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