Clinical presentation and
classification of HIV in children.
Gareth Tudor-Williams
St. Mary’s Hospital
&
Imperial College
London
Tr@in4PedHIV2009
How children present with HIV
How children are classified with HIV
How would you classify this
child?
• 8 months old
• Oral candidiasis
• Failure to thrive: z score
for weight is -2.1
HIV classification systems:
Only relevant for children whose HIV
infection is already confirmed
Not designed for diagnostic purposes
Ideally allocate prognostic
significance to presenting
symptoms/signs
How may infants present?
Can we detect primary
infection?
•
•
•
•
Rouet et al, DITRAME study, Abidjan
AIDS 2002; 16: 2303-9
Case control study
Mononucleosis-like illness plus
lymphadenopathy = 98% specificity
• Sensitivity = 27%, so PPV 82% if MTCT
rate high and less than 70% if MTCT low
Submandibular abscess
Lymph node enlargement ++
Severe FTT: 4.5kg at 12 mo
Dr. Israel Kalyesubula, Kampala
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Left Eye
Neuro-imaging of HIV
Encephalopathy
Basal ganglia calcification
White matter changes
Atrophy
Vasculopathy / Strokes
Presentation in older children
• May have mild symptoms during
childhood that HCW’s have failed to
recognise as indicative of HIV infection
• May present for first time in 2nd decade
of life
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Severe Molluscum
contagiosum
Why was a new classification
system needed?
WHO Clinical Staging System 1994
• Stage 1:
– Asymptomatic
– Generalized lymphadenopathy
• Stage 2:
– Unexplained chronic diarrhea
– Severe persistent or recurrent candidiasis
beyond the neonatal period
– Persistent fever
– Recurrent severe bacterial infections
– Weight loss or failure to thrive
WHO Staging System (con’t)
• Stage 3:
–
–
–
–
–
AIDS-defining opportunistic infection
Severe failure to thrive
Progressive encephalopathy
Malignancy
Recurrent septicemia or meningitis
Classification of HIV Disease
in Children, CDC 1994
• Clinical categories:
–
–
–
–
N: no symptoms
A: mild symptoms
B: moderate
C: severe symptoms
• Immunological
categories:
– 1: no impairment
– 2: intermediate
– 3: severe
Survival curves for European
children pre-HAART
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Clinical Classification: WHO or
Centers for Disease Control?
• Limitations to each system
– WHO
• Doesn’t capture many disease manifestations
• Doesn’t include measures of immunologic status
– CDC
• Often requires advanced diagnostic technology
• Doesn’t include more common manifestations seen in low
resource settings
• Neither system harmonised to Adult
classification
• One system should be used consistently
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WHO case definitions of HIV for surveillance and revised
clinical staging and immunological classification of HIVrelated disease in adults and children, 2007
http://www.who.int/hiv/pub/guidelines
WHO Revised Staging & Classification
Clinical classification
Stage 1
Stage 2
Stage 3
Stage 4
No symptoms
Mild
Advanced
Severe
+
Immunological classification
Not
significant
Mild
Advanced
Severe
Clinical classification on treatment
T1
T2
T3
T4
Survival by WHO stage CHAP cohort (n=540) Zambia
1.00
Proportion surviving
WHO stage 1/2, HR=1.00
0.75
WHO stage 3, HR=6.30
WHO stage 4 (weight only), HR=13.7
0.50
WHO stage 4 (with clinical malnutrition), HR=26.8
0.25
0.00
0
0.5
1
1.5
2
Years from randomisation
Walker AS et al. JAIDS 2006
WHO Revised Staging & Classification
Clinical classification
Stage 1
Stage 2
No symptoms Mild
Stage 3
Stage 4
Advanced
Severe
+
Immunological classification
Not
significant
Mild
Advanced
Severe
Clinical classification on treatment
T1
T2
T3
T4
Immunological staging
12-month mortality risk at selected thresholds for
CD4%, CD4 count and TLC, by age
30
CD4%<25 (<1yr), <20% (1 to <3 yrs), <15% (3 to <5 yrs), <15% (≥ 5 yrs)
CD4<1500 (<1yr), <750 (1 to <3 yrs), <350 (3 to <5 yrs), <200 (≥ 5 yrs)
P ro b a b ility o f d e a th (% )
25
TLC<4000 (<1yr), <3000 (1 to <3 yrs), <2500 (3 to <5 yrs), <2000 (≥ 5 yrs)
20
15
10
5
0
0
1
2
3
4
5
Age (years)
6
7
8
9
10
Immunological classification- all ages
Age related CD4
(%CD4+ or absolute count)
HIV associated
immunodeficiency
<11m
(%)
12-35m
(%)
36-59m
(%)
>5yr
(count/%
)
Not significant
> 35
>30
>25
<500
Mild
30-35
25-30
20-25
350-499
Advanced
25-29
20-24
15-19
201-349
Severe
<25
<20
<15
<200
CD4 Criteria for severe immunodeficiency
Age specific recommendation to initiate ART
[A-I]
Immunology
marker
< 11 mo
12-35 mo
36-59 mo
> 5 yrs
% CD4 +
<25
< 20
<15
<15
CD4
<1500
<750
<350
<200
mm3
count/cells
Rapid CD4 decline in infected infants
85% reach criteria to start HAART by 6
months
% above threshold
100
<20%
<25%
<30%
75
50
25
0
0
90
180
Days
270
360
Mphatswe et al, AIDS, 2007
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Members of the technical reference group on
pediatric HIV care and treatment
E. Abrams
G. Anabwani
C. Barker
F. Bwakura-Dangarembizi
D. Burger
E. Capparelli
D. Clarke
M. Cotton
F . Dabis
D. Dunn
B. Eley
J. Ellis
S. Essajee
T. Finkbeiner
F. Garcia
C.Giaquinto
D. Gibb
P. Humblet
A. Kaborè
A. Kekitiinwa
M. Kline
S. Lee
R. Lodha
C. Lwo
T. Meyers
M. Mirochnick
L. Mofenson
P. Msellati
J. Mukherjee
V. Mulenga
R Nduati
T. Nunn
M. Pate
J. Pinto
T. Puthanakit
E. Rivandeira
W. Schimana
P. Weidle
WHO Coordination:
S. Crowley
C. Gilks