A to Z in HIV Exposed Infant

Management
Endah Citraresmi
Satgas HIV IDAI
PKIAN RSAB Harapan Kita
Agenda
HIV infection in children – why it differs from adults

HIV transmission in children

Prevention of Mother-to-Child HIV Transmission

• Infant feeding
• ARV prophylaxis
• PCP prophylaxis
• Early infant diagnosis
• Immunization

HIV exposed but uninfected infant

HIV infection in children
HIV infection in children has a unique / difference compared
to infection in adults
The progress of
Causes impaired Not all HIV drugs
severe disease Higher growth and are available for
occurs faster 🡪 the mortality rate development children in
immune system is
immature when Indonesia
infection occurs

Must be prevented, and very preventable!

Hypothetical Model of Vertical Transmission in Children

Rapid 20%
clinical manifestations from several
months of age, rapidly worsening

Intermediate 70%
manifestations at the age of 2-5
years, generalized lymphadenopathy,
hepatosplenomegaly, bacterial
infections

Slow 10%
mild manifestations in childhood,
asymptomatic and accidentally
detected

Shearer and Hanson: Medical Management of AIDS in Children, 2003

Pediatric HIV Cases in Indonesia 2010-2021

Number of cases of HIV-infected children (0-14 years) in Indonesia

Kementrian Kesehatan Indonesia, 2021
HIV transmission in children

• Acquisition of HIV in children and youth can occur through:

Other mechanisms
Mother-to-child
(“non-vertical,
transmission (MTCT) Sexual contact
non-sexual”):
(~90%)
unsafe injection
practices
Transmission of HIV from Mother to Child

Intrauterine Intrapartum Breastfeeding

If we do nothing ..

JAMA 2000, 283(9), 1175–1182

Mother-to-child transmission (MTCT)

Increase the risk of

Maternal risk factors transmission during Postnatal risks
delivery
• Acute HIV infection • Mode of delivery • Mixed infant feeding
during pregnancy • Premature delivery • Maternal mastitis
• Detectable plasma • Duration of • Practices such as
viral load membrane rupture premastication or
• Low CD4 count >4 h prechewing of food
• Advanced stage of • Inflammation in the fed to infants
HIV infection birth canal
Prevention of Mother to Child HIV
Transmission (PMTCT)
Care of the infant begins way before the infant’s birth

postnatally
in utero during during labor
through
pregnancy, and delivery,
breast-feeding

routine use of cART cesarean delivery when provision of neonatal MTCT risk can
during pregnancy to maternal viral load is antiretroviral be reduced to
maximally suppress viral not maximally prophylaxis and <1%
load suppressed avoidance of
breast-feeding
Pediatrics 2012;129:e74–e81
Prevention
of
Mother-to-C
hild HIV
Transmission
(PMTCT)
 • Adequate maternal history to evaluate maternal
co-infection
• Feeding choice
When a • Antiretroviral perinatal transmission prophylaxis
• Monitoring for toxicity from in utero and neonatal
Neonate is ARV drug exposure and monitoring for and
Born to a HIV management of short-term toxicity during infant ARV
prophylaxis
Positive • Counseling of parents
Mother • Immunizations
• Pneumocystis Jirovecii Pneumonia (PCP) prophylaxis
• Growth monitoring
• Determination HIV status in HIV exposed children
Infant Feeding

Breastfeeding Formula Feeding

Advantages Cheap No risk of HIV transmission
Prevents morbidity and mortality from Does not depend on mothers' health
infectious diseases

Disadvantages Risk of HIV transmission (minimized by
maternal ARV treatment & infant
prophylaxis)
Requires lactation counselor assistance to
prevent mastitis/cracked nipples
Depends on mothers’ health
Guidelines WHO, UNICEF
Developing countries in Africa & Asia
Costly and not readily available
No maternal antibodies
Needs clean water and clean supplies
🡪 risk of malnutrition, infectious
(pneumonia, diarrhea) diseases
Developed countries in US (CDC), Europe
(BHIVA, PENTA) & Australia
Asia: Thailand, Malaysia
Close to Zero, but Not Zero
2431 mother-infant (breastfeeding)
pairs – randomized into mART arm
& iNVP arm
• 7 confirmed infant HIV-1
infections in each treatment arm
• 2 infants in mART treatment arm
infected despite non-detected or
<40 copies maternal VL

Maternal plasma HIV-1 viral load

and infant NAT testing of two
infants with maternal HIV-1 VL
non detected or detected but
below 40 copies/mL prior to
positive infant HIV-1 NAT testing

Flynn, et al. JAIDS Journal of Acquired Immune

Deficiency Syndromes 88, no. 2 (October 1, 2021):
206–13.
Cumulative probability of detecting HIV infection over time
according to method of feeding

Mixed feeding

Breastfeeding

Formula feeding

Coutsoudis, et al. AIDS 15, no. 3 (February 2001): 379–87

Indonesian Pediatric Society 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
AFASS

Acceptable
• Replacement feeding for breast milk is acceptable by the mother, the family and others who are close to the family

Feasible
If AFASS requirement for formula feeding are not
• The mother has access to clean and safe water for cleaning the feeding bottles, teats, measuring cup and spoon, and
diluting the formula milk if it comes as a powder

Affordable
fulfilled, babies should be given exclusively
breastfeeding
• The family can afford to buy enough formula milk or animalfor
milk6
to months
feed the baby adequately

Sustainable
• The mother is able to prepare feeds for the child as frequently as recommended and as the baby demands

Safe
• The formula milk should be safe and nutritious for the health of the baby
ARV Prophylaxis (WHO 2016, 2021)

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.

Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring: Recommendations for a Public
Health Approach. Geneva, Switzerland: World Health Organization, 2021.
Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring: Recommendations for a Public
Health Approach. Geneva, Switzerland: World Health Organization, 2021.
Antiretroviral Management of Newborns with Perinatal HIV Exposure or
HIV Infection – US CDC Guidelines (2023)

Level of Perinatal
HIV Transmission Description Neonatal ARV Management
Risk
Low Risk of Infants ≥37 weeks gestation when the mother— ZDV for 2 weeksa
Perinatal HIV • >10 weeks of ART during pregnancy and
Transmission • VL <50 copies/mL at least 2 consecutive tests (min
4 weeks apart) for the duration of pregnancy, and
•VL <50 copies/mL at or after 36 weeks and within 4
weeks of delivery, and
•No acute HIV infection during pregnancy, and
•Good ART adherence
Infants born to mothers who do not meet the ZDV for 4 to 6 weeksa
criteria above but VL <50 copies/mL at or after 36
weeks gestation
Premature infants (<37 weeks gestation) who are ZDV for 4 to 6 weeksa
not at high risk of perinatal acquisition of HIV
Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States.
Department of Health and Human Services. 2023. Available at https://clinicalinfo.hiv.gov/en/guidelines/perinatal.
 Level of Perinatal
HIV Transmission Description Neonatal ARV Management
Risk
High Risk of Mothers who did not receive antepartum ARV Presumptive HIV therapy:
Perinatal HIV drugs, or ZDV+3TC+NVP (treatment
Transmissiona,b Mothers who received only intrapartum ARV dose) or ZDV+3TC+RAL
drugs, or administered together from birth for
Mothers who received antepartum ARV drugs but 2 to 6 weeks; if the duration of the
did not have viral suppression (defined as at least 3-drug regimen is shorter than 6
two consecutive tests with HIV RNA level <50 weeks, ZDV should be continued
copies/mL obtained at least 4 weeks apart) within 4 alone, to complete a total of 6
weeks prior to delivery, or weeks of prophylaxisd
Mothers with acute or primary HIV infection during
pregnancy or breastfeeding (in which case,
breastfeeding should be immediately
discontinued)c
Presumed Mothers with unconfirmed HIV status who have at ARV management as described
Newborn HIV least one positive HIV test at delivery or above for newborns with a high risk
Exposure postpartum, or of perinatal HIV acquisition 🡪
Mothers whose newborn has a positive HIV discontinued immediately if
antibody test supplemental testing confirms that
the mother does not have HIV.
Newborn with HIVe Positive newborn HIV virologic test/NAT Three-drug ARV regimen using
ARV Prophylaxis for Infants – Indonesian
Pediatric Society

Prophylaxis of ARV for infants born to HIV-infected mothers:

• Infants with formula milk: zidovudine for 6 weeks
Infants with breast milk: zidovudine AND nevirapine for 6 weeks
(and the mother should get ARV therapy)

Level of evidence 1a, recommendation A

21
 ARV Prophylactic Dosage
Dose Duration of
administration
Gestational age ≥35 weeks: 4 mg/kg/x, every 12 hours, can be started at
6-12 hours of age
Born to 6
Zidovudine Gestational age ≥30 to <35 weeks: 2 mg/kg/x, every 12 hours, then 3
weeks of age
mg/kg/x every 12 hours at age 15 days
Gestational age <30 weeks: 2 mg/kg/x, every 12 hours, then 3 mg/kg/x
every 12 hours after 4 weeks of age
Nevirapine Birth weight 1500–2000 grams: 8 mg/dose
Birth weight 2000-2499 grams: 10 mg/dose Born to 6
(for
Birth weight ≥ 2500 grams: 15 mg/dose weeks of age
breastfed
infants)

The latest time of administration of prophylactic ARV is 72

hours of age
 Most cases of Pneumocystis Jirovecii
PCP Prophylaxis Pneumonia (PCP) among HIV infected children
occur in the first-year of life. Peak incidence:
3-6 months; CFR: 40-90%

• Antimicrobial prophylaxis is very effective in preventing PCP

• All infants born to HIV infected women should be started on PCP prophylaxis at
4-6 weeks of age
• Cotrimoxazole prophylaxis: safe, inexpensive and highly effective
• Dose: 4-6 mg TMP/kg BW, 1x/day, every day

Infants who are at first identified as being HIV-exposed after 6 weeks of age should be started on
prophylaxis at the time of identification
PCP prophylaxis should not be administered to infant <4 weeks of age:
• low risk for PCP
• risk of adverse drug effects resulting from immature bilirubin metabolism; could also exacerbate
anemia in infants receiving zidovudine prophylaxis
Early Infant Diagnosis (EID)

•Early diagnosis is important to

provide early initiation of ARV
therapy
Early initiation of ARV therapy
gives a better clinical prognosis
HIV Testing in Infants
• Maternal HIV antibodies can be
transferred to the fetus through the
placenta. It disappears only at the age of
about 12-18 months
HIV antibodies (rapid test, ELISA) cannot
be used as a diagnostic tool in children
<18 months
Using PCR RNA HIV/viral load: expensive,
only available in big cities.
PCR DNA HIV 🡪 can use filter paper
(dried blood spot)
 HIV Testing in PMTCT Program

6 weeks old: 4-6 months old: 18 months old:

HIV PCR HIV PCR HIV Antibody

HIV task force, Indonesia Pediatric Society

Immunization
• Routine immunizations should be given to all HIV exposed children
according to the schedule
• At birth and the baby is in good health: Hepatitis B0 & Polio0
Regardless of whether the baby has received a PMTCT program, BCG
immunization can be given if the baby has been subjected to a
virological examination at the age of 6 weeks with a negative result
• If it is not possible to conduct a virological examination at the age of 6 weeks,
BCG can be given as long as the baby is in good health
If a rapid local reaction arises in the first week after BCG immunization, a
follow-up examination is carried out for the diagnosis of tuberculosis
 Indonesian Pediatric Society Recommendation

ARV
• Formula Prophylaxis
feeding to avoid • CTX: 6 weeks Diagnosis
further • Formula • IDAI/Kemenkes
old until HIV
transmission feeding infants: • PCR RNA/DNA schedule
AZT for 6 weeks infection is
• No mixed at 6 weeks old • BCG*
feeding • Breastfeeding excluded.
and 4-6 months
infants: AZT and old
NVP for 6 Co-trimoxazol
Nutrition Immunization
weeks e
Children affected by HIV

Children with
Children who are
Children living with caregivers or
exposed to HIV and
HIV household members
uninfected
living with HIV

HIV exposed uninfected = HEU

2020: 1.8 million children <15 2020: 15.4 million children born to
years women living with HIV who did not
acquire perinatal HIV

Nurturing care for children affected by HIV. WHO & UNICEF. 2020
HIV exposed but uninfected (HEU) infant

Clin Exp Immunol. 2014;176:11–22.

 Slogrove, Amy L. “It Is a Question of Equity:
Time to Talk about Children Who Are
HIV-exposed and ‘HIV-free.’” Journal of the
International AIDS Society 24, no. 11
(November 2021)

stillbirth,
fetal growth
restriction and
preterm birth

more often sickly and

not surviving as
expected compared to
children born to women
The package of risks for suboptimal early childhood health and without HIV
development in children who are HIV-exposed and HIV-free
Compared to children who are
HIV-unexposed with similar conditions at
birth
Preterm infants Fetal growth restriction

• higher rates of neonatal • do not catch up their

mortality, require growth deficits during
neonatal ICU 2x higher, the first year of life
experience worse infant
cognitive & motor
developmental outcomes
Compared to children who are HIV
unexposed:

Require hospitalization 2-3x more

often in early childhood 🡪 due to
Falling behind on expected early
infectious diseases: viral and
neurodevelopmental milestones,
bacterial respiratory tract
particularly in speech and
infections, invasive pneumococcal
language development
and group B Streptococcal
infections, diarrheal disease

Labuda SM, et al. Clin Infect Dis. 2020;71(2): 332–9.

Anderson K, et al. AIDS. 2021;35:2327–39
Wedderburn CJ, et al. Lancet Child Adolesc. 2019;4642(19):4–6.
 Incidence Rate and Total Rate of All-Cause Inpatient Admission, Inpatient
Admission With Infectious Diagnosis, and Mortality in the First 2 Years of Life,
Among Human Immunodeficiency Virus (HIV)–Exposed Uninfected Versus
HIV-Unexposed Uninfected Children

Labuda SM, et al. Clin Infect Dis. 2020;71(2): 332–9

Take Home Messages
• HIV infection in children, especially those transmitted from mother to
baby, can be prevented by conducting Prevention of Mother-to-Child
HIV Transmission (PMTCT) program
The PMTCT starts long before the baby is born
Proper management (infant feeding options, ARV prophylaxis, PCP
prophylaxis, early diagnosis of infants) can reduce the risk of MTCT to
<2%
The population of children born to HIV-infected mothers but not
infected (HIV exposed uninfected, HEU), is increasing and has its own
problems 🡪 should receive special attention