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Preliminary deliberations towards estimating the burden of HIV disease in children, in the light of need for ART Marie-Louise Newell, Kirsty Little, Madeleine.

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Presentation on theme: "Preliminary deliberations towards estimating the burden of HIV disease in children, in the light of need for ART Marie-Louise Newell, Kirsty Little, Madeleine."— Presentation transcript:

1 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)

2 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

3 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

4 Examples of number of infected and uninfected children SettingEst PopEst no births HIV %No PMTCT PMTCT West Africa 51,7 m1,894,5254-8 %28,98021,320 East Africa 140,0 m5,771,2214-16%194,287129,524 Sthrn Africa 83,2 m2,448,80220-40%222,715148,477 W Africa: Burkina Faso, Cote dIvoire, Ghana; E Africa: Kenya, Uganda, Rwanda, Ethiopia; Southern Africa: SA, Zimbabwe, Malawi, Zambia, Botswana

5 Examples 2 of number of infected and uninfected children SettingEst PopEst no births HIV %No PMTCT PMTCT Asia1,159 m26,540,4420.25- 3.5% 26,29917,109 Estrn Europe 194,8 m1,682,4961%3,3651,669 Asia: Cambodia, India, Thailand Eastern Europe: Ukraine, Moldova, Russian Fed

6 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

7 Number of infected children alive at selected ages – no PMTCT, with PMTCT Setting1 yr2 yr5 yr10 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

8 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%

9 Infected children alive at selected ages needing ARV on the basis of AIDS no PMTCT, with PMTCT SettingAIDS1 yrAIDS2 yrAIDS5 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

10 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%

11 Distribution of CD4% by age HIV Paediatric Prognostic Markers Collaborative Study, 2004, with thanks to Trinh Duong and Di Gibb

12 Distribution of TLC by age HIV Paediatric Prognostic Markers Collaborative Study, 2004, with thanks to Trinh Duong and Di Gibb

13 Children at selected ages eligible for ARV on the basis of CD4% - no PMTCT, with PMTCT Setting1 yr2 yr3 yr5 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

14 Children at selected ages eligible for ARV on the basis of TLC- no PMTCT, with PMTCT Setting1 yr2 yr3 yr5 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

15 Eligibility on the basis of AIDS, CD4% or TLC at age 2 years, no PMTCT

16 Eligibility on the basis of AIDS, CD4% or TLC at age 5 years, with PMTCT

17 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%

18 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

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20 Distribution of CD4 count by age HIV Paediatric Prognostic Markers Collaborative Study, 2004, with thanks to Trinh Duong and Di Gibb

21 Comparison eligibility AIDS, CD4%, TLC at ages 2 and 5 years; no PMTCT, with PMTCT SettingAt 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 572 286 611 305 152 189 213 218 110 135 67


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