Preliminary deliberations towards estimating the burden of HIV disease in children, in the light of need for ART
Marie-Louise Newell, Kirsty Little, Madeleine Bunders (Ghent-IAS Group on HIV infection in women and children)
Background
• Mother-to-child transmission of HIV accounts for nearly all HIV infection in children
• Although MTCT in the peripartum period can be prevented, the numbers of HIV infected children continues to increase
• HIV infection has been associated with an increase in child mortality seen in many areas of sub-Saharan Africa over the past decade
• However, there is a lack of data to inform estimates of the number of infected children, the number progressing to serious clinical disease and death and even less data on the number reaching immunological cut-offs for initiation of ARV
• The burden of HIV disease in children in terms of the need of care, in particular ARVs, is thus difficult to estimate
Estimating the number of children born to HIV infected
women• Population estimates and birth rates taken from
UNPOP website to estimate number of deliveries by country
• Antenatal HIV prevalences were based on UNAIDS published estimates, Asamoah-Odei 2004, with adjustments based on additional personal information and were used to calculate the numbers of infants born to HIV infected women
• In breastfeeding populations in the absence of interventions the rate of MTCT was assumed to be 30% and with PMTCT 20%
• In non-breastfeeding populations the assumed rates were 20% and 10% respectively
• This thus gives per country an estimated number of infected and uninfected infants
Examples of number of infected and uninfected
childrenSetting Est Pop Est no
birthsHIV % No
PMTCTPMTCT
West Africa
51,7 m 1,894,525 4-8 % 28,980 21,320
East Africa
140,0 m 5,771,221 4-16% 194,287 129,524
Sthrn Africa
83,2 m 2,448,802 20-40% 222,715 148,477
W Africa: Burkina Faso, Cote d’Ivoire, Ghana; E Africa: Kenya, Uganda, Rwanda, Ethiopia; Southern Africa: SA, Zimbabwe, Malawi, Zambia, Botswana
Examples 2 of number of infected and uninfected
children
Setting Est Pop Est no births
HIV % No PMTCT
PMTCT
Asia 1,159 m 26,540,442 0.25-3.5%
26,299 17,109
Estrn Europe
194,8 m 1,682,496 1% 3,365 1,669
Asia: Cambodia, India, ThailandEastern Europe: Ukraine, Moldova, Russian Fed
Estimated number of children alive at selected ages -
assumptions• There is a lack of data after age 2, but Spira provides
some information up to age 5 year. Thereafter annual mortality is assumed to be constant and at a rate of 10%
• Cumulative mortality rates (from Newell et al 2004, and adjusted Spira et al 1999): at age 1 year 35.2%, 2 yr 52.5%, 5 yr 75% and 10 yr 85%
• It is assumed that for infected children mortality rates in Eastern Europe and Asia are comparable with those estimated for Africa
Number of infected children alive at selected ages – no PMTCT, with PMTCT
Setting 1 yr 2 yr 5 yr 10 yr
West Africa
20,734
13,815
15,191
10,127
7,995
5,330
4,721
3,147
East Africa
125,897
83,932
92,266
61,524
48,572
32,381
28,681
19,121
Sthrn Africa
144,320
96,214
105,790
70,527
55,678
37,119
32,877
21,918
Asia 17,043
11,086
12,492
8,127
6,575
4,277
3,882
2,526
E Eur 2,180
1,090
1,598
799
841
420
497
248
Assumptions re the estimated number of children who need ARV on the basis of
clinical disease progression• 80% of infants diagnosed with AIDS in their first year of life will have
died before age 1 year• The remaining 20% will have the same probability of death as children
diagnosed with AIDS in year 2• Children diagnosed with AIDS after 1 year have a 30% probability of
dying within a year• All those diagnosed with AIDS and alive at given ages will require
treatment
• Cumulative probability of being diagnosed with AIDS by 1 yr: 0.17, by 2 yr 0.28 and by 5 yr 0.35 (from Spira)
• Estimated percentage of children diagnosed with AIDS by 1 year of age: 17%, between 1 and 2 years of age 15.4% and between 2 and 5 yr 18.4%
Infected children alive at selected ages needing ARV on the basis of AIDS no PMTCT, with PMTCT
Setting AIDS 1 yr AIDS 2 yr AIDS 5 yr
West Africa
5,436
3,624
1,087
725
3,197
2,132
2,999
2,001
2,239
1,492
1796
1,198
East Africa
33,030
22,019
6,606
4,404
19,428
12,952
18,224
12,149
13,601
9,065
10,915
7,277
Sthrn Africa
37,862
25,241
7,573
5,048
22,271
14,847
20,890
13,927
15,590
10,394
12,512
8,342
Asia 4,471
2,908
895
582
2,630
1,711
2,467
1,604
1,840
1,197
1,477
962
E Eur 572
286
114
58
337
168
316
158
235
118
189
95
Estimating the number of children eligible for ARV on the basis of CD4% or total
lymphocyte counts• Number of children in various CD4 or TLC
categories at given ages taken from Dunn et al – HIV Paediatric Prognostic Markers Collaborative Study paper in preparation – with additional information provided by Trinh Duong
• These data come from European and American cohort studies and trials, but there are no such data from Africa
• WHO below 18mths: TLC <2500 cells and CD4% < 20%; above 18 mths: < 1500 and < 15%
Distribution of CD4% by age
0
20
40
60
80
100
3m 6m 1 2 3 4 5 6 7 8 9 10
Age (years)
Perc
enta
ge o
f val
ues
<10 10- 15- 20-
HIV Paediatric Prognostic Markers Collaborative Study, 2004, with thanks to Trinh Duong and Di Gibb
Distribution of TLC by age
0
20
40
60
80
100
3m 6m 1 2 3 4 5 6 7 8 9 10Age (years)
Perc
enta
ge o
f val
ues
<1000 1000- 1500- 2000- 2500-
HIV Paediatric Prognostic Markers Collaborative Study, 2004, with thanks to Trinh Duong and Di Gibb
Children at selected ages eligible for ARV on the basis of CD4% - no PMTCT, with PMTCT
Setting 1 yr 2 yr 3 yr 5 yr
West Africa 6,397
4,263
5,802
3,868
3,197
2,127
2,079
1,386
East Africa 38,858
25,906
35,249
23,501
19,428
12,920
12,628
8,420
Sthrn Africa
44,323
29,696
40,410
26,940
22,271
14,810
14,476
9,651
Asia 5,259
3,421
4,772
3,104
2,630
1,707
1,710
1,113
E Eur 673
337
611
305
337
168
218
110
Children at selected ages eligible for ARV on the basis of TLC- no PMTCT, with PMTCT
Setting 1 yr 2 yr 3 yr 5 yr
West Africa 4,158
2,771
2,882
1,934
1,215
811
1,280
852
East Africa 25,258
16,837
17,626
11,749
7,383
4,921
7,772
5,181
Sthrn Africa
28,954
19,302
20,203
13,471
8,463
5,653
8,909
5,940
Asia 3,419
2,224
2,386
1,552
1,000
650
1,052
685
E Eur 437
218
305
152
128
65
135
67
Eligibility on the basis of AIDS, CD4% or TLC at age 2
years, no PMTCT
0
10000
20000
30000
40000
50000
W Africa E Africa S Africa Asia E Europe
TLCAIDSCD4%
Eligibility on the basis of AIDS, CD4% or TLC at age 5
years, with PMTCT
0
2000
4000
6000
8000
10000
W Africa E Africa S Africa Asia E Europe
TLCAIDSCD4%
Summary• More children would be eligible for treatment on the
basis of CD4% than because of AIDS, and the number of children requiring treatment using current cut-offs for TLC is always the lowest
• Dunn et al estimate that the number of deaths before reaching the immunological marker value triggering therapy is about 4-6% by age 6 yrs (based on a European-American population)
• They also estimate that the cumulative probability of observing a marker value triggering ARV before death increases from 12% (TLC) - 24% (CD4%) at first measurement to 50% (TLC) - 60% (CD4%) 6 years later
• In our preliminary model, of children alive at age 2 years 20% would be eligible for ARV on the basis of AIDS, 38% on CD4% and 19% on TLC; at age 5 yrs these percentages are: 22.5%, 26% and 16%
Conclusion• Estimated number of infected children in sub-Saharan
Africa (12 countries) ranges from 300,000 to 450,000 per year, of whom an estimated 75,000 to 112,500 will be alive at 5 years of age. Of these about one-quarter would need ARV on the basis of AIDS or CD4%
• Numbers in Asia and Eastern Europe are currently small, because the antenatal prevalence is low
• This preliminary model has many limitations, but could be made more complex, by for example allowing for differential mortality by age at acquisition of infection and immunological status, but the limiting factor remains the lack of data from Africa and other resource-limited settings, with the associated considerable uncertainty in the basic rates of antenatal seroprevalence, survival of infected children, clinical and immunological disease progression and predictive value of immunological or clinical manifestations
Distribution of CD4 count by age
0
20
40
60
80
100
3m 6m 1 2 3 4 5 6 7 8 9 10
Age (years)
Perc
enta
ge o
f val
ues
<200 200- 500- 1000- 1500-
HIV Paediatric Prognostic Markers Collaborative Study, 2004, with thanks to Trinh Duong and Di Gibb
Comparison eligibility AIDS, CD4%, TLC at ages 2 and 5 years; no PMTCT, with PMTCT
Setting At 2
AIDS
At 2
CD4%
At 2
TLC
At 5
AIDS
At 5
CD4%
At 5
TLC
West Africa
5,436
3,624
5,802
3,868
2,882
1,934
1,796
1,198
2,079
1,386
1,280
852
East Africa
33,030
22,019
35,249
23,501
17,626
11,749
10,915
7,277
12,628
8,420
7,772
5,181
Sthrn Africa
37,862
25,241
40,410
26,940
20,203
13,471
12,512
8,342
14,456
9,651
8,909
5,940
Asia 4,471
2,908
4,772
3,104
2,386
1,552
1,477
962
1,710
1,113
1,052
685
E Eur 572
286
611
305
305
152
189
213
218
110
135
67