Module 9

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Module 9

• Treatment Guidelines for the Management of
  Newborns and Children infected with or exposed to
  HIV in utero

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Objectives

• The epidemiology of HIV among children globally
• How the virus is transmitted to children
• How the diagnosis of HIV is made in babies
• The management of HIV/AIDS in newborns and
  children

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Outline

• How are children infected?
• Management of Children Born to HIV-Positive
  Mothers
• Diagnosing HIV in children
• Starting ART in children gt18 months of age
• Choice of regimens for children

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Children (lt15 years) estimated to be living with
HIV as of end 2003
Eastern Europe Central Asia 8 100
Western Europe 6 200
North America 11 000
East Asia 7 700
North Africa Middle East 21 000
Caribbean 22 000
South South-East Asia 160 000
Latin America 25 000
Sub-Saharan Africa 1.9 million
Oceania 600
Total 2.1 million
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Trends in general mortality among children lt 5
yrs by adult HIV prevalence rate, 1999
110
Zambia
105
HIV prevalence 19.9
100
Relative under-5 mortality (1981 100)
95
Kenya
HIV prevalence 14.1
90
Cameroon
85
HIV prevalence 7.7
80
80
82
84
86
88
90
92
94
96
98
Source Demographic and Health Surveys, Macro
International, USA
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Estimated Impact of AIDSUnder-5 Child Mortality
2010
with AIDS
per 1000 live births
250 200 150 100 50 0
without AIDS
Botswana
Kenya
Malawi
Tanzania
Zambia
Zimbabwe
Source US Bureau of the Census
UNAIDS 1 December 1999
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How are children infected?

• 70-90 of the transmission occurs in the
  peripartum periodduring delivery rather than
  in utero
• Factors that increase transmission include
• Prolonged rupture of membranes
• High maternal viral load
• Low maternal CD4 count (independent of viral
  load)
• Babies of HIV postive mothers who are breast fed
  have a 16 additional risk of transmission.
• Poverty, lack of prenatal and maternity care,
  lack of antiretroviral medicines

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How are children infected?

• Mother to child transmission
• Transmission of HIV from mother to infant occurs
  in about 30 of births of untreated HIV positive
  mothers.
• AZT to mothers reduces the risk of transmission
  to less than 8
• ART combined with cesarean section and a
  reduction in duration of ruptured membranes
  lessens risk to ? 2
• Risk of transmission is less when mothers are on
  triple therapy

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Babies born to HIV-positive Mothers

• Ideal regimen
• Mother should received combination therapy
  beginning at 28 wks
• Haitian MOH protocol, similar to Thai protocol
• Mother receives twice daily AZT from 36 weeks
• Infant receives single dose NVP and 1wk of AZT
• HIV-antibody testing at birth, 6, 12, and 18
  months
• If virologic testing is available, it should be
  done at 3 and 6 weeks of life to confirm the
  diagnosis

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General Health Care for Children Born to HIV
positive mothers

• Nutritionrecommend breast milk substitution
• Vitamin A 100,000 IU of Vitamin A at 9 months of
  age and 200,000 IU of Vitamin A every 6 months
  for the first 5 years of life
• Monthly exam with height, weight
• All infant vaccinations should be given
• Co-trimoxazole prophylaxis from 6 weeks of life
  until proven HIV negative

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Babies born to HIV positive mothers should have
close monitoring and nutritional support

• Even HIV negative babies have a higher risk of
  death.
• Transmission through breast milk accounts for up
  to 30 of pediatric infections
• In countries where there is no access to clean
  water, formula feeding is dangerous as infants
  can die of diarrheal disease.
• If women are treated with highly active
  antiretroviral therapy the chance of transmission
  through breast milk is less.

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Breast feedingin HIV positive womenKenya,
randomized trial (JAMA 2001 Nov
21286(19)2413-20)

• Mothers were randomly assigned either to use
  formula (n 186) or to breastfeed (n 185)
• Two-year estimated mortality rates
  formula-feeding and breastfeeding were 20.0 vs
  24.4
• No difference in the incidence of diarrhea or
  pneumonia
• Infection with HIV-1 was associated with a
  9.0-fold increased mortality risk (95 CI,
  5.3-15.3).
• HIV-1-free survival at 2 years was significantly
  higher in the formula arm.

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Breast feeding risk and duration of breast feeding

• Study of 499/2375 HIV-1positive women who breast
  fed their infants (East Afr Med J 2001
  Feb78(2)75-9)
• Overall risk of breast milk HIV-1 transmission
  16
• 47 of HIV-1 infections were attributable to
  breast feeding. (among breast feeding infants)
• Breast milk transmission risk was 21 when breast
  fed ? 3 months and 13 when breast feeding lt 2
  months.
• 702 infants (in a separate analysis) with breast
  feeding beyond 3-6 months had a late postnatal
  risk of HIV transmission of 4

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Estimated number of children (lt15 years) newly
infected with HIV during 2003
Eastern Europe Central Asia 1 500
Western Europe lt 100
North America lt 100
East Asia 3 300
North Africa Middle East 8 400
Caribbean 6 000
South South-East Asia 47 000
Sub-Saharan Africa 550 000
Latin America 6 400
Oceania lt 300
Total 630 000
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Estimated deaths in children (lt15 years) from
AIDS during 2003
Eastern Europe Central Asia 900
Western Europe lt 100
North America lt 100
East Asia 2 000
North Africa Middle East 5 000
Caribbean 5 200
South South-East Asia 34 000
Sub-Saharan Africa 440 000
Latin America 5 600
Oceania lt 200
Total 490 000
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Diagnosing Pediatric Infection
-Difficult to know if the baby is HIV infected or
not -Transmission through breast milk accounts
for up to 30 of pediatric infections
Diagnosis ??
ELISA will be positive for 12-18 months
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HIV PCR Filter Paper Testing

• Picture
• Easily performed, stable for many months,
  non-infectious

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HIV PCR Filter Paper Testing
2 Negative PCR tests Infant is HIV NEGATIVE
2 Positive PCR tests Infant is HIV POSITIVE
1 Negative PCR test and 1 positive PCR test Repeat PCR test a 3rd time
If the infant has 1 negative PCR test 4 months Infant is HIV NEGATIVE
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Diagnosis Treatment in Children lt18 months
Diagnosis
ELISA will be positive for 12-18 months
Diagnostic test not available
Positive Virologic test
Symptomatic
Asymptomatic
Cotrimox. Prophylaxis 6 month or 1 year
Antibody at 12-15 mos ?Treat with HAART?
Not severely ill treat infections and defer HAART
AND
HAART if symptomatic
Retest ELISA at 18 months or if symptomatic
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Protocol 3.11 Initiation of ART in HIV-Positive
Children with or without CD4 Count
Child confirmed HIV by ELISA or rapid test at
15-18 months or viral load after 3 weeks of age

• WHO Pediatric Stage I disease defer ART
• Normal weight and height growth curves
• Normal development
• Asymptomatic

See Appendix B for clinical staging
CD4 count available?
No
Yes

• WHO Pediatric Stage II disease consider ART and
  TMP/SMX prophylaxis
• Falling off growth curves, mild weight loss by
  report or documented as 5-10
• Growth not reflecting nutritional support
• Thrush
• OIs or bacterial infections not responsive to
  treatment

Refer to Table 3.4 for diagnostic categories by
age-based CD4 percentage and total CD4 count
Category I Defer ART work up symptomatic
illnesses

• WHO Pediatric Stage III disease begin ART and
  TMP/SMX prophylaxis
• Wasting gt10, cachexia, or failure to thrive
• Recurrent OIs or life-threatening bacterial
  infections
• Severe neurologic complications
• Leukopenia, anemia, or thrombocytopenia

• Category II
• Consider ART and TMP/SMX prophylaxis if
• Occurrence of any OI
• Patient febrile or wasting, not due to TB or
  other etiology
• Mild weight loss by report or documented as 5-10

Category III Begin ART and TMP/SMX prophylaxis
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AIDS in Children, Start ART if Categories B or
CCategory B Moderately Symptomatic

• Pulmonary Tuberculosis
• Anemia (lt 8 gm/dL)
• Bacterial meningitis, pneumonia, or sepsis
• Candidiasis gt2 months in children aged gt6 months
• Diarrhea, recurrent or chronic
• Herpes simplex virus (HSV) stomatitis
• Herpes zoster (i.e., shingles) gt1 dermatome
• Fever lasting gt1 month
• complicated chickenpox

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AIDS in ChildrenCategory C Severely Symptomatic

•  Severe failure to thrive
• 0 for weight or symptoms of Kwashiorkor while
  receiving nutritional supplementation
• Developmental delay or loss of developmental
  milestones
• Severe forms of Tuberculosis
• refractory to treatment
• Neurologic abnormalities suggestive of
  intracranial infection
• New onset seizures
• Focal neuro exam
•  

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James, at 14, is our oldest living pediatric
patient, he started on HAART last year, he is
now healthy, goes to school and is an outstanding
student
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Table 3.4 HIV Pediatric ClassificationImmune
Categories Based on Age-SpecificCD4 and T-Cell
Count and Percentage
lt12 months lt12 months 1-5 years 1-5 years 6-12 years 6-12 years
Immune category cells/mm3 () cells/mm3 () cells/mm3 ()
Category I No suppression 1500 (25) 1000 (25) 500 (25)
Category II Mild suppression 750-1499 (15-24) 500-999 (15-24) 200-499 (15-24)
Category III Severe suppression lt750 (lt15) lt500 (lt15) lt200 (lt15)
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ART Regimens for Children

• First-line Regimen (same as adults)
• NRTIs (usually 3TC and AZT)
• NNRTI (usually NVP)
• Efavirenz should not be used in children less
  than 3 years old
• Questions have arisen regarding resistance if
  mothers have received multiple courses of single
  dose Nevirapine, mothers treatment regimen
  should be considered, but no studies to date.

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Table 3.5 Summary of ART Formulations and Doses
for Children
Drug Formulation(s) Pharmacokinetic data available? Age or weight, dose,b frequency
Zidovudine (AZT) Syrup 10 mg/ml Capsules 100 mg, 250 mg Tablet (may be divided and crushed) 300 mg All ages lt4 wks 4 mg/kg/dose 2x/day 4 wks to lt13 yrs 180 mg/m2 /dose 2x/day Maximum dose, gt13yrs 300 mg/dose 2x/day
Lamivudine (3TC) Oral solution 10 mg/ml Tablet (may be divided and crushed) 150 mg All ages lt30 days 2 mg/kg/dose 2x/day gt30 days or lt60 kg 4 mg/kg/dose 2x/day Maximum dose, gt60 kg 150 mg/dose 2x/day
Zidovudine/Lamivudine (AZT/3TC) No liquid available Tablet 300 mg AZT plus 150 mg 3TC Adolescents and adults Maximum dose, gt13 yrs or gt60 kg 1 tablet/dose 2x/day
Didanosine (ddI) Oral suspension pediatric powder/ water 10 mg/ml (in many countries, needs to be made up with additional antacid) Chewable tablets 25 mg, 50 mg, 100 mg, 150 mg, 200 mg Enteric-coated beadlets in capsules 125 mg, 200 mg, 250 mg, 400 mg All ages lt3 mos 50 mg/m2 /dose 2x/day 3 mos to lt13 yrs 90 mg/m2 /dose 2x/day or 240 mg/ m2 /dose qd Maximum dose, gt13 yrs or gt60 kg 200 mg/dose 2x/day or 400 mg qd
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Table 3.5 Summary of ART Formulations and Doses
for Children
Drug Formulation(s) Pharmacokinetic data available? Age or weight, dose,b frequency
Stavudine (d4T) Oral solution 1 mg/ml Capsules 15 mg, 20 mg, 30 mg, 40 mg All ages lt30kg 1 mg/kg/dose 2x/day 30-60 kg 30 mg/dose 2x/day Maximum dose, gt60 kg 40 mg/dose 2x/day
Nevirapine (NVP) Oral suspension 10 mg/ml Tablet (may be divided and crushed) 200 mg All ages 15-30 days of age 5 mg/kg daily for 2 weeks, then 120 mg/m2 2x/day for 2 weeks, then 200 mg/m2 2x/day gt30 days of age 120 mg/m2 2x/day for 2 weeks, then 200 mg/m2 2x/day Maximum dose 200 mg daily for 2 weeks, then 200 mg 2x/day
Efavirenz (EFV) Syrup 30 mg/ml (note syrup requires higher doses than capsules see dosing chart) Capsules (may be opened and divided) 50 mg, 100 mg, 200 mg gt3 yrs old Capsule (liquid) dose for gt3 yrs 10 to lt15 kg 200 mg (270 mg 9 ml) qd 15 to lt20 kg 250 mg (300 mg 10 ml) qd 20 to lt25 kg 300 mg (360 mg 12 ml) qd 25 to lt33 kg 350 mg (450 mg 15 ml) qd 33 to lt40 kg 400 mg (510 mg 17 ml) qd Maximum dose, gt40 kg 600 mg qd
a Adapted from World Health Organization.
Scaling up antiretroviral therapy in
resource-limited settings guidelines for a
public health approach. Geneva World Health
Organization, 200213-21. (Accessed June 4, 2004
at http//www.who.int/hiv/topics/arv/en/scaling_e
xe_summary.pdf.) b Meter2 body surface area
calculation square root of (height in
centimeters times weight in kilograms divided by
3600).
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Reasons for Changing Therapy

• There are multiple reasons which may lead to the
  temporary discontinuation of antiretroviral
  therapy, including
• Intolerable side effects
• Drug interactions
• Treatment failure

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Recommended second-line regimens

• ABCddI (or tenofovir) LPV/r
• Abacavir twice daily/Didanosine twice daily
  /Lopinavir/ritonavir (Kaletra)
• Alternatively the following regimen can also be
  used
• ABCddI (or tenofovir) SQV/r

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Considerations for selecting second line drugs

• The recommended second line is
• ABCddILPV/r
• LPV/r is not recommended in TB
• LPV/r and SQV/r require refrigeration
• ddI should NOT be taken with food
• LPV/r should be taken with food

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Pediatric HIV Summary

• Children are infected in utero, at birth or
  during breast feeding
• Antibody will be falsely positive in babies born
  to HIV positive mothers for up to 18 months
• Virologic test is necessary to confirm the
  diagnosis prior to 12 months (Culture, PCR, DNA)
• Children who are confirmed to HIV infected can be
  started base on clinical symptoms or age
  dependent CD4 count

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Mesi anpil
Gracias