Paediatric HIV MSD 2010
Overview
Epidemiology Paediatric disease progression Diagnosing HIV in children Clinical Staging (WHO) Common Signs and Symptoms
Western & Central Europe
13001300[<1000 – 1800][<1000 – 1800]
Middle East & North Africa26 00026 000
[18 000 – 34 000][18 000 – 34 000]Sub-Saharan Africa
1.8 million1.8 million[1.7 – 2.0 million][1.7 – 2.0 million]
Eastern Europe & Central Asia
12 000 12 000 [9100 – 15 000][9100 – 15 000]
South & South-East Asia
140 000140 000[[110 000 – 180 000110 000 – 180 000]]Oceania
11001100[1200][1200]
North America4400
[2600 – 7300]
Latin America44 00044 000
[37 000 – 58 000][37 000 – 58 000]
East Asia78007800
[5300 – 11 000][5300 – 11 000]Caribbean
11 000[9400 – 12 000]
Children (<15 years) estimated to be living with HIV, 2007
Total: 2.0 million (1.9 – 2.3 million)
Paediatric HIV/AIDS
More than 95% of HIV-infected children in Africa acquire HIV through MTCT
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
Plasma HIV RNA levels in Adults
1
100
10000
1000000
1 2 3 4 years 1 2 3
Months/Years
Vir
al lo
ad n
o.c
op
ies/
mL
(lo
g)
Viral load in children
Plasma HIV RNA levels in Infants
110
1001000
10000100000
1000000
1 2 years 2 2.5 3Months/Years
Vir
al lo
ad n
o. o
f co
pie
s/m
L (l
og
)
Disease Progression in Children
age < 2 years
age 3-10 years
•50% of all perinatally infected children will die before 2 years of age – “rapid progressors”
•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
Antibody tests (lab Elisa, rapid tests) can be reliably used in children > 18 months old
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%
CD4 count - higher in infancy than adulthood and variable
CD4 percentage remains constant
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+ %
1. No Immunosuppression
> 1500 > 25 >1 000 > 25 > 500 > 25
2. Moderate Immuno-suppression
750–1499 15–24 500–999 15–24 200-499 15 –24
3. SevereImmuno-suppression
< 750 < 15 < 500 < 15 < 200 < 15
Revised WHO Clinical Staging of HIV/AIDS for Infants and Children
‘HIV-infected’ ‘AIDS’
Stage 1Asymptomatic
Stage 2Mild disease
Stage 3Advanced
Stage 4Severe
WHO Clinical Stage 1
Asymptomatic Persistent generalized lymphadenopathy
(PGL)
Lymphadenopathy
Significant lymph node enlargement is more than 0,5cm in size, at more than 2 sites (bilateral =1 site)
WHO Clinical Stage 2 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
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
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
CTX can reduce mortality by 43% in children (Chintu et
al)
Activity against PCP, invasive bacterial infections ( respiratory and diarhoeal pathogens), toxoplasmosis and malaria
Side effects are rare 3.5 million children in Sub-Saharan Africa need CTX
prophylaxis (WHO) If early diagnosis is implemented can ↓ to 1.9 million
CTX ProphylaxisWhich children should get it?
All HIV-exposed infants from 6 weeks of age
All HIV-infected children not on ART
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
• Gastrointestinal conditions
• Skin and Mucosal conditions
• Nutritional conditions
• CNS
LRTI
Common organisms still most frequent Out-patient or in-patient ?
• Out-patient • Amoxil (7-10 days)
• Inpatient • IV Ampicillin (+ Gentamycin) or Cefuroxime
• Oxygen, fluids, monitoring (7-10 days)
• CXR, Bloods, PPD +/- AAFB (GW,Sputim)
LRTIs
LRTIs
Community Acquired Pneumonia• Bacterial
• Viral
Differential Diagnosis Pulmonary TB PCP LIP
Pneumocystis Jiroveci Pneumonia (PCP)
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)
• 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” 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
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
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)
Age usually greater than 2 years
Suggestive CXR findings:• bilateral reticulonodular infiltrates • mediastinal lymphadenopathy• indistinguishable from miliary TB
Child with slowly progressive hypoxia, tachypnoea and exertion fatigue.
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
Oral and/or oesophageal candidiasis Gastroenteritis – acute, persistent, chronic
• Infectious – Enteric / Parenteric (eg UTI)
• Villous atrophy
• Enzyme deficiencies – lactase
• Drug related (Kaletra®)
Perianal fistulae Colitis – CMV Fistulae – RV fistulae
Dermatological conditions• Seborrhoiec dermatitis • Eczema• Scabies• Warts • Varicella-Zoster • Molluscum contagiosum• Tinea – (all)
Think Immunodeficiency if …..
any common condition shows the following charactersitics
ATYPICAL presentation INTRACTABLE to conventional
treatment SEVERE & EXTENSIVE RECURRENT
Shingles (Zoster)
Dermatitis
• 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)
• 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
• Failure to Thrive (FTT)
• Marasmus
• Kwashiorkor
CNS 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
Indicates advanced clinical disease (WHO IV) HAART indicated with good but variable result and
reversibility Diagnosis
• 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 OIs:
• Bacterial meningitis,
• TBM,
• Cryptococcus,
• CMV encephalitis
• Varicella reactivation
• Toxoplasmosis Vasculitides: well described, varied presentation Malignancy: lymphoma PML - JCV
HAARTOverview
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)
Recurrent hospitalisations (> 2 admissions per year) or prolonged hospitalisation (> 4 weeks) for HIV complications
WHO Stage III or IV
For relatively asymptomatic patients:• CD4 percentage <20% if < 18 months • CD4 percentage <15% if > 18 months.
Proposed New Start Criteria
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)
MandatoryAt least one identifiable caregiver who is able to
supervise child or administer medication
(Do not exclude orphans and the abandoned)
RecommendedDisclosure 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
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 >3 years (>10kg)
1st line stavudine (d4T)lamivudine(3TC)kaletra®
stavudine (d4T)lamivudine(3TC)efavirenz (stocrin)
2nd line zidovudine (AZT)didanosine (ddI)efavirenz (Stocrin)
zidovudine (AZT)didanosine(ddI)kaletra® (Stocrin)
ARV dosing
Body Surface Area (BSA)
Standardised weight tables (WHO) in DOH guidelines
Doses must be adjusted for weight as children grow
BSA (m2) = height (m) x weight (kg) 3600
Monitoring
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 effectsSome 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
Life threatening:• Lactic acidosis- all NRTI’s (d4T+ddI) no good way of
screening→clinical suspicion• Hypersensitivity (ABC)• Hepatitis (NVP)• SJS (NNRTI)• Pancreatitis• Cardiomyopathy
Other:• Lipodystrophy, lipid profile abn, diabetes (PI)• Peripheral neuropathy (NRTI)• Myopathy (NRTI)• Bone marrow suppression (AZT)
Lactic AcidosisInitial 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
Pathogenesis - improving immune system interacts with organisms that have colonised the body during the early stages of HIV infection.
Disease processes : Infectious Non-Infectious
Immune-reconstitution disease 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!!!