Updates Recommendation on
Prevention of Mother-to-Child
HIV Transmission in Indonesia
Dina Muktiarti
Department of Child Health Faculty of Medicine Universitas
Indonesia – Cipto Mangunkusumo Hospital/
HIV Task Force Indonesian Pediatric Society
Outline
• Background
• Pediatric HIV transmission
• Management of baby born from HIV infected mother
• IDAI Recommendation on Prevention Mother-to-Child
Transmission
HIV PEDIATRIC CASES IN INDONESIA
(2010-2016)
1.200
1.030
1.000
903
795
800 759
600 547 541 ≤4 years
405 5-14 years
390 406
400 358 338
316
242 208 TOTAL: 7238
200
(3.65% from
0 all HIV cases
2010 2011 2012 2013 2014 2015 2016 in Indonesia
TOTAL 795 789 749 1075 1388 1133 1309
Indonesia Ministry of Health, 2017
THAILAND
Mother to child transmission of HIV
Postpartum through
Intrauterine Delivery
breastfeeding
5-10% 10-20%
5-20%
Only 9% HIV-infected pregnant mother on ART
out of 250,000 in Indonesia Role of
All risk without breastfeeding : 15-30% pediatrician
Risk with 6 months breasfeeding : 25-35 %
Risk with 18-24 months breastfeeding : 30-45% JAMA 2000;283:1175–82
WHO, 2006
Importance of timing for PMTCT
HAART <4 weeks for HIV-infected
pregnant women had a 5.5-fold
increased risk of HIV transmission
compared with HAART >13 weeks
Chibwesa CJ, et al. JAIDS 2011;58:224-8.
Management of infants born from HIV-
infected mother
Co-
Selection of ARV
trimoxazole
nutrition prophylaxis
prophylaxis
Early infant
Immunization
diagnosis
SELECTION OF NUTRITION
Selection of nutrition for infants
born from HIV-infected children
Breastfeeding
Formula feeding
Advantages vs Disadvantages
Risk Factors of HIV MTCT Through
Breastfeeding
• Viral load level in blood (> 1000
copies) and breastmilk
Mother • Maternal CD4
• Breast problem
• Gut integrity
Infant • Nutrition choice
Risk of transmission according to nutrition
45
40
Mixed feeding
35 Exclusive breastfeeding
30 Formula feeding
25
20
15
10
5
0
AIDS. 2001;15:379-87
Consequences of giving breastmilk from HIV
infected mother to their infants
Mothers/infants’ health
ART Resistance
HIV MASHI study (Africa):
• Mortality at 7 months old:
transmission formula feeding higher • Infants who who were
compared to breastfeeding exposed with ART on
HIV transmission infants.
• Mortality at 18 months old:
PMTCT have high
rate through BF
no difference risk for ART
despite of maternal RSCM: resistance (30-80%),
and child ART: 5- • no significant morbidities
especially with
10% and mortalities in formula
feeding infants nevirapine
Chikhungu , et al (meta-analysis)
JAMA. 2006;296:794-805
Zeh C, et al. PLoS Med. 2011; 8: e1000430.
Nelson JA, et al. AIDS. 2015;29:2131-8.
Fogel JM, et al. Pediatr Infect Dis J. 2013; 32: 10.
AFASS Principle of Formula Feeding
Acceptable Feasible Affordable
If AFASS requirement for formula feeding are
not fulfilled, babies should be given
exclusively breastfeeding for 6 months.
Safe Sustainable
Counselling is important!
IDAI Recommendation
• Nutrition for infants born from HIV infected mother is formula
feeding to avoid further HIV transmission.
Level of evidence 1a, recommendation A
• Mixed feeding should be avoided because this method has the
highest risk for HIV transmission.
Level of evidence 1b, recommendation A
ANTIRETROVIRAL PROPHYLAXIS
ARV Prophylaxis (WHO)
High risk infants Low risk infants
Breastfeeding AZT + NVP 12 weeks NVP 6 weeks
Formula feeding AZT + NVP 6 weeks AZT or NVP 6 weeks
High risk infants are defined as those:
• born to women with established HIV infection who have received less than four weeks of
ART at the time of delivery; or
• born to women with established HIV infection with viral load >1000 copies/mL in the four
weeks before delivery, if viral load measurement available; OR
• born to women with incident HIV infection during pregnancy or breastfeeding; OR
• identified for the first time during the postpartum period, with or without a negative HIV test
prenatally.
Outcome of infants exposed to ART during PMTCT
program
• Zeh, et al found HIV drug resistance mutations in HIV-infected infants most likely
because of exposure to maternal ARV drugs through breastmilk.
• ART resistance: 30% (6/20) at 6 weeks, 63% (14/22) at 14 weeks, and 67%
(16/24) at 6 months post partum.
• Resistance to lamivudine (81%) and nevirapine (40%)
Consequences of NVP resistance is to change NVP to
• Nelson, et al:
lopinavir/ritonavir. However, we do not have LPV/rtv in
• HIV-infected infants in the infant-NVP arm were significantly more likely to
have NVP resistance thanpediatric
infected formula.
infants in the other two arms of the trial,
especially during breastfeeding through 28 weeks of age
• 56% in infant-NVP arm vs. 6% in maternal-antiretroviral arm and 11% in
control arm
• Fogel, et al:
• 75% infants who were exposed with nevirapine on PMTCT program, have
resistance to NVP (RR 12.8) Zeh C, et al. PLoS Med. 2011; 8: e1000430.
Nelson JA, et al. AIDS. 2015;29:2131-8.
Fogel JM, et al. Pediatr Infect Dis J. 2013; 32: 10.
IDAI Recommendation
ARV prophylaxis for infants born from HIV infected
mother:
• Formula feeding infants: zidovudine for 6 weeks
• Breastfeeding infants: zidovudine and nevirapine for 6
weeks (as long mother on ART)
Level of evidence 1a, recommendation A
Dose of ARV prophylaxis
Dose Duration
≥35 weeks’ gestation at birth: 4 mg/kg/dose PO twice daily, started
as soon after birth as possible and preferably within 6–12 hours of
delivery
≥30 to <35 weeks’ gestation at birth: 2 mg/kg/dose PO started as
soon after birth as possible, preferably within 6–12 hours of
Zidovudine Birth through
delivery, then every 12 hours, advanced to 3 mg/kg/dose PO every
6 weeks
12 hours at age 15 days
<30 weeks’ gestation at birth: 2 mg/kg body weight/dose PO started
as soon after birth as possible, preferably within 6–12 hours of
delivery, then every 12 hours, advanced to 3 mg/kg/dose PO every
12 hours after age 4 weeks
Birth weight 1500–2000 gram: 8 mg/dose
Nevirapine Birth through
Birth weight 2000-2499 gram: 10 mg/dose
6 weeks
Birth weight > 2500 gram: 15 mg/dose
CO-TRIMOXAZOLE PROPHYLAXIS
Co-trimoxazole Prophylaxis
WHO, 2010
IDAI Recommendation
• Co-trimoxazole prophylaxis should be given to all
infants born from HIV-infected children since 6 weeks
old until HIV infection is excluded.
Level of evidence 2b, recommendation B
EARLY INFANTS DIAGNOSIS
HIV diagnostic tools
Testing Specimen Purpose Pediatric Comments
method/ type/ population
assay modality for
testing
HIV Whole Diagnostic Children >18 The nationally defined
serology blood months of age serial 2- or 3-test
algorithm should be
followed.
HIV DNA Whole Diagnostic Infants and Confirm reactive result
blood/ children with a second
Liquid/DBS virological test.
HIV RNA Plasma/ Diagnostic Infants and Exercise caution in
liquid children interpreting negative
Whole results if infant is
blood/DBS established on ART.
Confirm reactive result
with a second virological
test.
Timing of detectable HIV antibody and RNA HIV in HIV exposed infants
Early Infants Diagnosis
• Virology examination (PCR RNA/DNA HIV) should be done in all infants in PMTCT
program at 6 weeks old or as soon as possible after that.
Level of evidence 1b, recommendation A
• Infants who has positive virology test, cART should be given and on the same time
second blood sample should be taken to confirm the diagnosis.
Level of evidence 1b, recommendation A
• Infants who has negative virology test on their first examination, should repeat the
virology test at 4-6 months old to confirm the diagnosis.
Level of evidence 1b, recommendation A
• Diagnostic test to confirm diagnosis can be done at 18 months old with serology test.
Level of evidence 1b, recommendation A
IMMUNIZATIONS
IMMUNIZATIONS FOR HIV INFECTED CHILDREN
BCG Vaccine
• Hesseling AC, et al:
• Retrospective review of culture-confirmed BCG disease in children
<13 years of age:
• Among 25 children, 88% had local disease, 32% had distant or
disseminated disease, and 20% had both.
• 17/25 children were HIV-infected
• All eight children with distant or disseminated disease were
severely immunodeficient
• Mortality rate in this group was 75%.
• The risk of disseminated BCG in HIV-infected infants in the South African
context to be between 329 and 417 per 100 000 vaccine recipients.
• South African and Thai cohort:
• BCG-IRIS: 3–14.8% Hesseling AC, et al. Clin Infectious Dis. 2006;42(4):548–58.
Nuttal JJC, et al. Tuberc Res Treat. 2011; 2011: 712736.
Immunizations
• Inactivated vaccine can be given for babies born from HIV-
infected mother according to national immunization schedule.
Level of evidence 1b, recommendation A
• BCG vaccine can be given to babies born from HIV-infected
mother if the babies already proven not infected with HIV.
Level of evidence 1b, recommendation A
• Measles and oral polio vaccine can be given to healthy babies
born from HIV-infected mother
Level of evidence 1b, recommendation A
IDAI Recommendation
ARV
• Formula Prophylaxis
feeding to • CTX: 6 Diagnosis
avoid further • Formula weeks old • IDAI/Kemenkes
transmission feeding • PCR schedule
until HIV
• No mixed infants: AZT RNA/DNA at 6 • Precaution for BCG
feeding for 6 weeks infection is
excluded. weeks old and
• Breastfeeding 4-6 months old
infants: AZT Co-
Nutrition Immunization
and NVP for 6 trimoxazole
weeks
PMTCT Schedule
Born 10 days 4 weeks 6 weeks 2 mos 3 4 6 9 18
mos mos mos mos mos
Body weight/
body height
Nutrition* FF FF FF FF FF FF FF FF-SF FF-SF FF-SF
ARV prophylaxis
Zidovudin 4 mg/kg/dose,
2 times/day
Co-trimoxazole
4-6 mg TMP/kg/dose,
once daily**
Immunizations According to Ministry of Health/Indonesian Pediatric Society schedule
Special precaution: BCG
Hb/Ht *with indication
PCR RNA/DNA
1 2 AB
Abbreviations: FF: formula feeding; SF: solid food; Hb: Hemoglobine; Ht: Hematocrit; PCR RNA/DNA : Polymerase chain reaction RNA/DNA ; AB: HIV antibody; ARV:
antiretroviral.
* : If AFASS requirement for formula feeding are not fulfilled, babies should be given exclusively breastfeeding for 6 months.
** : ARV prophylaxis for babies with formula feeding: zidovudine
ARV prophylaxis for babies with breastfeeding: zidovudine and nevirapine.
Special dose for premature babies.
THANK YOU
