1. Current Status of HIV Surveillance in Children: Gaps and Future Directions Mary Lou Lindegren, MD Global AIDS Program Centers for Disease Control and Prevention 5 th IAS Conference 2009

2. Outline Current data needs, sources, and estimates –Incidence of HIV among children born to HIV- positive mothers –HIV free survival –HIV prevalence among children –Morbidity –Mortality Future approaches to expanding pediatric HIV surveillance

3. Magnitude of the Problem ~ 2 million children (<15 years) living with HIV; 90% of them live in sub-Saharan Africa¹ ~ 2,086,000 million HIV+ women give birth globally (2005, UNICEF) An estimated 370,000 children < 15 became infected with HIV in 2007 ¹From the 2008 UNAIDS report on the Global Epidemic

4. Births to HIV infected mothers Estimates-UNAIDS ANC surveillance L&D surveillance PMTCT program HIV case reporting Immunization surveys Prevalence and morbidity Population-based surveys with HIV testing, younger ages* OI surveillance HIV case reporting or advanced HIV case reporting ART outcomes Most at risk surveys HIV drug resistance ANC surveillance HIV infection Advanced HIVDeath *In epidemics where infection is driven by the general population Key HIV surveillance data points, 2009 and future Incidence Report early infant diagnosis Immunization surveys Mortality Vital registration Verbal autopsy HIV exposure HIV- free survival Population-based surveys*

5. Lack of HIV surveillance data for children Lack of HIV surveillance data for children Population-based surveys include persons 15-49 years, few countries have included children<15 Health facility surveys seldom include children Limited data on HIV-related morbidity in children Limited systematic measurement of PMTCT impact Mortality data are limited to infant mortality, neonatal mortality and peri-natal mortality and AIDS is seldom reported

6. Missed Opportunities for Prevention, Diagnosis, and Treatment for Children Globally, inadequate scale-up of effective PMTCT –Poor coverage HIV testing in ANC - 18% in 2008 –Few pregnant women with HIV get ARVs- 34% Poor linkage and lost to follow-up from PMTCT Lack of identification of HIV-infected children Small % of those who need ART are getting it Majority starting ART at an older age Low rates of retention in care and treatment

8. Need for Better Data New WHO Guidelines All infants should have HIV exposure status determined ideally before 6 weeks of age HIV-exposed infants should have viral test (HIV nucleic acid test) at 4-6 weeks of age Early initiation of ART for all HIV-infected infants regardless of clinical or immunologic stage significantly reduces risk of death and disease progression HIV testing recommended for any child presenting to health facilities with signs, symptoms or medical conditions that could indicate HIV

9. HIV Prevalence

10. 2.5 Children living with HIV globally, 1990-2007

11. UNAIDS estimates UNAIDS estimates based on modeling of data and assumptions, including: –HIV prevalence in adult women (ages 15-49) –Fertility rates –Survival of HIV-positive women –Childhood survival Population-based data collected among children has not yet informed these estimates

12. National Population-based Surveys With HIV testing Conducted in 25 countries since 2000 Data used to fill in gaps and improve estimation Recommended for high burden, generalized epidemics –Countries with prevalence <5% conducted surveys Some countries have conducted >1 survey Only three countries- Botswana, South Africa and Swaziland—have sampled children <15

13. Results Of Population-based Surveys In Three Southern African Countries Botswana 2004 –1.5-4 yrs 6.3% –5-9 yrs 6.0% –10-14 yrs 3.9% Swaziland 2007 –5-9 yrs4.2% –10-14 yrs2.6% South Africa 2002, 2005 –2-14 yrs Males 3.2% Females 3.5% Additional risk factor data collected –HIV status of mother and father –Receipt of PMTCT –Breast-feeding by biological mother and non-biological mother –Non MTCT risk factors, including sexual, nosocomial, etc

14. Population based Surveys with HIV Testing Challenges Should be conducted in high burden, generalized epidemics –consideration should be given to critical age groups to include (e.g., <2, 2-9, 10-14) Sample Size Considerations Logistics and expense HIV Counseling issues Ethical considerations –returning HIV test results

15. HIV Incidence

16. 2.6 New HIV infections among children 1990-2007

17. Table 1: Estimated number of pregnant women and children (0-14 years) living with HIV/AIDS in the PEPFAR focus countries Country Estimated number of HIV pos pregnant women, 2007, PEPFAR Estimated number of HIV pos pregnant women, 2007, UN Estimated number of children living with HIV/AIDS at end of 2007, UN Botswana15,6981100015,000 Cote d'Ivoire60,19228,00052,000 Ethiopia145,31466,00092,000 Guyana325<5001500 Haiti8,3395,1006,800 Kenya101,29076,000155,000 Mozambique136,96097,000100,000 Namibia10,4419,40014,000 Nigeria236,360190,000220,000 Rwanda15,12011,00019,000 South Africa352,640220,000280,000 Tanzania138,243100,000140,000 Uganda87,17278,000130,000 Vietnam6,6163,9003,800 Zambia89,30076,00095,000 All Countries1,404,010971,4001,324,100 Estimates of the number of infants born to HIV-infected mothers are critical for determining coverage and targets for infant testing and co- trimoxazole (CTX), however, there are discrepancies that need resolution between PEPFAR estimates presented in the table above, which use annual number of births and ANC prevalence, and modeled estimates from UNAIDS, which are much lower (971,400)

18. Systematic Measurement of PMTCT Impact Possible Population-based Approaches –PMTCT/EID Program Data –HIV Case Reporting –Immunization Clinic Surveys –Population-based DHS Surveys Several Proposed Outcome Measures –HIV-transmission rate –HIV-free survival (incorporates early and late transmission and survival benefits)

19. Possible Approaches to Measure Impact: PMTCT/EID Program Data, Botswana High coverage (>95%) of ANC, HIV testing, and delivery in a health facility 90% of HIV+ women receive at least some PMTCT intervention Impact can be described because of high coverage of PMTCT and successful early infant diagnosis program Estimated transmission rate to infants at 6 weeks is 25% with no program and <5% with PMTCT program

20. PMTCT coverage, Botswana

22. Limitations of Facility-based Program Data Difficult to obtain standard, representative data –Miss those who do not access services (ANC, L/D, etc) –Varying coverage of PMTCT and EID –Limited information on those who are lost to follow-up Data on PMTCT ARV regimens not generally available (new indicator) Misses women who seroconvert post-natally Sites may differ significantly in data quality and program performance Potential for duplicate counting National program data are difficult to obtain for surveillance use

23. Mother-to-Child Transmission Rate in 14 Surveillance Provinces, Thailand case-based surveillance P Akarasewi, presented at Second HIV Surveillance Meeting, Bangkik, 2009, at1 Bureau of Epidemiology, data analyzed date Feb 2009 Transmission Rate (%) NVP AZT mono HAART for CD4<200 AZT/NVP for CD4> 200 Definitive: HIV status determined by surveillance case definition Presumptive: definitive + assumed death Surveillance for perinatal HIV in 14 provinces since 2001 Decreased transmission with increase in PCR and decreased age at diagnosis Became part of routine system in 2005 Form of incident case reporting

24. Possible Approaches Immunization Clinic Surveys Measure “Incidence” of HIV among infants attending PHC for immunization services (EID) (cumulative effectiveness of PMTCT) Anonymous, unlinked testing survey conducted on infants attending immunization clinics at 6 weeks of age in 3 urban and 4 rural clinics in SA; mothers were asked for written informed consent and offered linked PCR testing for HIV for their infants HIV antibody testing (infant exposure status) with subsequent PCR testing-qualitative RNA assay (early infection rate) Mothers were asked outcomes of previous pregnancies to estimate infant and child mortality rates Estimated transmission rate was 20.2%, 7.5% of all 6 week old infants were HIV infected Subsequent survey had testing with informed consent, post-test counseling, and linkage to care and treatment for mother and baby Uptake 91%, acceptable and feasible in three clinics in South Africa Rollins, AIDS 2007; Rollins AIDS 2009

25. Possible Approaches: Modification of Population-based surveys to Measure Impact More detailed questions on PMTCT enrollment, interventions, infant feeding, and household child mortality Collected DBS from all children < 2 years (HIV exposure and infection status) Estimate HIV free survival= #born in last 2 yrs- (#infected +# died)/#born in last 2 yrs and transmission rate Consider addition of “verbal autopsy” interview for recent child deaths to approximate HIV-attributable infant mortality Use of adults in these surveys as index cases to identify infants for inclusion Stringer E, et al Bulletin of WHO; January 2008, 86 (1)

26. Morbidity

27. HIV prevalence and HIV testing in TB patients, worldwide, 2006: What about data for children? WHO. Global Tuberculosis Control 2008. Surveillance, Planning, Financing. % of notified TB patients tested for HIV: America – 32% Europe – 46% Africa – 22%

28. Incidence of Selected AIDS-Defining Condition, 1 Incidence of Selected AIDS-Defining Condition, 1992-2001, USA* Year HAART era 1992 Overall 13% 2001 Overall 2% *Pediatric spectrum of Disease project

29. Mortality

30. 2.7 Child Deaths due to AIDS, Globally, 1990-2007

31. Estimated impact of AIDS on under-5 child mortality rates – Selected African countries, 2010 Source: US Bureau of the Census 250 200 150 100 50 0 per 1000 live births with AIDS BotswanaKenyaMalawiTanzaniaZambiaZimbabwe without AIDS

32. Vital registration in Africa Mathers CD, Ma Fat D, Inoue M, Rao C, Lopez AD. Counting the dead and what they died from: an assessment of the global status of cause of death data. Bull World Health Org 2005;83:171-7.

33. Mortality Future Directions Lack of reliable cause of death information in vital registration systems contributes to significant gaps in mortality data –Need for improvement in overall vital registration Emerging models to measure cause of death –Verbal autopsy with strengthening of vital registration (SAVVY: sample vital registration with verbal autopsy-Zambia) –Morgue/burial surveillance –Hospital surveillance

34. Future Directions for HIV Surveillance in Children Need for Improved Pediatric surveillance –Burden of the epidemic in children to assess care & treatment needs, guide program planning –Impact of PMTCT programs on incidence, HIV free survival –Impact of care and treatment programs on mortality Expanded surveillance should include: –Sampling children in population-based surveys for high burden countries with generalized epidemics –HIV surveillance in health facilities (e.g. HIV testing during immunization visits) –Case-based surveillance registry (e.g. Thailand) –Improve HIV/AIDS mortality surveillance to more active efforts and improve overall vital registration –Improved OI surveillance (TB at a minimum) –ART outcomes and drug resistance monitoring among children –Linking surveillance data to risk behavior data (increased understanding of HIV risk exposure)

35. Future Directions for HIV Surveillance in Children Consider Regional Approaches –Harmonize approach at country level –Different approaches depending on burden of disease in children and phase of implementation of the program Understand ethical and other barriers to including children in these broader population-based surveys Use expansion of HIV surveillance to improve surveillance capacity for other child health programs Address gaps and needs for adolescent populations (population-based and most-at-risk populations-in and out of school youth) Strengthen use of surveillance data

36. Thank you O Shisana, HRSC T Rehle, HRSC S Patel, CDC E Kim, CDC T Goldman, CDC SA T Creek, CDC E Rivadeneira, CDC T Dinh, CDC SA N Rollins, WHO