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Paediatric HIV
MSD 2010
Overview
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Epidemiology
Paediatric disease progression
Diagnosing HIV in children
Clinical Staging (WHO)
Common Signs and Symptoms
Children (<15 years) estimated to be living with HIV,
2007
Western & Eastern Europe
Central Europe & Central Asia
1300
North America
4400
[2600 – 7300]
Caribbean
11 000
[<1000 – 1800]
12 000
[9100 – 15 000]
Middle East & North
Africa
[9400 – 12 000]
26 000
[18 000 – 34 000]
Sub-Saharan Africa
Latin America
44 000
[37 000 – 58 000]
1.8 million
[1.7 – 2.0 million]
East Asia
7800
[5300 – 11 000]
South & South-East
Asia
140 000
[110 000
– 180 000]
Oceania
1100
[1200]
Total: 2.0 million (1.9 – 2.3 million)
Paediatric HIV/AIDS
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More than 95% of HIV-infected children in Africa
acquire HIV through MTCT
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HIV infection in foetus and newborn occurs in the
setting of an immature immune system
Feeble immune responses to HIV
More rapid and extensive virus replication than in older hosts
More rapid disease progression
Viral load in adults
Viral load no.copies/mL (log)
Plasma HIV RNA levels in Adults
1000000
10000
100
1
1
2
3
4
years
Months/Years
1
2
3
Viral load in children
Viral load no. of
copies/mL (log)
Plasma HIV RNA levels in Infants
1000000
100000
10000
1000
100
10
1
1
2
years
2
Months/Years
2.5
3
Disease Progression in Children
•50% of all perinatally infected
children will die before 2 years of age
– “rapid progressors”
age < 2
years
age 3-10
years
•Half will die between 3 and 10 years
of age – “slow progressors”
•A child that presents early (< 1 year of
age) is more likely to die quickly
Laboratory diagnosis of HIV
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Antibody tests (lab Elisa, rapid tests) can
be reliably used in children > 18 months
old
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PCR testing is reliable from 6 weeks of
age, if the baby has not been breastfed
for the preceding 6 weeks
• On whole blood
• On Dry Blood Spots
Absolute CD4 Count vs. CD4%
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CD4 count - higher in infancy than
adulthood and variable
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CD4 percentage remains constant
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CD4 percentage correlates with disease
progression in children
CDC Immunological Classification
for human immunodeficiency virus infection
in children less than 13 years of age. MMWR 1994;43.
AGE OF CHILD
<12 MONTHS
1-5 YEARS
6-12 YEARS
IMMUNOLOGICAL
CATEGORY
CD4+/ul
CD4+ %
CD4+/ul
CD4+%
CD4+/ul
CD4+ %
> 1500
> 25
>1 000
> 25
> 500
> 25
750–1499
15–24
500–999
15–24
200-499
15 –24
< 750
< 15
< 500
< 15
< 200
< 15
1. No
Immunosuppression
2. Moderate
Immuno-suppression
3. Severe
Immuno-suppression
Revised WHO Clinical Staging of HIV/AIDS for
Infants and Children
Stage 1
Stage 2
Stage 3 Stage 4
Asymptomatic
Mild disease
Advanced
‘HIV-infected’
Severe
‘AIDS’
WHO Clinical Stage 1
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Asymptomatic
Persistent generalized lymphadenopathy
(PGL)
Lymphadenopathy
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Significant lymph
node enlargement
is more than
0,5cm in size, at
more than 2 sites
(bilateral =1 site)
WHO Clinical Stage 2
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Hepatosplenomegaly
Recurrent or chronic URTI
Papular pruritic eruptions
Seborrhoeic dermatitis
Extensive human papilloma virus infection
Extensive molluscum infection
Herpes zoster
Fungal nail infections
Recurrent oral ulcerations
Lineal Gingival Erythema (LGE)
Angular chelitis
Parotid enlargement
WHO Clinical Stage 3
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Unexplained moderate malnutrition
Unexplained persistent diarrhoea (14 days or more)
Unexplained persistent fever, for longer than 1month)
Oral candidiasis (outside neonatal period )
Pulmonary TB
Severe recurrent presumed bacterial pneumonia
Lymphoid interstitial pneumonitis (LIP)
Unexplained anaemia, neutropenia or thrombocytopenia for
more than 1 month
Chronic HIV associated lung disease
Oral hairy leukoplakia
Necrotising ulcerative gingivitis/periodontitis
WHO Clinical Stage 4
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Unexplained severe wasting
PCP
Recurrent severe presumed bacterial infections (excl.
pneumonia)
Chronic Herpes simplex infection
Extrapulmonary tuberculosis
Kaposi's sarcoma
Disseminated non-tuberculous mycobacteria infection
HIV encephalopathy
Disseminated endemic mycosis (extrapulmonary
histoplasmosis, coccidiomycosis, penicilliosis)
CNS toxoplasmosis (outside the neonatal period)
Cytomegalovirus (CMV) infection
• Extrapulmonary cryptococcosis including meningitis
• Chronic Cryptosporidiosis, Isosporiasis
Cotrimoxazole (CTX) prophylaxis
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CTX can reduce mortality by 43% in children (Chintu et
al)
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Activity against PCP, invasive bacterial infections (
respiratory and diarhoeal pathogens), toxoplasmosis
and malaria
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Side effects are rare
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3.5 million children in Sub-Saharan Africa need CTX
prophylaxis (WHO)
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If early diagnosis is implemented can ↓ to 1.9 million
CTX Prophylaxis
Which children should get it?
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All HIV-exposed infants from 6 weeks of age
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All HIV-infected children not on ART
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Stop if HIV infection excluded or child on ART
with evidence of immune reconstitution for 6
months
• CD4% > 20%
Common Presenting Signs &
Symptoms
•
Respiratory conditions
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Gastrointestinal conditions
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Skin and Mucosal conditions
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Nutritional conditions
•
CNS
LRTI
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LRTIs
Common organisms still most frequent
Out-patient or in-patient ?
Out-patient
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Amoxil (7-10 days)
Inpatient
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IV Ampicillin (+ Gentamycin) or Cefuroxime
Oxygen, fluids, monitoring (7-10 days)
CXR, Bloods, PPD +/- AAFB
(GW,Sputim)
LRTIs
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Community Acquired Pneumonia
• Bacterial
• Viral
Differential Diagnosis
Pulmonary TB
PCP
LIP
Pneumocystis Jiroveci Pneumonia
(PCP)
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Suspect a PCP infection if the child:
<12 months old
Has severe tachypnoea
• (> 50 breaths/minute in infants, >40 breaths/minute in
children)
Is dyspnoeic
Has few crackles relative to degree of dyspnoea and
decreased breath sound intensity on auscultation
Has cyanosis
Begin treating for PCP immediately on suspicion
(in addition to usual treatment of pneumonia), even if the
HIV status of the child is not yet known
Pneumocystis Jiroveci
Pneumonia (PCP)
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Requires admission
Maximal oxygen supplementation
NPO for first 24-48hrs / NGT feeds
Co-Trimoxazole 20mg/kg qid IVI/oral (3wks)
Prednisone 1-2mg/kg x 14 days
Adequate fluids, but do not overhydrate !
“BCGosis”
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BCG (Bacille Calmette Guerin)
Routine vaccine at birth
Given to ALL babies
BCGosis = BCGitis may be localized or
generalized (disseminated)
Occurs in both HIV infected and non –
infected children
May occur prior to HAART or as IRIS
BCG adenitis
Mycobacterium Avium Complex
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M. avium
M. intracellulare
M.paratuberculosis
Disseminated infection with MAC in pediatric
HIV infection rarely occurs in infancy
Frequency  with age and declining CD4
count,
Diagnosis
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Definitive diagnosis is accomplished by
isolation of the organism from the
BLOOD or from BIOPSY SPECIMENS from
normally sterile sites (e.g. bone marrow,
lymph node, or other tissues).
Multiple mycobacterial blood cultures over
time might be required to yield a positive
result.
Lymphoid Interstitial
Pneumonitis (LIP)
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Age usually greater than 2 years
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Suggestive CXR findings:
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bilateral reticulonodular infiltrates
mediastinal lymphadenopathy
indistinguishable from miliary TB
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Child with slowly progressive hypoxia, tachypnoea and
exertion fatigue.
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Child with clubbing and enlarged parotid glands
LIP
vs.
Miliary TB
Digital Clubbing
LIP Treatment
No treatment for asymptomatic LIP
Symptomatic LIP - i.e. oxygen sats < 92% or
developing signs of cor pulmonale
• Prednisone 2mg/kg x 4 weeks then taper dose.
• Need to exclude PTB and/or treat prior to steroid use
• Indication for HAART – to decrease need for steroid
Gastrointestinal
Conditions
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Oral and/or oesophageal candidiasis
Gastroenteritis – acute, persistent, chronic
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Infectious – Enteric / Parenteric (eg UTI)
Villous atrophy
Enzyme deficiencies – lactase
Drug related (Kaletra®)
Perianal fistulae
Colitis – CMV
Fistulae – RV fistulae
Dermatological
conditions
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Seborrhoiec dermatitis
Eczema
Scabies
Warts
Varicella-Zoster
Molluscum contagiosum
Tinea – (all)
Think
Immunodeficiency if …..
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any common condition shows the
following charactersitics
ATYPICAL presentation
INTRACTABLE to conventional
treatment
SEVERE & EXTENSIVE
RECURRENT
Shingles (Zoster)
Dermatitis
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Treat with Procutan (1% hydrocortisone) cream to face 12
hourly until improves
Use Aqueous cream as soap
On the body use betnovate 1 in 10 with aqueous cream
12 hourly until improves (usually for 7-14 days).
Seborrhoeic Dermatitis
Treat with Procutan
(1% hydrocortisone) or
betnovate 1 in 10 with
aqueous cream twice a day
until rash resolves
Molluscum Contagiosum
• HAART indicated
•Apply topical tincture of iodine BP to the core
of each lesion using an applicator
•At hospital: cryotherapy/surgical excision
Ringworm (Tinea Capitis)
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If mild, try Whitfield
ointment (6% benzoic
acid and 3 % salicylic
acid ) 2-3 times daily for
4-6 weeks
For nail and scalp
infections need
Griseofulvin 10mg/kg
daily for 8 weeks
Oral Candidiasis
Note – Oral candidiasis common condition in very young infants,
not necessarily associated with HIV
Nutritional conditions
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Failure to Thrive (FTT)
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Marasmus
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Kwashiorkor
CNS
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Direct effect of virus – HIV Encephalopathy
Indirect effect – secondary to illnesses and
therefore delayed development
Opportunistic infections
Neoplasia
Vasculitides
Immune reconsitution phenomena
Drug related phenomena
Unrelated to HIV in child e.g. birth related brain
injury, fetal alcohol syndrome, etc
HIV Encephalopathy
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Indicates advanced clinical disease (WHO IV)
HAART indicated with good but variable result and
reversibility
Diagnosis
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Take a good birth history
Slow achievement or loss of milestones or loss of intellectual ability
Acquired microcephaly
Acquired symmetrical motor deficits in an alert child - increased
tone, pathologic reflexes, ataxia, gait disturbances, paresis
CSF is normal or has non-specific findings
CT scan shows diffuse brain atrophy
Rule out CNS infections/conditions
CNS complications
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OIs:
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Bacterial meningitis,
TBM,
Cryptococcus,
CMV encephalitis
Varicella reactivation
Toxoplasmosis
Vasculitides: well described, varied presentation
Malignancy: lymphoma
PML - JCV
HAART
Overview
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When and how to start ART
Paediatric ART Regimens
Monitoring
Adverse effects
Immune Reconstitution
Drug interactions
Adherence
When do we start?
When to start?
(DOH Guidelines)
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Recurrent hospitalisations (> 2 admissions
per year) or prolonged hospitalisation (> 4
weeks) for HIV complications
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WHO Stage III or IV
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For relatively asymptomatic patients:
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CD4 percentage <20% if < 18 months
CD4 percentage <15% if > 18 months.
Proposed New Start Criteria
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ALL HIV-infected infants irrespective of
CD4 % or clinical stage
For children 1-5 yrs CD4 < 25%
For children > 5 yrs CD4 < 350 cells/ml
Psychosocial Criteria
(DOH Guidelines)
Mandatory
At least one identifiable caregiver who is able to
supervise child or administer medication
(Do not exclude orphans and the abandoned)
Recommended
Disclosure to another adult living in the same
house is encouraged so that there is someone
else who can assist with the child’s ART
Preparing a child for ART
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Establish a definitive HIV diagnosis and WHO stage
the patient
Screening CD4%
Exclude TB (treat if suspicious)
Treat intercurrent illnesses and opportunistic disease
first.
Identify responsible person to administer treatment.
Optimise caregiver and family health
• Counsel and educate about ART,
demonstrate
Regimens for Children
(DOH Guidelines)
Birth - 3years
1st line
stavudine (d4T)
lamivudine(3TC)
kaletra®
2nd line zidovudine (AZT)
didanosine (ddI)
efavirenz (Stocrin)
>3 years (>10kg)
stavudine (d4T)
lamivudine(3TC)
efavirenz (stocrin)
zidovudine (AZT)
didanosine(ddI)
kaletra® (Stocrin)
ARV dosing
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Body Surface Area (BSA)
BSA (m2) =
height (m) x weight (kg)
3600
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Standardised weight tables (WHO) in DOH
guidelines
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Doses must be adjusted for weight as children
grow
Monitoring
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Baseline CD4, Viral Load, (FBC), (ALT)
1-month visit, and 3-monthly clinical
exam
6-monthly CD4, Viral load unless
indicated otherwise
Toxicity depending on drug regimen
Side effects
Some toxicities are class-specific while others are drug-specific
NRTI’s: lactic acidosis, hepatic steatosis, pancreatitis, myopathy,
cardiomyopathy and peripheral neuropathy
NNRTI’s: Rash (SJS-nvp), Hepatitis (CNS-efavirenz)
PI’s: Insulin resistance, diabetes, hyperlipidemia, lipodystrophy,
increased bleeding episodes in haemophiliacs, hepatitis, and
bone disorders
Adverse events
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Life threatening:
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Lactic acidosis- all NRTI’s (d4T+ddI) no good way of
screening→clinical suspicion
Hypersensitivity (ABC)
Hepatitis (NVP)
SJS (NNRTI)
Pancreatitis
Cardiomyopathy
Other:
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Lipodystrophy, lipid profile abn, diabetes (PI)
Peripheral neuropathy (NRTI)
Myopathy (NRTI)
Bone marrow suppression (AZT)
Lactic Acidosis
Initial symptoms are variable, cases have occurred as soon
as 1 month and as late as 20 months after starting therapy,
Usually associated with combination DDI and D4T
Clinical prodromal syndrome:
 generalized fatigue, weakness
 gastrointestinal symptoms (nausea, vomiting, diarrhea,
abdominal pain, hepatomegaly, anorexia, and/or sudden
unexplained weight loss)
 respiratory symptoms (tachypnea and dyspnea)
 neurologic symptoms (including motor weakness)
Immune-reconstitution disease
Synonyms : ‘Immune Reconstitution Syndrome’
‘Immune Reconstitution Inflammatory Syndrome’
Paradoxical clinical deterioration after starting HAART
Presentation:
 Usually affects those with very low starting CD4 count
(often CD4 nadirs <100)
 IRD usually presents during the first 6 weeks after starting
HAART.
 Clinical presentations depend on the causative organism
and the organ-system that is colonised.
Immune-reconstitution disease
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Pathogenesis - improving immune
system interacts with organisms that
have colonised the body during the early
stages of HIV infection.
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Disease processes :
 Infectious
 Non-Infectious
Immune-reconstitution disease
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Infectious Diseases :
Mycobacterium tuberculosis (MTB),
Mycobacterium avium complex,
Mycobacterium leprae, Cryptococcus
neoformans, Aspergillus fumigatus, Aspergillus
terreus, Candida albicans, Pneumocystis
carini, CMV, JC virus, Human Herpes viruses,
Human Papilloma virus and hepatitis B and C
viruses.
6 weeks later!!!