HIV IN CHILDREN

Dr JD Kabamba
OBJECTIVES

• Discuss the epidemiology of HIV in children in Zambia

• Describe the pathophysiology and natural history of perinatal HIV infection

• Describe the age-appropriate diagnostic tests for infants and children

• Describe the WHO clinical staging of HIV infection in children

• Discuss the approach to clinical diagnosis

Epidemiology of paediatric HIV Zambian
120
Percentage of HIV positive children who
are living with HIV who either know
their HIV status, on ART or virally…

100 • HIV type 1 Group M, subtype C

100
93.2
80 • Estimated children living with HIV in
80.7 Zambia: 77,631
60
60.5 • Estimated number with known HIV
status: 46,968
40

• Estimated on treatment: 43, 765

20

• Virally suppressed: 35, 312

0
Know Virally
Current
PLHIV HIV+ Suppress
on ART (Source MOH, 2021 )
status ed
Children 100 60.5 93.2 80.7
 Factors contributing to high HIV prevalence in children
1. High HIV prevalence (11.1% 15-49 years old) in Zambia
(2018 ZDHS)
2. High prevalence of infection in women of childbearing age at 14.2%
(ZDHS, 2018)
3. HIV Prevalence among young women (15 – 24 years) 6% (ZDHS 2018)
4. Low coverage of facility delivery 84% (ZDHS 2018)
5. Lack of male partner involvement in ANC
6. Late booking for ANC
7. Low retesting of HIV negative PBFW
8. Stigma
 Modes of HIV transmission in children
• 95% of infected infants
• Mother to child transmission (MTCT)
• 5% of infected infants
• Sexual transmission (adolescents/abuse)
• Transfusion of infected blood and its products
• Unsterile injection procedures
• Scarification and other traditional practices
Mother-to-child transmission rates without intervention

• Pregnancy ---------- (5 - 10%)

• Delivery ------- (10 -20%)

• Breastfeeding ----- (5 – 20%)

6
Risk Of Transmission Of HIV- Time of testing
30-40% HIV
exposed children
become infected

5% intrauterine
NAT +ve first week
of life

10-20% during
delivery
NAT +ve by age 6
weeks

10-20% via
breastfeeding
Do NAT at 6 wks
after stopping BF
7
Pathophysiology and natural history
Immunologic Parameters in Children
Immunologic Parameters in Children
Effect of HIV on the immune system

• CD4+ T-lymphocytes coordinate immune function of:

• the non-specific immune cells
• the specific CD8+ and B-lymphocytes

• HIV targets CD4+ T-lymphocytes and destroys them

• HIV causes profound immunodeficiency as a result of depletion of CD4+ T-lymphocytes.

• This is the hallmark of HIV infection

• The CD4+ T-lymphocyte dysfunction is two-fold:

• Reduction in numbers
• Impairment in function
Immunological defects caused by HIV

Other defects caused by HIV on immune function include:

• Lymphoid tissue destruction
• CD8 cell dysfunction
• B Cell abnormalities
• Thymic dysfunction
• Autoimmune abnormalities
Immunologic Parameters

• CD4 count/percentage declines with disease progression

• Rapid increases in risk of developing AIDS or death as CD4+ cell

percentage decreases below 15–20%

• Prognosis poorer in infants <12 months than in older children

Natural History - Viral load (HIV RNA) In Children

• This pattern is due to inability of the infant’s immature immune

system to contain viral replication

• There is also a greater number of HIV susceptible cells

• High RNA levels and low CD4 counts (<15%) independently predict
increased risk of progression to AIDS and death
Natural History - Viral load (HIV RNA) In Children

• Viral load in perinatally infected infants differs from infected adults

• In Infants:
• Viral load levels are low at birth
• Increase to high levels > 100,000-millions of copies/ml by 2 months of age
• Remain high throughout the first year of life
• Decline slowly over the next few years to “set point”
Typical Immune Response
Slow decline over 24 mo
Natural history :
Clinical disease progression without treatment

Category 1 (25 – 30%): Rapid progressors

• Rapid disease progression; infants die within 1 year
• Disease acquired in-utero or perinatally
Category 2 (50 – 60%): Slow progressors
• Children who develop symptoms early in life
• Deteriorate and die by 3 to 5 years
Category 3 (5 – 25%): Long-term survivors
• Long-term survivors who live beyond 8 years of age
Clinical presentation of rapid progressors

Early Severe Form Characterised by:

• LBW
• Early stunting
• Developmental delay
• Persistent oral candidiasis
• Recurrent/persistent diarrhoea
• Recurrent bacterial/fungal infections
• Hepato-splenomegaly
• Severe encephalopathy before 18 months
• High viral load at birth
• Rapidly decreasing CD4 counts
Clinical presentation of slow progressors

• Opportunistic Infections after 2 - 10 years

• Growth stunting common
• Lymphoid interstitial pneumonitis (LIP)
• Parotitis
• Recurrent bacterial and fungal infections
• Skin problems
• AIDS related cancers
• Low viral loads at birth, stable CD4 counts for 2 - 10 years then slow
decline
Clinical presentation of long-term survivors

• Remain asymptomatic until 8-10 yrs and thereafter, start to

present with clinical symptoms suggestive of HIV infection
Laboratory diagnosis

• Maternal HIV antibodies are passively transferred to infant across the placenta

• Maternal antibodies wane with time (over 6-24months)

• Antibody tests are positive at birth in MOST children born to HIV infected women,
including those children that are NOT HIV infected

• Antibodies in an HIV infected child develop 6 to 12 weeks from the time the child
gets infected

• In an HIV positive child <24 months the child COULD have both its own and the
maternal anti-bodies
Laboratory diagnosis

• The definitive diagnosis of HIV infection in children at any age

requires diagnostic testing that confirms the presence of HIV
• Children < 24 months: Virologic testing- Nucleic Acid Test (NAT)

• Children ≥ 24 months: Antibody testing (Screening Test : Determine HIV 1/2;

Confirmatory : SD Bioline HIV-1/2)
Laboratory diagnosis

• Initial virological testing at Birth; if missed, test at first contact, then at 6 weeks
age
• Testing at 6 weeks identifies the vast majority of infants infected in utero and
intrapartum
• Delaying testing beyond this time delays diagnosis and puts HIV infected infants at
risk for disease progression and death
• Testing earlier than 4-6 weeks of age may be less sensitive for cases of peripartum
transmission
• Positive test results should be fast-tracked to the mother-baby pair for prompt ART
initiation
Laboratory diagnosis

For the well, non-breast fed infant

Do NAT at birth or first contact.
• If negative, retest NAT at 6 weeks.
• If negative at 6 weeks, do serologic test at 24 months

For a breast-feeding child

• NAT should be done at birth or first contact, 6 weeks, 6 months and 9
months of age
• If the initial NAT is positive:
• Initiate ART and retest NAT immediately to confirm infection
• Antibody test at 12, 18 and 24 months
• If tests positive in < 24 months, follow up with NAT
Last serology test should be at least 6 weeks after breastfeeding cessation

Integrate HIV testing with EPI visits

Preventing paediatric HIV infection
Management of HIV-Exposed Infant (prophylaxis)
Presumptive Diagnosis of Severe HIV Disease in Infants and Children <24
Months of Age
Presumptive diagnosis of severe HIV disease should be made if:
1. The child is confirmed as being HIV antibody-positive
2. The infant is symptomatic with two or more of the following:
 Oral thrush
 Severe pneumonia
 Severe sepsis
 A diagnosis of any AIDS-indicator condition(s)

3. Other findings that support the diagnosis of severe HIV disease in an HIV-seropositive infant
include:
 Recent HIV-related maternal death or advanced HIV disease
 Child’s CD4% <25%

Antiretroviral therapy should be started without delay!

Confirm the diagnosis of HIV infection as soon as possible using age-appropriate tests
WHO Clinical Staging for Infants and Children

Importance of staging:

• Provides a guide to prognosis and interventions needed at the

different stages (including indications for changing ART)

• Provides guidance in monitoring response to therapy (treatment

failure or improvement).

The Zambia Paediatric ART Training

30
Curriculum
WHO Clinical Staging for Infants and Children
Stage 1
• Asymptomatic
• Persistent Generalised Lymphadenopathy (PGL)
Stage 2
• Skin:
Herpes zoster
Extensive warts
Papular pruritic eruptions (itchy rash)
Fungal nail infections
Extensive molluscum contagiosum
• Unexplained persistent hepatosplenomegaly
• Recurrent or chronic upper respiratory infections
• Recurrent oral ulcerations
• Unexplained persistent parotid enlargement
• Linear gingival erythema
• Unexplained extensive dental caries
WHO Clinical Staging for Infants and Children
Stage 3 Blood:
Unexplained anaemia (<8g/dl)
• Unexplained moderate malnutrition not
adequately responding to standard therapy (-2 SD) neutropenia (<0.5 x 109 /l
chronic thrombocytopenia
• Unexplained persistent fever (above 37.5 > 1/12)
(<50 x 109 /l)
• GIT:
Unexplained persistent diarrhoea (>14 days)
Persistent oral candidiasis (after first 6/52 of life)
Oral hairy leukoplakia
Acute necrotising gingivitis/periodontitis
• RS :
Pulmonary TB
Severe recurrent presumed bacterial pneumonia
Symptomatic lymphoid interstitial pneumonitis
(LIP)
Chronic HIV-associated lung disease including
bronchiectasis
Lymphnode TB
WHO clinical staging for Infants and Children:
Stage 4
• Unexplained severe wasting, stunting or
severe malnutrition not responding to
standard therapy
• Pneumocystis jirovecii pneumonia
• Recurrent severe bacterial infections
• Chronic herpes simplex infection;
(orolabial or cutaneous of more than one
month duration or visceral at any site)
• Extrapulmonary TB
• Kaposi sarcoma
• Oesophageal candidiasis (or Candida of
trachea, bronchi or lungs)
• CNS toxoplasmosis (outside the neonatal
period)
• HIV encephalopathy
• CMV infection; retinitis or infection affecting
another organ, with onset at age more than one
month.
• Extrapulmonary cryptococcosis including
meningitis
• Disseminated endemic mycosis
(extrapulmonary histoplasmosis,
coccidiomycosis)
• Chronic Cryptosporidiosis with diarrhoea
• Chronic Isosporiasis
• Disseminated non-tuberculous mycobacteria
infection
• Cerebral or B cell non-Hodgkin lymphoma
• Progressive multifocal leukoencephalopathy
• HIV-associated cardiomyopathy or nephropathy
Approach to Clinical Diagnosis

• A rational approach requires high index of suspicion with

knowledge in skilled diagnosis and management of HIV infection
in children

• Paediatric HIV presents with conditions that are also found in

HIV- children
• These conditions are broken down as:
• Common in both HIV+ & HIV- children
• Common in HIV+ but less common in HIV- children
• Specific to HIV infection

The Zambia Paediatric ART Training

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Curriculum
Clinical signs & conditions suggestive of HIV infection in a child

Common in both HIV+ and HIV- children

• Otitis media - persistent or recurrent

• Diarrhea – persistent or recurrent
• Severe pneumonia
• Tuberculosis
• Failure to thrive
• Bronchiectasis
• Marasmus
The Zambia Paediatric ART Training
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Curriculum
Clinical signs & conditions suggestive of HIV infection in a child
(cont’d)

Common in HIV, uncommon in HIV uninfected child

• Recurrent severe bacterial infections

• Persistent or recurrent oral thrush
• Parotid enlargement
• Generalized lymphadenopathy
• Hepatosplenomegaly (non-malaria areas)
• Persistent or recurrent fever
• Neurological dysfunction e.g. encephalopathy
• Persistent generalized dermatitis
The Zambia Paediatric ART Training
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Curriculum
Clinical signs & conditions suggestive of HIV infection in a child (cont’d)

Very specific for HIV infection:

• Recurrent invasive bacterial infection, excluding pneumonia (e.g.

empyema, pyomyositis etc)

• Esophageal candidiasis

• Herpes zoster (multidermatomal)

• Invasive salmonella infection

• Pneumocystis jirovecii (formerly carinii) pneumonia

The Zambia Paediatric ART Training
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Curriculum
Clinical signs & conditions suggestive of HIV infection in a child (cont’d)

Very specific for HIV infection:

• Extra pulmonary cryptococcosis

• Lymphoma

• Kaposi’s sarcoma

• Lymphocytic Interstitial Pneumonitis (LIP)

The Zambia Paediatric ART Training

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Curriculum
Ten point package of comprehensive care for HIV-exposed and infected children
QUESTIONS
Reference
• The Zambia Comprehensive Paediatric HIV/AIDS care Training
Curriculum
• ANECCA Textbook of Paediatric HIV 2017
THE END