Paediatric HIV

 Case
 Definition
 Incidence
 Aetiology
 Pathophysiology
Objectives  Clinical Presentation
 Differential Diagnosis
 Workup
 Treatment
 Complications
 A 13 year old male student presented to the A&E with a history of cough for 3 weeks,
lethargy, tiredness intermittently, fevers, weight loss and chills.

 His past medical history was unremarkable and there was not further information on
systematic enquiry.

 He had been seen at the regional polyclinic on 2 occasions in 3 weeks, and treated with
Paracetamol, and Histal DM , Amoxil for 1 week and two varieties of cough syrup. His
cough did not vary from day to night.

 His mother steed that the cough had worsened and that he was producing phlegm which
varied in colour from yellow to green for the past week.
Case
 His family history revealed that he is the only product of his unmarried parents' union. He
attend s the St George secondary school, is in 2nd form, and comes near last in class-with
20% average.

 The student was used to staying at a friend of the mother's who lived in the
neighbourhood on afternoons, during the school term, from 3pm to 6 pm until his mother
came home from work.
Examination revealed: His weight and height were on the 50th gentile. He has
clear cognitive deficits.

He was a febrile child (T-38 degrees C) with a normal blood pressure and oxygen
saturation of 85% consistently. He is RR was 45/ min and there were crepitations
scattered over the chest with vesicular breath sounds.
There was significant bilateral enlargement of inguinal lymph nodes 3 cm in
diameter, and 1cm axillary nodes.

Other systems were clinically normal. Genitalia were at Tanner stage 3.

Investigations including blood tests and radiological tests were done after
admission.

His ABG and C-xray wee abnormal.

He was treated with iIV amoxicillin for 1 week and then Azithromycin, however
her remained hypoxic and symptomatic of cough.

Other investigations were sent to the Lab.

 HIV – Human • A chronic RNA virus
Immunodeficiency
Virus infection in the host

Definition
• Presence of opportunistic or
AIDS – Acquired persistent infection or CD4+
Immunodeficiency
Syndrome lymphocyte count < 200 in
persons > 12 years of age
Definition

 A patient is HIV positive when both the ELISA and Western blot tests are positive
 A positive ELISA but negative Western blot = NO infection
 Infants born HIV-infected mothers have positive ELISA and Western blot due to
passive transfer of maternal antibodies
 This does not confirm infection
 Viral-specific testing must be performed
INCIDENCE

 In 2015: 150,000 children <15 years old were newly infected with HIV, bringing the
total number of children worldwide living with HIV or AIDS to 1.8 million
 Approx. 2/3 reside in Sub-Saharan Africa

 In Developed Countries: CDC estimates that the no. of infants born to HIV infected
mothers has decreased to 86 in 2015 (1650 in 1991)
 Developing Countries: in eastern and southern Africa, mother to infant
transmission declined from 18% in 2010 to 6% in 2015
2000
After start of the Prevention of mother to child transmission
(PMTCT) program
• ~ 80% decline in vertical transmission from 27.1% to 5.5% with long course AZT
monotherapy
• 8% transmission rate with NVP regimen

Between 2006-2012: HIV perinatal

transmission rates were < 1%

2006–2012

INCIDENCE (BARBADOS)
Aetiology

 HIV-1 and HIV-2

 Members of the Retroviridae family which belong to the Lentivirus genus
 HIV-1 genome contains 2 copies of single-stranded RNA
 Produces a reverse transcriptase -> viral RNA to act as a template for DNA
transcription and integration into the host genome

 HIV-1 causes 99% of all human cases

 HIV-2, less virulent, causes 1-9% of cases in parts of Africa
 Horizontal transmission

• Sexual contact
• Percutaneous contact
• Mucous membrane exposure to contaminated
Modes of blood products
Transmission
Vertical transmission

• Transplacentally in utero
• During birth
• During breastfeeding
TRANSMISSION

 Majority (90%) infected children acquire the infection through Mother-to-child

transmission (MTCT).
 This occurs during pregnancy, delivery and breastfeeding.

 Blood transfusions, blood products and organ/tissue transplants

 Contaminated needles
 Sexual intercourse/Abuse
HIV
STRUCTURE
PATHOPHYSIOLOGY
 CELLS SUSCEPTIBLE TO HIV INFECTION
SYSTEM CELL
Hematopoietic •T-cells
•Macrophages/monocytes
•Dendritic cells
•Fetal thymocytes and thymic epithelium
•B-cells
•NK Cells
•Megakaryocytic cells
•Stem cells

Central Nervous •Microglia

•Capillary endothelial cells
•Astrocytes
•Oligodendrocytes

Large Intestine •Columnar Epithelium

Other •Kupfer cells
•Synovial cells
•Placental trophoblastic cells
 A mild-to-moderate viremia as a result of
acute infection which rapidly increases
the viral load.
Viral loads decrease slowly in vertically
IMMUNE
infected children and may not reach
RESPONSE baseline levels until age 4-5 years.
Reduction in cytokine production,
proliferation, and cytotoxicity.
 The reduction in cell-mediated immunity and
secondary B-cell dysfunction result in the
immunocompromised state and in the proliferation of
opportunistic infections and malignancies.

IMMUNE
RESPONSE CD95/Fas receptor/ligand system Abnormalities:

• A low CD95+ T-cell count is found in asymptomatic patients who are

HIV positive.
• Increase in CD95+ T cells occurs as the immune status deteriorates.
 Cytopenias:

• Anaemia
• Neutropenia
• Thrombocytopenia
HAEMATOLOGICAL
EFFECTS
Thrombotic Thrombocytopenic Purpura

Coagulopathies and Coagulation Disorders

 HIV exhibits tropism for the CNS,
especially the microglia.

Approximately 10% of children

NEUROLOGICAL with AIDS have:
EFFECTS
• Progressive encephalopathy
• Progressive white matter degeneration
and brain atrophy may develop.
• Neurologic symptoms develop along with
developmental delay.
CLASSIFICATION
 CDC CLASSIFICATION
Age on Date of CD4 T + Lymphocyte Test

<1 year 1-5 years >6 years

Stage Cells/uL % Cells/uL % Cells/uL %

1 ≥1500 ≥34 ≥1000 ≥30 ≥500 ≥26

2 750-1499 26-33 500-999 22-29 200-499 14-25

3 <750 <26 <500 <22 <200 <14

 Clinical Stage 1
WHO
CLINICAL Asymptomatic
STAGING OF
HIV/AIDS FOR
CHILDREN
Persistent generalized
lymphadenopathy
Clinical Stage 2
Unexplained persistent hepatosplenomegaly
Papular pruritc eruptions
Fungal nail infection
Angular cheilitis
Lineal gingival erythema
Extensive wart virus infection
Extensive molluscum contagiosum
Recurrent oral ulcerations
Clinical Stage 3
Unexplained moderate malnutrition or wasting not adequately responding to standard therapy
Unexplained persistent diarrhea (≥14 days)
Unexplained persistent fever (>37.5 for >1 month)
Oral hairy leukoplakia
Acute necrotizing ulcerative gingivitis or periodontis
Lymph node tuberculosis
Pulmonary tuberculosis
Severe recurrent bacterial pneumonia
Clinical Stage 4
Unexplained severe wasting, stunting or severe malnutrition not responding to standard therapy
Pneumocystis pneumonia
Recurrent severe bacterial infections (such as empyema, pyomysitis, bone or joint infection)
Chronic herpes simplex infection
Esophageal candidiasis
Extrapulmonary tuberculosis
Kaposi sarcoma
CMV infection
The clinical manifestations of HIV infection in infants and children are varied and
often nonspecific.
An early sign may be lymphadenopathy frequently in association with
hepatosplenomegaly.
Growth failure, failure to thrive, or wasting

Developmental delay

CLINICAL MANIFESTATIONS
Selected AIDS-defining conditions:
Pneumocystis jirovecii pneumonia (PCP)
Recurrent bacterial infections
Wasting syndrome
Esophageal candidiasis
HIV encephalopathy
Cytomegalovirus pneumonia, colitis, encephalitis, or retinitis

CLINICAL MANIFESTATIONS
 Accounts for approximately 1/2 of all AIDS-defining
conditions diagnosed during the first year of life.

Median age of diagnosis – 5months

PNEUMOCYSTIS
JIROVECII PNEUMONIA
(PCP) Symptoms: Should be suspected in patients with
low-grade fever, tachypnea, non-productive cough,
and progressive shortness of breath.

Examination: lung auscultation may be normal even

in the presence hypoxemia; rales and rhonchi may
not become apparent until late in the clinical course.
 RTIs

Sinusitis

Bronchitis
RECURRENT
BACTERIAL Otitis media
INFECTIONS
Pharyngitis

Pseudomonas is associated with late-stage disease

and severe immunosuppression
 One of the following criteria must be met:

Persistent weight loss >10% of baseline.

WASTING
SYNDROME Downward crossing of two or more major
percentile lines on the pediatric weight-for-age
chart (eg, 95th, 75th, 50th, 25th, 5th)
<5th percentile on WFH chart on 2 consecutive
measurements 30 or more days apart, plus chronic
diarrhea or documented fever
 Risk factors:

Prior oral candidiasis,

ESOPHAGEAL Low CD4 count

CANDIDIASIS
Receipt of antibiotics

Symptoms: odynophagia, retrosternal pain, fever,

nausea and/or vomiting, drooling or dehydration and
hoarseness or GI bleeding.
 It’s is defined by one or more of the
following:
• Failure to attain developmental milestones, loss
of milestones, or loss of cognitive ability.
HIV • Impaired brain growth or acquired microcephaly.
ENCEPHALOPATHY • Acquired symmetric motor deficits manifested
by ≥2 of the following: paresis, pathologic
reflexes, ataxia, or gait disturbances

Can be Static or Progressive

CYTOMEGALOVIRUS DISEASE
- Transmission:
o MTCT
o Direct person-to-person contact with virus-containing secretions.
- An infectious mononucleosis-like syndrome with prolonged fever and
mild hepatitis can occur.
- CMV can present with fever, pneumonia, colitis, encephalitis, or
retinitis.
- Early CMV infection may accelerate HIV disease progression in
infants
  Constitutional Growth Delay
 Lymphadenopathy
 Malnutrition
 Nutritional Considerations in Failure to Thrive
DIFFERENTIAL  Paediatric Autoimmune and Chronic Benign
Neutropenia
DIAGNOSIS  Paediatric Chronic Anaemia
 Malabsorption Syndromes
 Severe Combined Immunodificiency
 Transient Hypogammaglobulinemia of
Infancy
 HIV detection is the first step in the
laboratory workup.

Detection of antibody to HIV is the usual first

step in diagnosing HIV infection.
WORKUP • HIV DNA PCR
• Viral Cultures
• ELISA
• Western Blot or Immunofluorescence Assay
• “Rapid” HIV test
• Blood count and viral load
HIV DNA PCR is used to detect HIV-1 provirus in mononuclear cells by
using oligonucleotides directed at highly conserved regions of the viral
genome.

ELISA for HIV antibody, followed by a confirmatory Western blot,

should be used to diagnose HIV infection in older children and adults.

Rapid HIV tests (sensitivity is as high as 100%), but they must be

followed with confirmatory Western blotting or immunofluorescence
antibody testing.
 The FDA has approved the APTIMA HIV-1 RNA Qualitative
Assay (Gen-Probe Incorporated, San Diego, CA).
 Enables certainty whether one is infected within a few days
rather than up to 6 months.
 The APTIMA assay is intended to detect only HIV-1 and not HIV-
2.
Viral Load testing
• Reverse-transcription PCR (RT-PCR) and nucleic acid
sequence—based amplification (NASBA) of plasma RNA
• Branched-chain DNA (bDNA) method.

Viral resistance testing

Studies
• Complete Blood Count
• Renal Function Test
• Liver Function Test
• Quantitative immunoglobulin levels should be followed up
periodically.
 Renal Imaging (US and CT Scan) in
Patients with HIV nephropathy.
 Diagnosis of Lymphoid
Interstitial Pneumonitis
What are the
radiological findings?
What’s the diagnosis?
How is it diagnosed?
Management
  Components of special care for these
infants include:
1. Antiretroviral prophylaxis
2. HIV diagnostic testing
Management 3. Evaluation for the need for PJP
of HIV-Exposed prophylaxis
Infants 4. Routine immunizations
5. Monitoring for manifestations of HIV
infection
6. Reinforcing education and counseling
for the mother and family
Neonatal ARV Prophylaxis

 All HIV-exposed infants should receive Zidovudine prophylaxis

 Started at birth ( preferably within 6 – 12 hours of delivery)
 Usual dose: GA >35 weeks: 4mg/kg po bd for 6 weeks

 High risk newborn, born to mothers who didn’t not receive ARV during pregnancy:
 Nevirapine should be given as 3 oral doses within 48 hour of birth

 Adverse effects:
 Zidovudine: anemia and neutropenia (most common)
HIV Virologic Testing Schedule

 HIV DNA PCR or HIV RNA assays

 within the first 14 to 21 days of life
 At age 1 to 2 months
 At age 4 to 6 months
PJP Prophylaxis

 All infants regardless of CD4 cell count or percentage should be prescribed PJP
prophylaxis at age 6 weeks
 Dose: 2.5-5 mg/kg TMP-SXM bd 3 days a week
 Standard childhood immunizations are
recommended, including influenza in CD4
counts are not profoundly low

Varicella vaccine shown to be safe in those with

Immunizations normal CD4 cell counts

Live viral vaccines should never be administered

to children with low CD4 cell counts
Monitoring

 Routine visits important for detecting:

 Faltering growth
 Abnormal neurodevelopment
 presence of opportunistic infections

 Provides opportunities to asses social support needs for mothers and families,
review results and reinforce safe feeding recommendations
 Management of HIV
Infection in Infants,
Children and Adolescents
Baseline Evaluation

 Mother’s Medical history

 Child’s Medical History
 Family history
 Social History
 Full physical examination and developmental evaluation
 In Adolescents: sexual history, substance use history, sexual maturity staging
 CD4 percentage and absolute cell counts
Viral load
HIV Genotype – access for baseline drug resistance

Initial Lab FBC with differential

Tests LFTs
U&Es
Lipid Profile
Urinalysis
 Goals: maximize the quality and longevity of life
through suppression of viral replication,
preservation or restoration of immunologic
function and prevention of or improvement in
clinical disease status
Goals and
Principles of
ART
Additional prevention goals: prevention of mother
to child transmission and reduction in sexual
transmission for HIV-infected youth
When to Start ART

 The decision requires balancing of health benefits of treatment with potential

adverse effects as well as patients readiness to take daily medications
 Recommendations for children and adolescents is based on their clinical stage,
level of CD4-defined immunodeficiency and to less extent, viral load.
 Non-nucleoside
reverse transcriptase
inhibitors (NNRTIs)

2 Nucleoside (or
nucleotide) reverse
Protease inhibitors
transcriptase inhibitors
(NRTIs) +

Integrase inhibitors

ART Regimens
Obstacles with Treatment

 ART efficacy depends on high levels of adherence to the regimen

 Frequent missed doses leads to drug resistance

 Planning treatment with the patient and family strengthens the therapeutic
relationship and promotes successful adherence and HIV control
 Patients generally achieve undetectable viral load within 6 months
 Failure to achieve within this time frame strongly suggest suboptimal adherence
rather viral resistance
  Once controlled on a stable regimen,
most patients are seen every 3 to 4
months for routine monitoring of:
 viral load
Monitoring  CD4 cell response
 clinical status
 evaluation for potential adverse or toxic
medication effects
 PJP prophylaxis with TMP-SXM

• All HIV-infected infants, children and adolescents with

CD4 values in the severe immune suppression
category
Prophylaxis
Mycobacterium avium complex
and
Immunizations • Primary prevention of MAC with azithromycin or
clarithromycin recommended at lower CD4 values:
• > 6 years: CD4 < 50 microL
• 2-6 years: < 75 microL
• 1-2 years: <500 microL
• <1 year: < 750 microL
Complications
ARV Drug Major Toxicity High Risk Situations
Stavudine - d4T Lipodystrophy CD4 count < 200 cells/mm
Neuropathy BMI >25 ( body weight >75 kg)
Lactic Acidosis Concomitant use with isoniazid or Didanosine
Zidovudine - AZT Anemia CD4 count < 200 cells/mm
Neutropenia BMI <18.5 ( body weight <50kg)
Anemia at baseline
Tenofovir - TDF Renal dysfunction Underlying renal disease
BMI <18.5
DM, HTN
Concomitant use of a bPI or nephrotoxic drugs
Efavirenz - EFV Psychiatric illness Depression or psychiatric disease (previously or at baseline)

Seizure (NB EFV may reduce concentrations of some

anticonvulsants)
Nevirapine - NVP Heptotoxicity HBV and HCV co infection

Rash Women pre-ART CD4 >250 cells/mm

Men pre-ART CD4 >400 cells/mm
Abacavir - ABC Hypersensitivity Race ( Caucasian > black)
(NB ABC may cause severe hypersensitivity rxns usually
within first 4-6 weeks of therapy which may be fatal)
Counseling and Support

 These should include:

1. Coping with the diagnosis and prognosis
2. Disclosure of HIV infection status
3. Adherence to care and treatment
4. School and sports participation
5. Transition to adult health care
References

 Siberry, G. K. (2014). Preventing and Managing HIV Infection in Infants, Children,

and Adolescents in the United States. Pediatrics in Review, 35(7), 268-286.
doi:10.1542/pir.35-7-268
 https://pedclerk.bsd.uchicago.edu/sites/pedclerk.uchicago.edu/files/uploads/PiRH
IVinfection.pdf
 Marcdante, K. J., & Kliegman, R. (2019). Nelson essentials of pediatrics.
Philadelphia, PA: Elsevier.
 HIV/STI programme, Ministry of Health, Barbados (2014). Barbados HIV
Management Guidelines 2014