:6
109
Do You Believe Children Should Be
Informed of Their HIV Status?
 If yes, why?
 If no, why not?
110
Reasons to Disclose
 Undisclosed children may
 Develop fantasies about their illness
 Feel isolated from sources of support
 Learn HIV status inadvertently
 Children often want and ask to know what is wrong; may
already know diagnosis but are keeping the secret or
waiting for the parent to tell
 With other chronic and fatal illnesses children who know
their status have
 Higher self-esteem
 Lower rates of depression
 Lower rates of parental depression
 Recognition of child’s autonomy
 Children achieve mastery over their lives as they age
AAP, Pediatrics 1999;103:164
Lipson M, Hasting Ctr Rpt 1993;23:6
111
How to Disclose
 Disclosure is more than revealing HIV status
 Disclosure is an ongoing process
 Parents/caregivers should be encouraged to
begin and continue a dialogue about health
issues with their child beginning at an early age
 Simple explanation of nature of illness for youngest
children
 Disclosure about nature and consequences for older
children
 When to use the words “HIV/AIDS” will vary with
the needs of the child and family
112
How to Disclose (2)
 Let the child be the guide
 Individualize the approach. Tailor discussion according to
child's:
 Age
 Cognitive development
• Use tools and language for different developmental
capacities: drawing, storytelling, play, drama
 Level of maturity
• Assess coping skills of the child
 Health status
• Terminally ill child may benefit from discussion about death
rather than specific diagnosis
113
Assisting Families to Get Ready for
Disclosure




Preparation
Education
Planning
Follow-Up
114
Assisting Families to Get Ready for
Disclosure (2)
 Preparation
 Why disclose now?
 What do you want to communicate to your child?
 What will be the most difficult questions for you to answer when
your child knows his/her HIV status?
 Acknowledge difficulty of disclosure and affirm motivation to
begin process
 Education
 Tell parents how to explain HIV transmission to child
 Anticipate questions and responses from child
 Discuss expectations for what will happen after disclosure
115
Assisting Families to Get Ready for
Disclosure (3)
 Planning




When and where?
Who will be there?
What will you say?
Plans after disclosure?
 Follow-up




Functioning within the school and family
Monitor medical treatment adherence
Disclosure to peers and others
Support groups, counseling
116
Why Counsel Children?
 Helps children cope with emotions and
challenges they experience when they discover
they have HIV/AIDS
 Helps children with HIV to make choices and
decisions that will prolong their life and improve
their quality of life
117
Why Counsel Children? (2)







Establish a helping relationship
Help children tell their story
Listen attentively
Give correct and appropriate information
Help them make informed decisions
Help them recognize and build on their strengths
Help them develop a positive attitude towards
life
118
Counseling Children
 Model open discussion during visits
 Address questions to the child
 Ask child if he/she has questions
 Discuss importance of dialogue and disclosure
early and often
 Routine part of pediatric HIV care
 Use good counseling skills
119
Disclosure and Multidisciplinary Teams
 Members of multidisciplinary teams may find themselves
in conflict around disclosure to children
 Some team members may advocate for pediatric disclosure
 Others, particularly those working with adult caregivers, may
resist disclosure
 Multidisciplinary teams may hold/mirror conflicts
occurring in families
 Needs of the child vs. needs of the adult
 Different opinions of different adults
 Important to retain family-focus and consider decisions in
best interest of the child and the family
120
Case Study: Desta
 Desta is an 11 year old girl. Her mother died five years
ago and she has since lived with her aunt Amsale, uncle
Yared and maternal grandmother Bogalech
 Amsale was enrolled in the ART clinic during her
pregnancy last year. Desta and Yared both tested HIV
positive and were enrolled as well
 Desta was eligible for ARV treatment based on a history
of recurrent varicella zoster, chronic thrush and low
CD4%
 She began ZDV + 3TC + NVP but developed a Grade III
rash. NVP was changed to Kaletra (LPV/r)
 She has done well on treatment
121
Case Study: Desta (2)
Resisting Medications
 Grandmother Bogalech brings Desta for her
monthly visit. She reports that everything is fine
 When asked about missed doses Bogalech
reports that Desta gets all of her medication.
She reluctantly mentions that Desta is fighting
with her about taking her medications
 What Do You Want to Ask Bogalech?
122
Assessing Incomplete Adherence
 Review current regimen
 Inquire about problems administering
medications – obtain a descriptive assessment
 Review WHO, WHAT, WHEN, HOW
123
Case Study: Desta (3)
Refuses Medications
 Bogalech states that Desta no longer wants to
take her medications. She was a “good” girl in
the past and took them without complaint though
the orange pills always made her choke. Now
she doesn’t want them any more
 Desta keeps asking why she has to take these
pills. She wants to know when she will finish
taking them
124
Case Study: Desta (4)
 When you ask Bogalech what Desta knows
about her health she becomes quiet. You notice
a few tears. She doesn’t want to discuss Desta’s
problem. She says that the child is taking
medications now and will be fine
 What should you do?
125
Case Study: Desta (5)
Refuses Medications
 Desta and Bogalech return home. You discuss the case
at next team meeting and decide to approach aunt
Amsale when she comes for her monthly visit
 When asked about Desta’s medication adherence
Amsale notes that she has been resisting taking her
medications
 Amsale feels that Desta should know about her illness.
She and grandmother Bogalech have fought about it
several times. They both take care of Desta, but Amsale
also has her babies to raise. She doesn’t want to fight
with her own mother
 Why do you think Grandmother Bogalech doesn’t want
to discuss HIV with Desta?
 What can the team do to help Desta and her family?
126
Case Study: Desta (6)
Disclosure Process - Beginning a Dialogue
 Meet with family members alone, then together
 Begin a discussion/dialogue about Desta’s health and
behaviors
 Address Bogalech’s concerns about Desta
 Work with family members to enhance communication
 Offer counseling for Desta, other family
members
 Follow general counseling guidelines
 Continue to monitor adherence closely
127
Case Study: Desta (7)
Beginning a Dialogue
 After several family meetings, Amsale takes the
lead and starts to talk with Desta about her
health. Bogalech doesn’t take part in the
conversations, but doesn’t prevent them
 Amsale, who is also taking ART, begins to take
her medicines with Desta. She talks about
staying healthy and having strong blood. After
several weeks Desta begins to ask questions
and stops fighting about her medications.
Amsale and Desta become pill buddies and
complain to each other about the nasty blue pills
128
Case Study: Desta (8)
Desta Continues to Ask More Questions
 Several months later Amsale brings Desta to her
medical appointment. She tells the clinician that
she thinks it is time to tell Desta more about her
illness. Bogalech doesn’t want to take part but
has agreed to let Amsale talk with Desta
 Amsale asks for help
 What would you do to assist Amsale and her
family?
129
Case Study: Desta (9)
Disclosure of HIV Status to Desta
 The team works with Amsale and Yared in
preparation for meeting with Desta. Amsale
asks that the nurse and physician help during
the session
 How do you feel about talking with Desta?
 What will you say?
130
Case Study: Desta (10)
Follow-up Care
 Amsale, Yared, the pediatrician, and the nurse
meet with Desta to disclose her HIV status. The
meeting is very emotional for all participants.
Desta and Amsale choose to meet with the
counselor on a weekly basis to continue talking
about their concerns
131
Case Study: Henok
 Henok is 6 years old and he has a 3-year-old sister, Melke. The
children’s parents have died, and both children now live with their
maternal aunt Rahel and her family. Rahel is pregnant and she is
being followed at the clinic
 During a recent visit Rahel reports that both Melke and Henok have
been sick a lot. She requests that both Melke and Henok be tested
for HIV/AIDS. She also reports that the children do not eat or sleep
well
 What additional information do you want?
 How will you go about arranging for testing of the children?
 How will you explain the testing to the children?
132
Case Study: Henok(2)
 During his blood draw for HIV testing, Henok asks the
nurse what happened to his mother and if something bad
is going to happen to his sister and he. He seems very
worried and frightened
 How will you respond to his questions?
 How will you help his aunt in her parenting of Henok and
Melke?
 What should happen, if anything, while the family is
awaiting test results?
133
Key Points
 Disclosure of HIV status to a child is guided by
the needs of the child and their caregivers
 Disclosure should be part of an ongoing
dialogue about health and treatment
 Disclosure should be guided by the age,
developmental and emotional stages, and health
status of the child
 Disclosure is difficult!
134
Key Points
 Disclosure for children
 Involve the child as well as one or more adults
 Consider:
• Child’s age, developmental stage, feelings, health
status
• Caregiver’s beliefs and feelings
• Family dynamics
 Disclosure for children should not be viewed as
a one-time event but as an ongoing processes
requiring a systematic approach and the varied
skills of a multidisciplinary team
135
Care of HIV-Infected Infants
and Children
Learning Objectives
 Describe goals of care for HIV-infected infants and
children
 Describe common clinical manifestations of HIV disease
in children
 Describe appropriate use of the major components of
routine care for HIV-infected infants & children





Categorize disease stage
Prescribe Cotrimoxazole Preventative Therapy
Perform tuberculosis screening
Evaluate ARV eligibility
Schedule pediatric visits
137
Goals for Care of HIV-Infected Infants &
Children
 Model of care
 Family-centered
 HIV primary care
 Multidisciplinary team
 Maximize health & prevent disease progression





Prevent early death
Prevent OI
Maximize growth and development
Reduce hospitalization rate
Reduce frequency of intercurrent illnesses
138
HIV in Children
 HIV during infancy = primary infection
 Acquisition of HIV can occur in utero, intrapartum, postnatally
(through breast feeding)
 Very high viral load: peak at 6-12 weeks of life
 Multiple factors influence rate of disease progression:





Maternal advanced disease
Maternal vital status
Timing of transmission (peripartum vs. late)
Genetic susceptibility
Virus characteristics
 Likelihood of disease progression is associated with
child’s CD4 count and HIV-1 RNA copy number
139
Clinical Manifestations of
HIV/AIDS
Clinical Infections
 Recurrent bacterial infections
 Account for about 20% of AIDS defining illnesses in infants and
children
 Most are caused by encapsulated organisms such as S.
pnuemoniae and Salmonella, others are Staphylococcus,
enterococcus etc
 Most common serious infections are – pneumonia, bacteremia,
sepsis and meningitis (account for more than 50% of infections
in HIV infected children)
 Management
 Same as in non HIV- infected children
 Occasionally may require longer duration of treatment
141
Common Opportunistic Infections
 Opportunistic infections (OI):
 Generally occur with severe immune
suppression
 Young children have primary infection rather
than reactivation
 Lack of immunity leads to more severe course
than in adults
142
Common OIs: Pneumocystis Pneumonia
(PCP)
 Parasitic infection
 Pneumocystis jiroveci
(formerly Pneumocystis
carinii)
 Diffuse and severe pneumonia
 Characterized by gradual
onset of hypoxia, fever, cough
and respiratory distress
 Peak incidence is between the
age of 3 – 6 months
 Hypoxia with normal CXR/or
there may be diffuse alveolar
disease with granular pattern
Management
 Intravenous/oral trimethoprim
(15 – 20 mg) sulfamethoxazole
(75 – 100 mg)/24hrs every 6
hrs for a total of 21 days
 Adjunctive corticosteroids 2
mg/kg/24 hrs for 7 – 10 days
then gradual tapering over 7 –
14 days
 Alternative if intolerant to
TMP/SMX: Pentamidine
 Prophylaxis
 Lifelong after infection
 HIV-infected children
dependent on clinical stage
and/or immunologic
suppression
143
Common OIs: Mycobacterium Avium
Complex (MAC)
 May cause disseminated
disease in children
 Symptoms are non
specific: weight loss or
failure to thrive, fever,
abdominal pain, diarrhea,
and lymphadenopathy
 Diagnosis can be made
only by Isolation of MAC
from blood, bone marrow
or tissue
 Treatment in children
 Clarithromycin- 7.5 mg
/kg/dose twice daily plus
Ethambutol- 15mg /kg /day
 Prophylaxis (CD4% < 15)
 Clarithromycin 7.5 mg/kg
twice daily
144
Common OIs: Candida Infections
 Oral candidiasis and diaper
dermatitis are the most
common in HIV infected
children
 Three forms
 Atrophic candidiasis
 Chronic hyperplastic
candidiasis
 Angular Cheilitis
 Dysphagia and poor oral
intake, irritability indicates
involvement of the esophagus
 Others: invasive disease,
candidal dermatitis,
onychomycosis
 Management
 Oropharyngeal:
Fluconazole 3-6mg/kg daily
for 7-14 days
 Esophageal disease:
Fluconazole 6mg/kg on day
one then 3-6mg/kg daily for
minimum of 14-21 days
145
Common Viral Infections:
Herpes simplex virus
 The most common cause
of stomatitis in children 1
- 3 years of age
 Pain in the mouth,
salivation, fetor oris, refusal
to eat, high fever, vesicular
lesion that rupture leaving
shallow ulcers
 Typically symptoms
subside with in a week
but in HIV infected
children it is prolonged,
and extensive
Dissemination to involve
the skin and other organs
 Treatment:
 Acyclovir
146
Common Viral Infections
 Chickenpox
 May be prolonged and
complicated by bacterial
infection or visceral
dissemination or
pneumonitis
 Herpes Zoster
 Recurrent, atypical and
chronic, and may need use
of acyclovir
 Measles
 May occur despite
immunization and may
present without the typical
rash
 CMV
 Retinitis, pneumonitis,
esophagitis, gastritis with
pyloric obstruction,
hepatitis, encephalitis are
reported
147
Common CNS Manifestations
 Occurs in 50 – 90% of perinatally infected children in
developing countries
 Most common form is progressive encephalopathy




Loss or plateau of developmental milestones
Cognitive deterioration
Impaired brain growth resulting in acquired microcephaly
Apathy, spasticity, hyperreflexia and gait disturbances and loss
of language and other motor skills
 CT shows cerebra atrophy in 85% of children
 Focal neurologic signs and seizure may occur with
 CNS lymphoma, toxoplasmosis, tuberculoma, stroke
148
Common Cardiovascular
Manifestations
 Dilated cardiomyopathy and left ventricular
hypertrophy are common
 With advanced disease high frequency of
autonomic instability leads to rhythm abnormality
 Gallop rhythm, tachypnea, Hepatosplenomegaly
indicates CHF
 Anticongestive therapy is effective
149
Common GI Manifestations
 Most frequent GI symptoms: persistent or recurrent diarrhea with
malabsorption, abdominal pain, dysphagia and failure to thrive
 A variety of pathogens cause GI symptoms:




Bacteria (salmonella, campylobacter, MAC)
Protozoa (Giardia, cryptosporidium, Isosporia, microsporida)
Viruses (CMV, HSV, Rotavirus)
Fungi (Candida)
 MAC and protozoal infections are severe and protracted
 Other GI manifestations are
 Chronic liver inflammation with or without jaundice
 Pancreatitis with or without abdominal pain
 Chronic cholecystitis
150
Common Skin Manifestations: Bacterial skin
infections
 Folliculitis, cellulitis, skin
abscesses impetigo,
furunculosis and
paronychia may occur
with increasing frequency
 Staphylococcus aureus is
the cause in most
bacterial skin infections
 Good hand washing is
needed to prevent spread
of lesion
 Treatment: Antibiotics
Impetigo
Source: Common Skin Diseases In Africa, Colette van Hees & Ben Haafs
151
Common Skin Manifestations: Seborrheic
Dermatitis/eczema
 Extensive and an early
non specific sign of HIV
infection in infants
 Thick yellow scales on
the scalp but thin scales
over the rest of the body
 High recurrence
 Treatment
Seborrheic dermatitis of the axilla
 Topical steroids
Source: Common Skin Diseases In
Africa, Colette van Hees & Ben Haafs
152
Common Skin Manifestations: Pruritic
Papular eruptions (PPE)




Chronic papular lesion
Etiology unknown
Evenly distributed over the trunk and extremities
A marker of worsening immunosuppression and
may be stigmatizing
 Risk of secondary bacterial infection
 Treatment:
 Antihistamines and steroids
Source: Common Skin Diseases In Africa, Colette van Hees & Ben153
Haafs
Common Skin Manifestations: Scabies
 Pruritic papular eruptions
 In infants and children tend to involve the sole
and the palms
 Norwegian Scabies: generalized scaling and
enlarged crusted plaques
 Treatment:
 Benzylbenzoate lotion 25%
154
Common Hematologic Manifestations
 Unexplained Anemia: 20–
70% of HIV-infected
children
 (Hb < 8g/dL)
 Causes: chronic infection,
poor nutrition, autoimmune
factors, virus associated
conditions (Parvovirus B19)
and drugs
 Leukopenia: in up to 1/3
of infected children (ANC
< 1000/mm3)
 Thrombocytopenia: in
10– 20% of patients
 (< 50,00/mm3)
155
Common Malignant Diseases
 Generally less frequent
compared to adults and
represent less than 2% of
AIDS defining illnesses in
children
 Most frequent:
 Non Hodgkins lymphoma
 Primary CNS lymphoma
 Leiomyosarcoma
 Epstein-Barr virus is
associated with most
cases of lymphomas and
all cases of
leiomyosarcoma
 Kaposi sarcoma due to
human herpes virus 8
occurs less frequently
than in the adults
156
Routine Care for the HIVInfected Child
Components of Routine Care for
the HIV-Infected Child
1.
2.
3.
4.
5.
6.
7.
8.
9.
History (past, interim, parental concerns)
Nutrition evaluation
Developmental assessment
Physical examination
Laboratory evaluation
Staging/classification
Opportunistic infections
ARV eligibility
Assessment & plan
158
1. History
 Why is history important?
 Develop clinical profile for older children entering the
program
 Identify changes in health status since last visit
 Identify changes in home setting that may affect
child’s health
 PAST HISTORY
 Newly enrolled older children
• HIV-related illnesses
• Hospitalizations
• Medications (ARV, OI prophylaxis)
159
1. History (2)
 Interim History
 New health problems
 Signs & symptoms checklist
 HIV-related illness
 Current Medications
 antiTB medications
 Medications for OI prophylaxis e.g. Cotrimoxazole
 Other alternative medications (herbal preparations)
160
2. Nutritional Evaluation
 At every visit:
 Nutrition and feeding history – exclusive
breastfeeding or mixed feeding?
 Weigh, measure and examine child
 Use growth curves to monitor growth pattern
 Any child who is not thriving needs extensive
nutritional history
161
Failure-to-Thrive
 The failure to sustain a normal velocity of weight
and/or height growth during the first 3 years of
life – downward crossing of 2 percentiles over
time
 Can be quantified using growth curves
 May be indication:
 Of HIV disease in exposed infant
 For ARV treatment in infected infant/child
 Of ARV treatment failure in child on therapy
162
3. Developmental Assessment
 At every visit
 Ask about the infant’s development
 Simple questions should focus on four critical
developmental domains; cognitive, motor, language,
and social
 This can be done through observation during the
physical exam or asking the parent
 The developmental checklist may be helpful
 Delayed acquisition of developmental
milestones or loss of previously acquired skills
can be the first sign of HIV encephalopathy
163
3.Developmental Assessment (cont’d)
 Developmental Checklist
 1 month: raises head, crawling
movement, alerts to sound
 2 months: head midline, lifts
chest off table, smiles socially
 4 months: rolls front to back,
laughs
 6 months: sits unsupported,
babbles
 9 months: pulls to stand, says
“mama”
 12 months: walks alone, two
words
164
4. Physical Examination
 At every visit
 Perform careful physical examination
 Initial exam should be comprehensive including
examination of all organ systems
 Identify any HIV related physical findings; thrush,
lymphadenopathy, organomegaly,
dermatitis,encepatholpathy etc
 Subsequent exams can be guided by findings on
the symptom/sign checklist
165
5. Laboratory Evaluation
 Which Laboratory Tests Need To Be Done?





Complete Blood Count
CXR if clinically indicated
CD4 Count
Pregnancy test for sexually active adolescent females
CD4 number and percent
• When infant is determined to be HIV-infected
• Upon enrollment for older children
• Every six months there after
166
The Use of CD4 Count in Children
 CD4 counts and percentages in healthy infants at birth
are very high at birth and during the first year of life and
then decline
 The absolute CD4 count during the first year of life is
more than 3 times that of adults
 Because of these differences, adult values do not apply
until age 6
 CD4 count of 500 is considered okay for a 7 year old but is
severe suppression for a 6 month old
 CD4% is a more stable value than absolute number, so
percentage is preferred in children under 5 years of age
167
Calculating the CD4 Percentage
 Calculate the CD4 percentage for a 13 month
old HIV-infected infant






CD4 absolute is 640mm3
WBC is 10,000mm3
N-38%, L 48%, M-12%, E-2%
Calculate the TLC = 10,000 x .48 = 4800
The CD4 percentage= 640 X 100 = 13%
4800
168
WHO Immunologic Categories
Age related CD4 values
Classification of HIVassociated
immunodeficiency
<11mo
(%)
12-35mo
(%)
36-59mo
(%)
5 years
(mm3)
Not significant
>35
>30
>25
>500
Mild
30-35
25-30
20-25
350-499
Advanced
25-30
20-25
15-20
200-349
Severe
<25
<20
<15
<200 or <15%
169
6. Staging and Classification
 Clinical staging should be performed at every
visit
 Why is clinical staging important?
 To assess disease severity
 To monitor disease progression
 Criteria for ARV therapy
170
Clinical Staging of Pediatric HIV/AIDS
 Old WHO clinical stages:
 Three stages
 Didn’t capture many disease manifestations
 Didn’t include measures of immunologic status
 New WHO clinical staging:
 Four clinical disease categories; asymptomatic, mild,
advance and severe
 Expanded comprehensive list of associated
conditions based on prognosis
 Standardized criteria for presumptive and definitive
171
diagnosis
WHO Classification of HIV Associated
Clinical Disease
Clinical Classification
WHO Clinical stage
Asymptomatic
1
Mild
2
Advanced
3
Severe
4
172
WHO Staging for <15 Years Old
Clinical Stage 1 (Asymptomatic)
Asymptomatic
PGL
Clinical Stage 2 (Mild)
Hepatosplenomeagly
Papular pruritic eruptions,
Extensive wart virus infection
Extensive molluscum contagiousum
Fungal nail infections,
Recurrent oral ulcerations
Linear gingival erythema (LGE)
Angular cheilitis
Parotid enlargement
Herpes zoster
Recurrent or Chronic URTI (otitis media, otorrhea, sinusitis)
173
WHO staging for <15 Years Old (2)
Clinical Stage 3 (Advanced)
Conditions where a presumptive diagnosis can be made on the basis of clinical signs or
simple investigations:
Moderate unexplained malnutrition not adequately responding to standard therapy
Unexplained persistent diarrhea (14 days or more)
Unexplained persistent fever (intermittent or constant for longer than one month)
Oral Candidiasis (outside neonatal period),
Oral hairy leucoplakia
Acute necrotizing ulcerative gingivitis/periodontitis
Pulmonary TB
Severe recurrent bacterial pneumonia
Conditions where confirmatory diagnostic testing is necessary:
Unexplained anemia (<8mg/dl),and/or neutropenia (<500/mm3) and/or thrombocytopenia,
(<50,000/mm3) for >1 month
Chronic HIV associated lung disease including bronchiectasis
Symptomatic lymphoid interstitial pneumonitis (LIP)
174
WHO staging for <15 Years Old (3)
Clinical Stage 4 (Severe)
Conditions where a presumptive diagnosis can be made on the basis of clinical signs or
simple investigations:
Unexplained severe wasting or severe malnutrition not adequately responding to standard therapy
Pneumocystis pneumonia
Recurrent severe bacterial infections (empyema, pyomyositis, bone or joint infection, meningitis, but
excluding pneumonia)
Chronic herpes simplex infection (orolabial or cutanoeus > 1 month, visceral of any duration)
Kaposi’s sarcoma, esophageal candidiasis, CNS toxoplasmosis, HIV encephalopathy
Conditions where confirmatory diagnostic test is necessary:
CMV infection (retinitis or infection of organs other than liver, spleen or lymph nodes; onset at the age
of 1 month or more)
Extrapulmonary cryptococcosis including meningitis
Any disseminated mycosis (e.g. extrapulmonary histoplasmmosis, coccidiomycosis, penicillosis)
Cryptosporidiosis, isosporiasis
Disseminated non-tuberculous mycobacteria infection
Candida of the trachea, bronchi or lungs
Acquired HIV associated rectal fistula, cerebral or B-cell lymphoma
Progressive multifocal leucoencephalopathy (PML)
HIV associated cardiomyopathy or HIV associated nephropathy
175
WHO Classification of HIV-associated
Immunodeficiency in Infants and Children
Immunological
Classification
<12 months
(CD4 %)
Not significant
> 35%
> 30%
> 25%
> 500
Mild
30-35%
25-30%
20-25%
350-499
Advanced
25-30%
20-25%
15-20%
200-349
Severe
< 25%
< 20%
< 15%
< 200 or
15%
12-35
36-59
months (CD4 months (CD4
%)
%)
> 5 years
(CD4
cells/mm3)
176
Case 1: Henok
 Henok is 12 months old with HIV infection. He
has had no major illnesses or hospitalizations
 He has bilateral cervical, inguinal and axillary
adenopathy, persistent oral and genital
candidiasis, and is being treated for his 4th
episode of otitis media. His growth is at the 10th
percentile
 What WHO stage is Henok?
177
7. Opportunistic Infections
 Occurs with severe immune suppression
 Young children have primary infection rather
than reactivation as in adults
 Immature immune system of the infant leads to
more fulminant course than in adults
 Prophylaxis prevents disease progression and
morbidity and mortality!
178
PCP Pneumonia
 Parasitic infection
 Pneumocystis jiroveci (formerly Pneumocystis carinii)
 One of the most commonly occurring
opportunistic infections in infants and young
children with a very high mortality rate
 Without prophylaxis, 40% of infants and children
with AIDS experience PCP
 Prophylactic cotrimoxazole is one of the most
important interventions for HIV-exposed infants and
HIV-infected infants and children
179
PCP Pneumonia
 Clinical presentation characterized by sudden
onset of hypoxia, fever, cough and respiratory
distress
 In some, sub-acute presentation
 Peak incidence occurs between the age of 3–6
months with highest mortality in children <1 year
of age
 Patients may have hypoxia with normal CXR or
there may be diffuse alveolar disease with
granular pattern
180
Prophylaxis Regimens
 Cotrimoxazole suspension
 Recommended dosing is based on 4mg/kg of the
trimethoprim portion once each day
 Use weight band chart for dosing
 Toxicities* include
 Rash
 Fever
 Bone marrow suppression (neutropenia)
*infrequent in infants
181
Tuberculosis: Background
 Most common opportunistic infection among
HIV-infected patients in Africa, SE Asia
 Leading cause of AIDS-related deaths
worldwide: 1/3 of all AIDS-related deaths are
due to TB
 Can be prevented by:
 Treatment of latent TB infection (preventive therapy)
 Use of antiretroviral therapy
182
Special Issues for Children
 High rates of co-infection (HIV and TB)
 Zambia: 69% hospitalized with clinical TB test HIV+
 Cote d’Ivoire: 23.4%
 Johannesburg: 42%
 Higher risk of progression from latent to TB
disease compared with adults
 Associated with severe complications
 Meningitis
 Miliary TB
183
Special Issues for Children (2)
 Difficult to diagnose
 Limited yield of diagnostic procedures:
• Poor sputum production
• Low yield of gastric aspiration
• Sputum induction and bronchoscopy not routinely used
 Multiple varied clinical manifestations
 Overlap with other HIV disease manifestations
 BCG vaccination results in false positive Tuberculin
Skin Testing (TST)
 Limited sensitivity of TST in HIV-infected children
184
TST Survey in Children, Botswana
80
70
60
50
40
% TST positive
30
20
10
0
0 mm
1-9mm
10-14mm
>15mm
TST Reaction Size (mm)
MMWR 1997, 46(36);846
185
Impact of BCG Vaccination
 WHO estimates 79% of population vaccinated
 Given at birth or during newborn period
 Thought to prevent severe TB complications in
young children, i.e. disseminated disease and
meningitis
 Can result in reactive TST
 No reliable method to distinguish “true-positive” TST
caused by M. tuberculosis infection from “falsepositive” TST caused by BCG vaccination
186
Tuberculosis Screening
 Targeted history at each evaluation
 Symptom checklist
 Inquire about household contacts with TB
• Establish risk to infant/child
• Make sure those with TB in the household are appropriately
treated
 Tuberculin skin testing (TST) of
 Children with positive symptom screen or clinical findings
consistent with TB
 Household contacts of adult with TB disease
 Annually for all children with HIV infection beginning at 1 year of
age
187
TST Placement and Reading
 Intradermal placement of .1 ml 5TU PPD
 Read 2-3 days after placing test by trained
worker or health care provider
 Feel for induration
 Color change without induration is not included in
measurement
 Use a ruler or calipers
 Document exact size (mm) of reaction
 ≥ 5 mm induration considered positive in an HIVinfected child
188
Positive TST (>5mm)
 Exclude active TB as per local and national guidelines
 Symptom checklist and physical exam
 Chest X-ray when available
 For TB disease
 Follow local and national guidelines
 For LBTI
 INH (10-15mg/kg, maximum 300 mg) daily for 6 months
 Vitamin B6 generally not given to children unless:
• Severe malnutrition
• Breast feeding
• AIDS
• Pregnant adolescent
189
8. ARV Eligibility
 WHO Recommendations for Initiating ART in Infants and
Children
 Children with WHO Stage 4 and most WHO stage 3
should initiate ART
 CD4 can be used to guide ART initiation for some Stage 3
diagnoses (TB, LIP)
 Children with WHO Stages 1 and 2 should only initiate
ART if they have evidence of advanced immune
suppression
 Children with severe immune suppression independent
of WHO stage
190
9. Assessment & Plan
 Synthesize components of evaluation




Diagnose and manage complications
Order laboratory studies
Refer for counseling/support groups
Follow-up appointment
191
What is the Follow-up Schedule for the
HIV-Infected Child?
Ages 0-6 months
6-24 months
Monthly
Every 3 months
>24 months
 Symptomatic
 Asymptomatic
Every 3 months
 Receiving ARV
Every 6 months
Weekly for 8 weeks,
monthly thereafter
192
Pediatric Antiretroviral
Therapy
Learning Objectives
 Describe WHO clinical and immunological
criteria for ART initiation in infants and children
 Describe preparation of the family for ART
 Identify and manage ARV toxicities
 Recognize treatment failure
194
Children Are Not Small Adults
 Age-related differences between children & adults




Body composition
Renal excretion
Liver metabolism
Gastrointestinal function
 Drug metabolism in children varies with age and
maturation leads to differences in:
 Drug distribution and clearance
 Drug dosing and drug toxicities
• Pharmacokinetic (PK) data not consistently available in
young children
• Variations in PK (between and within individuals) frequently
greater in children
195
Requirements Prior to ART
 Confirm HIV Diagnosis and Eligibility
 Laboratory confirmation as soon as possible
 WHO Clinical and Immunological Staging Criteria
 Identify and fully counsel caregivers
 Confirm availability of support services (family, social,
inpatient care etc.)
 Ensure access to nutrition and prophylaxis
 Availability of consistent caregiver for
administration/supervision – will vary with family
structure
 Ability to keep follow-up appointments
196
WHO Criteria for ART Initiation in Infants
and Children < 13 years
 Children with WHO Stage IV and most WHO
stage III should initiate ART
 CD4 can be used to guide ART initiation for some
stage III diagnoses (TB, LIP)
 Children with WHO Stages I and II should only
initiate ART if they have evidence of advanced
immune suppression
 Children with severe immune suppression
independent of WHO stage
197
New WHO Criteria for Starting ART in
Infants & Children
WHO Pediatric
Stage
Availability of
CD4 cell assay
Age specific recommendation
<18 months
>18 months
CD4
IV
Treat All
No CD4
CD4
III
Treat All
No CD4
Treat all except those with
TB, LIP,OHL,
thrombocytopenia, also
take into account CD4
value
Treat all
CD4
CD4 guided
No CD4
TLC -guided
CD4
CD4 guided
No CD4
Do not treat
II
I
198
WHO Age-Related CD4 Values for Starting
ART in Infants & Children
Age specific recommendations to initiate ARTb
Immunological
markera
CD4%
CD4 count
<12mo
12-35mo
36-59mo
>5 years
25 %
20%
15%
15%
1500cells/mm3
750 cells/mm3
350cells/mm3
200cells/mm3
2500cells/mm3
1500cells/mm3
To be used only in absence of CD4 assay:
Total
Lymphocyte
count
4000cells/mm3
3000cells/mm3
199
WHO Criteria for Starting ART: Infant with
Presumptive Diagnosis-Severe HIV Disease
 HIV antibody positive and
 Diagnosis of Stage IV

OR
 Symptomatic with ≥ 2 of the following:
• Oral thrush
• Severe pneumonia
• Severe sepsis
 Supporting factors
 Recent maternal death
 Advanced HIV disease in the mother
 CD4 <20%
 Laboratory confirmation should be sought as soon as
possible depending on available resources
200
Eligibility of Children >13 years of age
 WHO stage 4 irrespective of CD4 cell count
 WHO stage 3 HIV disease and CD4 < 350
 CD4 < 200 irrespective of WHO stage
 In situations of rapidly deteriorating health status and
lack of virologic test availability, a presumptive diagnosis
can be done
 A presumptive clinical diagnosis of severe HIV
necessitates management of presenting acute illnesses
and management of HIV including the initiation of ART
201
Preparing for ART
 Complex adherence challenges for children
 Requires collaboration of child, parent, and all
secondary caretakers
 Family needs support around long-term therapy,
changing regimens, and doses
 Issues of disclosure and multiple caretakers
complicate complete adherence
 Ongoing support for evolving adherence needs as
child develops with age
 Prepare family for adherence
202
Points of Caution
 Consider any medical contraindications to firstline regimens using




Medical history
Symptom checklist
Physical examination
Laboratory studies (renal function, liver function, and
CBC, pregnancy test in sexually active females, and
CXR if clinically indicated)
203
Medical Contraindications to ART
 Severe Anemia (Hb<6.9 gdl) Contraindication to AZT, replace with
d4T
 Severe Neutropenia (ANC<250 mm3) AZT use requires close
monitoring. Can substitute d4T if ANC falls
 Severe Renal Insufficiency (Creatinine > 3 times normal)
Contraindication to ARV use. Patient not eligible for ART
 Severe Hepatic Insufficiency (LFTs > 5 times normal)
Contraindication to NVP use. Use EFV in children older than 3, PI
treatment suggested for small children
 History of prior ARV use Potential for ARV resistance. Consult for
expert management
 Current use of rifampin containing TB regimen- Interactions with
NVP. If CD4 is high, consider deferring ART or use ritonavir
containing regimen for children under 3 and EFV containing regimen
for children older than 3
204
First Line Regimens
 Preferred pediatric first line regimes:
 Children under the age of 3
 AZT+3TC+NVP or
 d4T+3TC+NVP or
 ABC+3TC+NVP
 Children older than 3 years (>10kg)
 AZT+3TC+NVP/EFV
 d4T+3TC+NVP/EFV
 ABC+3TC+NVP/EFV
or
or
 Additional dual NRTI backbone include ABC+ AZT or
ABC+d4T
205
Special Circumstances
 WHO recommends Triple NRTI
 (AZT+3TC+ABC or d4T + 3TC +ABC)
 as alternative option for initial therapy under
certain circumstances:
 Infants and children < 3years receiving TB treatment
where NVP or PI cannot be used because of
interactions with rifampin
 Pregnant adolescent with CD4 cell > 250/mm3 in
which both NVP and EFV are contraindicated and PI
based regimes are not available
206
Dosing for Pediatric ARVs
 Dosing is weight dependent and must be
adjusted for significant weight gain/loss
 Check weight and height at each visit and adjust
dosage when necessary
 Failure to adjust for weight gain can lead to
underdosage and development of resistance
 Failure to adjust for weight loss can lead to
overdosing and toxicity
 Review dose changes and reasons for changes
with family
207
ICAP Pediatric ARV Dosing Chart
208
Zidovudine (AZT)
 Formulation
 Syrup:10 mg/ml
 Capsules: 100 mg; 250mg
 Tablet: 300mg
 May be crushed and combined with food
 Light sensitive, needs to be stored in a glass jar
 Should not be used with d4T because of
possible antagonism
 Monitor side effects and toxicity
209
Lamivudine (3TC)
 Formulation
 Oral solution: 10 mg/ml
 Tablet: 150 mg
 Generally well tolerated
 Store solution at room temperature
 Tablet can be mixed with water or food and
taken immediately
 Use within one month of opening the bottle
 Monitor side effects and toxicity
210
Stavudine (d4T)
 Formulation
 Oral solution: 1mg/ml
 Capsules: 15mg, 20mg, 30 mg
 Solution must be refrigerated
 Capsules may be opened and mixed with small
amount of food
 Should not be used with AZT because of
possible antagonism
 Monitor side effects and toxicity
211
Abacavir (ABC)
 Formulation
 Oral solution: 20mg/ml
 Tablet: 300mg
 Can be given with food
 Tablet can be crushed and mixed with small
amount of water or food and immediately
ingested
 Monitor side effects and toxicity
212
Nevirapine (NVP)
 Formulation
 Oral solution: 10 mg/ml
 Tablet: 200 mg
 Can be given with food
 Store suspension at room temperature; must be shaken
well
 NVP is initiated at a lower dose and increased in a
stepwise fashion
 Monitor for side effects and toxicity
 Liver toxicity can occur but is less common than in adults, can be
fatal
 Discontinue for grade 3 toxicity: substitution with efavirenz has
been successful in adults, but little data is available for children
213
Efavirenz (EFV)
 Formulation
 Syrup: 30mg/ml (for children > 3 years)
 Capsules: 50mg, 100mg, 200 mg
 Not indicated for children under 3 years of age or less than 10 kg
 Capsules can be mixed with sweet foods or jam to disguise peppery
taste
 Can be given with food but avoid high-fat meals which decrease
absorption by 50%
 Best given at bedtime to reduce CNS side effects
 Monitor for side effects and toxicity
 Should not be prescribed for adolescent females who are at risk for
becoming pregnant because of teratogenicity
 Rash is more frequent in children than adults but it is generally milder
214
Special Considerations in Prescribing First
Line Regimens
 Never prescribe efavirenz to a child under the
age of 3. Proper dosing has not been
determined for any child <3yrs or <10kg
 Stavudine (d4T) liquid requires refrigeration.
Families can be taught to open capsules but this
may be complex. Zidovudine may be preferable
 In children who were previously exposed to NVP
as a PMTCT regimen, NNRTI resistance may
develop. While this resistance generally fades
within the first year, this may impact the efficacy
of the NNRTI-based regimen
215
How to Monitor ARV Therapy




Clinical
Laboratory
Treatment adherence
Program adherence: keeping visit appointments
216
Clinical Monitoring
 Weekly visits for the first 8 weeks
 Assess adherence, side effects/toxicity, immune
reconstitution and growth
 Symptom checklist and targeted physical exam
 Review and recalculate dose, if needed, at each visit
based on weight
 Dispense one week of medication
 To decrease burden on the family, follow-up visits can
be combined with other health care visits
217
Clinical Monitoring (2)
 Monthly visits after the first 8 weeks if adherence
is excellent
 At each visit:









Interim history
Symptom checklist
Targeted physical exam
Growth and nutritional assessment
Developmental assessment
Psychosocial assessment
Adherence with caregiver and older child when appropriate
ARV prescription (recalculate doses)
Referral for support services as needed
218
Laboratory Monitoring
 CD4 count and percent
 Every 6 months to monitor ART efficacy
 Hg at 1 month for those on AZT
 Thereafter, if symptoms indicate
 Abnormal findings on history or physical may
warrant additional laboratory testing
 Abnormal lab results may indicate ART toxicities,
intercurrent illnesses, and/or advancing disease
219
Defining ART Success
 Mild or no reported side effects
 Excellent adherence
 Improved clinical status in 6 months
 Improved growth
 Improvement in neurological symptoms and
development
 No new AIDS defining illness
 Fewer intercurrent illnesses
 Improved or stabilized immune status in 6
months
220
Attending to ART Toxicities
 In general, ART is well tolerated
 Similar to adult ART care, high level of attention
needs to be given to potential adverse effects
such as: ART toxicity, immune reconstitution,
intercurrent illness, disease progression, drug
interaction
 Please refer to detailed toxicity information
covered in the adult sections
221
Attending to ART Toxicities
 Remember:
 Clinical judgment is important:
 Something other than ART may be causing the
adverse effect
 Lab error might confound the assessment of toxicity
severity
 Every individual is unique and might not fit precisely
into a table or guideline
 Response to management plan may be the only way
to determine if symptoms/problems are due to ART
toxicity
222
Switching Single Drug for Toxicity
First- line
drug
Major potential toxicity
Drug substitution
ABC
Hypersensitivity reaction—DO NOT
RECHALLENGE
AZT
Lactic acidosis
ABC
Severe gastro-intestinal intolerance
d4T or ABC
Severe anemia or neutropenia
d4T or ABC
Lactic acidosis
ABC
AZT
d4T
Lipoatrophy / metabolic syndrome
Peripheral neuropathy
AZT or ABC
Pancreatitis
223
Switching Single Drug for Toxicity
First- line drug
Major potential toxicity
Drug substitution
Persistent severe CNS toxicity
NVP
Potential teratogenicity
NVP
Severe hepatotoxicity
EFV
Hypersensitivity
DO NOT RECHALLENGE:
use
Triple NNRTI (disadvantage,
EFV
NVP
Severe life threatening rash
(Stevens Johnson Syndrome)
may be less potent)
PI (disadvantage, premature start of
2nd line ARV drug)
224
Recognizing Treatment Failure
 Inadequate adherence is the most common cause of
treatment failure in children
 Issues to consider with regard to adherence:
 Who administers drug?
 How is drug administered?
 Is it the drug?
 Resistance to specific agents may have a significant
impact on treatment efficacy
 Resistance to specific drugs can develop secondary to
inadequate adherence, inadequate drug levels and selection of
pre-existing mutations with selective pressure of present
regimen
225
Clinical Indications of Treatment Failure
 Lack of or decline in growth rate in children who
show an initial response to treatment (WHO
Stage III or IV)
 Loss of neurodevelopmental milestones or
development of encephalopathy (WHO Stage
IV)
 Occurrence of new opportunistic infections or
malignancies or recurrence of infections, such
as oral candidiasis that is refractory to treatment
or esophageal candidiasis (WHO Stage III or IV)
226
Immunologic Indicators of Treatment Failure
 Development of age-related severe
immunodeficiency after initial immune recovery
 Despite > 24 weeks of treatment
 Confirmed with at least one subsequent CD4
measurement
 Lack of improvement in CD4 cell percentage or
absolute count despite >24 weeks of treatment
 Rapid rate of decline to or below threshold of
age-related severe immunodeficiency
227
Second-Line Regimens
 ART sequencing based on resistance patterns
associated with specific agents
 Goal is to replace failing first-line regimen with a
second that has minimal potential for cross
resistance
 Choices balance potency, toxicity, formulation,
and cost
 As new data becomes available, these may
change
228
Pediatric Second-Line Regimens
 AZT or d4T: substitute abacavir (ABC)
 3TC: substitute didanosine (ddI)
 NVP or EFV: substitute lopinavir/ritonavir
(LPV/ritonavir) or if no cold chain available, then
nelfinavir
229
Abacavir (ABC)
 Formulation
 Oral solution: 20 mg/ml
 Tablets: 300 mg
 Can take with or without food
 Most serious adverse event is acute
hypersensitivity reaction – rare (<3%) but can be
fatal
 Monitor side effects and toxicity
 Do not rechallenge if hypersensitivity reaction is
suspected
230
Didanosine (ddI)
 Formulation
 25, 50, 100, 200 mg tabs
 10 mg/ml liquid
 For proper buffer dose, 2 tabs must be used
 Administer on empty stomach 1 hour before or 2
hours after meal; don’t take with acidic drinks but
can take with water
 This may make administration of regimen difficult, as
drugs may not all be taken together
 Monitor side effects and toxicity
231
Lopinavir/ritonavir (Kaletra)
 Formulation – dose based on lopinavir
 Solution: 80/20 mg/ml
 Capsule: 133.3/33.3 mg
 Must take with food
 Can be stored at room temperature once
dispensed – stable for 60 days
 Bad taste – can be masked with sweets
 A very “forgiving” drug
 Monitor side effects and toxicity
232
Role of the Multidisciplinary Team
 Non-clinicians may be the first to hear about a
medication toxicity. Their finding need to be
communicated to providers who should note
patient symptoms/signs in the medical record
 Decisions and follow-up should be discussed in
multidisciplinary team meetings
 Adherence needs to be discussed at every visit
and contact (clinician, counselors etc)
233
Patient Education
 The parent/patient should be aware of what to
expect when starting ART and while receiving
ART
 The parent/patient should be aware of possible
side effects
 The parent/patient should know what to do if she
believes she is experiencing a side effect
(especially if this happens when the clinic is
closed)
234
Case Study
 A 6 month old baby girl, Mulu, presents to the
clinic 12 days after her appointment date
 Mother complains her daughter has had a
cough and diarrhea for the last 2 weeks
235
Case Continuation
 Mother was enrolled in PMTCT program and
both baby and mother took Nevirapine
 Baby was enrolled at the HIV clinic at 4 weeks
and started on Cotrimazole prophylaxis
 Exclusively breastfed for 6 months
 Weaned with no breastfeeding for last 2 weeks
 Weight gain normal for first 6 months
 Adherence to care has been poor with mother
missing many appointment dates
236
Case Continuation
 Diarrhea has been persistent with loose watery
stools passed 6 times each day for the last 2
weeks
 Little improvement on oral rehydration therapy
 Cough has been progressive
 Unresponsive to Amoxicillin
 Fever, lethargy and poor feeding
 File shows 1st DNA PCR was negative
237
Clinical Exam
 Vitals: Weight 5.4 kg (1 month ago was 6.4 kg),
Temperature 37.8 C
 Some wasting present with mild dehydration
 Child irritable and listless
 Chest exam finds left sided bronchial breathing
 Rest of the exam is unremarkable
238
Growth Chart
239
Case Continuation
 Chest X-ray showed left lower lobe pneumonia
 Prescribe Erythromycin





Oral rehydration therapy for diarrhea
Cotrimoxazole prophylaxis
Nutritional counseling and advice
Multidisciplinary team meeting planned
Follow up in 2 weeks
240
Case Continuation
 Mother does not return till her 7 month visit
 Baby’s cough resolved, however diarrhea has
persisted
 No fever or vomiting noted
 Weight has dropped to 5.2 kg despite mother
following nutritional advice
 She is adherent to cotrimoxazole
 Stool studies from previous visit were normal
241
Case Continuation
 Clinician is concerned this infant might have HIV
and need ART
 He sends DNA PCR, CD4, LFTs, CBC and
chemistry
 Oral rehydration therapy for diarrhea
 He sends mother for adherence training in
anticipation of starting ART at next visit
 Cotrimoxazole prophylaxis
 Nutritional counseling and advice
 Follow up in 2 weeks
242
Case Continuation
 At her next visit her weight is unchanged (5.2Kg)
and diarrhea is still present
 DNA PCR is positive, CD4% done at 7 months
of age is 20%
 Baselines tests were within normal
 Is she eligible for ART?
243
Clinical Question
 Considerations for starting ART
 Is family appropriately prepared?
 Does mother understand critical importance of good
adherence?
 Are there any clinical or laboratory contraindications
to specific drugs?
 What ART would you start?
244
Case Conclusion
 Adherence counseling done and mother understands
importance
 She is put on:
 AZT: 7ml twice a day
 3TC: 2ml twice a day and
 NVP: 2ml once a day
 At next visit 1 week later, she has no new complaints
and is tolerating her medications
 2 weeks later she has gained 500gm
 Since infant is tolerating medications well  escalate the dose of
NVP to 4ml twice a day
245
Summary
 ART can provide life sustaining support for the HIV infected child
 Using clinical staging and CD4 count can help identify the eligible
child
 In the case of rapidly progressing disease, clinical judgment may
identify the eligible child before diagnosis is confirmed
 There are unique adherence challenges for children on ART
 Families need additional support for adherence and frequently
changing dosage requirements
 A child on ART must be monitored carefully in order to identify
adverse events early and respond appropriately
 The multi-disciplinary team plays an important role in assessing
adherence and in monitoring the child on ART
246
Pediatric Adherence
Learning Objectives
 Identify ways to prepare a family for ARV
adherence
 List ways to monitor and support ARV
adherence
 Describe ways to assess adherence
248
Adherence to Treatment: Issues for
Children
 ARV treatment for children requires:
 Collaboration between the child and caregiver(s)
• Commitment of the caregiver(s)
• Cooperation of the child
 ARV treatment for children is complicated by:




Developmental stage/age of the child
Parent-child interaction
Psychosocial milieu
Relatively poor palatability of many pediatric
formulations
 Caregiver factors
249
Reported Difficulties Taking ARV
Medications, PENTA 5
 Taste/Palatability/Volume
 Difficulties with unpleasant flavor and/or smell
 Nausea
 Too many pills
 Social Situations – Fear of disclosure




Visiting or out with friends
Visiting relatives over weekend
Visitors in house
Had to leave child with a friend for the day
Gibb D et al, Pediatr Infect Dis J 2003:22;56
250
Factors Associated with Adherence
 Demographic Variables: age, sex, caregiver
type, caregiver sex, income
 Disclosure to child, to others
 Caregiver-child communication
 Caregiver self-efficacy
 Caregiver health beliefs
 Caregiver depression
 Stress
 Stigma
251
An Approach to Adherence:
Giving Medications to Infants & Children
 Promoting Adherence




Education
Preparation
Monitoring
Support
 Assessing Adherence
 Assessment Methods
 Addressing Barriers
252
Promoting Adherence
1. Education
2. Preparation
Support
Education
Monitoring
Preparation
3. Monitoring
4. Support
253
1. Adherence Education
 Define adherence





Never missing a dose
Keeping to specific times of administration
Taking it the “right” way
Lifelong treatment, even when feeling well
Underscore difficulty of task
 Explain importance of strict adherence
 Use simple terms, visual aids, analogies
 Emphasize need for communication with health care
team
 Trust
 Partnership
 Honesty
254
2. Adherence Preparation
 ARV treatment is rarely an emergency
 Take time to prepare the child and the caregiver
 Personalize medication administration to match the specific aspects
of a child’s and family’s life
 Address the WHO, WHAT, WHEN and HOW of medication
administration.
 WHO will administer the medications?
• Everyday? Weekdays and weekends?
 WHAT medications will be given?
• Familiarity with medication
 WHEN will medications be given?
• Establish specific times and routines
 HOW will medications be given?
• Details of administration: using syringes or measured spoons,
cutting and crushing tablets, with or without food, mixed with
beverage, mixed together, sequencing
255
Questions that Help Assess Readiness
 Has the mother disclosed HIV status to anyone? Do the other
people in the household know about the child’s diagnosis?
 Is there support in the household/family?
 Is the living situation stable?
 Does the mother understand ARV treatments, dosages, expected
outcomes, potential side effects?
 Does the mother appreciate the need for intensive monitoring and
follow-up?
 Does the mother understand the need for strict adherence?
 Has the child tasted the medications?
 How does the child’s developmental level influence ability to take
medications?
 Have the health providers observed medication administration?
256
2. Adherence Preparation (2)
 Other preparatory tools for children:






Taste testing
Observation of dosing
Training for pill swallowing
Behavioral reward system
Role play
Anticipating problems
• Hypothetical scenarios – What would you do
if….vomiting, refusal, fever, other?
257
3. Adherence Monitoring
 No perfect measures
 Emphasize the importance of honest reporting
 Importance of multidisciplinary approach to
monitoring
 Provide all possible support as discussed in
adult ART care
258
4. Adherence Support
 Lifelong adherence to complex medication regimens is
an extremely difficult task!
 Identify and reinforce effective, successful strategies
 Psychosocial support
 Disclosure
 Adherence buddy
 Support groups
 Adherence Aids





Pill boxes
Blister packs
Calendars
Pre-pouring
Labeling syringes
259
What Do You Do When Adherence is
Incomplete?
 Assess why adherence is incomplete
 Address the barriers to adherence
260
Assessing Incomplete Adherence
 Review current regimen
 Inquire about problems administering
medications – obtain a descriptive assessment
 Review WHO, WHAT, WHEN, HOW
 Observe administration
261
Addressing Adherence Barriers: What to Do
Next
 Identify specific barriers to adherence
 Consider stopping current regimen
 Address specific barriers to adherence
 Alter current regimen or change to new regimen
 Formulation or single drug substitution
 New regimen in the case of treatment failure
 Begin again




Adherence education
Adherence preparation
Adherence monitoring
Adherence support
262
Adherence Fatigue
 Do not assume “once adherent, always
adherent”
 It can be anticipated that with time:
 Children may tire of taking medications
 Caretakers may tire of administering/supervising
medication
 Providers may tire of monitoring/supporting
adherence
 Beware of adherence fatigue!
263
Case 1: Kebede
 Kebede is a 2.5 year-old boy who has been
enrolled in the clinic since birth
 He began ZDV + 3TC + NVP at 6 months of age
when he was diagnosed with pneumonia and
failure-to-thrive. He has done very well on this
regimen
264
Kebede’s Current Medications





ZDV
15cc every 12 hours
3TC
6cc every 12 hours
NVP
10cc every 12 hours
Cotrimoxazole 10cc every morning
MVI
1 cc every morning
265
Kebede
 Alem, Kebede’s mother, reports that lately she
has been having trouble giving him medication.
In the past he has always taken the ARV
treatment easily, but over the last several
months it hasn’t gone well
 What questions should you ask Alem?
266
Questions for Alem
 Who gives the medicine? All the time?
 Which medications is he getting?
 What happens when Alem tries to give him his
medication –what does Kebede do?
 Does he 1) refuse; 2)vomit, spit, choke; 3)run away?
 Does this happen all of the time or some of the time?
 Is it one drug in particular or all of the drugs?
 How long does it take to give him his medication?
 Has he missed any of this doses? All of the medications
or just one?
 Has Alem found anything that helps to give his meds?
 Other?
267
Kebede
 Alem reports that he doesn’t like the ZDV. He runs from
her when she tries to give him his medications. She
must capture him, hold him down, force his mouth open
to take the ZDV. He then gags and chokes, often
vomiting the medicine
 He takes the NVP and 3TC, but sometimes she thinks
he doesn’t keep them down either. Alem, having learned
the importance of adherence, is worried
 What do you need to know to begin to determine the
cause of Kebede’s behavior?
268
Possible Reasons for Kebede’s Behavior
Change
 New developmental stage
 Increasing emotional and physical independence,
“terrible twos”
 Changes in household
 Change in schedule
 New changes in caretaker
 New members of household
 Adherence fatigue
 Other
 What do you need to do now?
269
Incomplete Adherence: What to do Next?
 Identify specific barriers to adherence
 Observe medication administration and parent-child interaction
 Address specific barriers to adherence
 Offer explanation for Kebede’s change in behavior
 Alter current regimen or change to new regimen
• Formulation or single drug substitution
• New regimen in the case of treatment failure
 Begin again with adherence
•
•
•
•
Education
Preparation
Monitoring
Support
270
Kebede
 You feel that the problem is probably related
only to the ZDV and may require a change or
alteration in the regimen
 Since Alem understands the importance of
adherence and is committed to Kebede taking
all of his medications, you begin to discuss
options with her
 What are some possible solutions?
271
Other Ways to Give Kebede
Medications
 Consider behavioral interventions
 Reward system
 Explore ways to mask taste
 Mix with liquids
 Mix medications together
 Tasty “chaser”
 Explore other formulations
 Crushed tablet if dosing appropriate
 Other?
272
Kebede: Conclusion
 Dosing:
 You look at the dosing guidelines brochure for each of
Kebede’s medications
 Each ZDV capsule = 100mg
 Together with Alem you decide to change the ZDV to
2 capsules twice daily
 Follow up
 Alem & Kebede return 2 weeks later. Alem reports
success giving Kebede crushed tablets (She crushes
and mixes the tab with sweet pudding) and he takes it
willingly
273
Summary: Adherence to ARV for Children
 There are multiple barriers to adherence
 Successful adherence requires
 Education and preparation before starting treatment
 Assessment and monitoring during treatment
 Most families will have periods of time when
adherence is incomplete
 Barriers to adherence should be assessed and
addressed at each clinic visit
 Providers and families may experience
adherence fatigue
274
Summary
 Adherence for children
 Involve the child as well as one or more adults
 Pay attention to:
• Age, developmental stage, feelings, health status of the
child
• Beliefs and feelings of the caregivers
• Family dynamics
 Adherence for children should be viewed as
ongoing processes requiring:
 Systematic approach
 Varied skills held in multidisciplinary teams
275