1. Washington D.C., USA, 22-27 July 2012www.aids2012.org Turning the Tide on HIV/AIDS in Children and Youth Dr Chewe Luo, MD(Paed), MTropPaed, PhD Senior Programme Adviser HIV Section, UNICEF Programme Division New York

2. Washington D.C., USA, 22-27 July 2012www.aids2012.org Outline What does turning the tide mean? Eliminating new HIV infections in children Early diagnosis and treatment of HIV infected children Adolescent Prevention and Treatment Call to Action

3. Washington D.C., USA, 22-27 July 2012www.aids2012.org Key concepts in vertical transmission Transmission can occur during pregnancy, labor & delivery, and postpartum during breast feeding Not all infants born to women living with HIV will acquire HIV infection – Estimated risk 25-45% without any intervention TRANSMISSION TIMELINE Source: DeCock et al. JAMA.2000; 283:1175-1182.

4. Washington D.C., USA, 22-27 July 2012www.aids2012.org 67% Reduction in Perinatal Transmission with PACTG 076 AZT Regimen DSMB halted trial early in Feb 1994 Incidence of Perinatally-Acquired AIDS United States, 1985-2000 Source: www.cdc.gov/hiv/perinatal/resources

5. Washington D.C., USA, 22-27 July 2012www.aids2012.org Overall Target 1: Reduce the Number of New HIV Infections among children by 90% by 2015 Source: 1. UNAIDS. Together we will end AIDS. 2012 2. HIV/AIDS Response – Epidemic Update and Health Sector Progress Towards Universal Access 2011

6. Washington D.C., USA, 22-27 July 2012www.aids2012.org Overall Target 2: Reduce the Number of HIV- associated maternal deaths to women during pregnancy, delivery and puerperium by 50% by 2015 Source: UNAIDS. Together we will end AIDS. 2012

7. Washington D.C., USA, 22-27 July 2012www.aids2012.org Prevention of mother-to-child transmission of HIV: Body of scientific research 1994 U.S. AZT Trial ACTG 076 1998 Thai Bangkok short AP/IP AZT trial 1998 Cote d‘Ivoire short AP/IP AZT trials (breastfeeding) 1999 PETRA AZT+3TC trial (partly breastfeeding) 1999 Uganda 2-dose IP/PP NVP trial (HIVNET 012) 19942010 2000 Thailand PHPT-1 Long vs short AZT regimens 2002 Cote d’Ivoire DITRAME Plus 1201.0 AZT & IP/PP NVP 2004 Thailand PHPT-2 AZT & IP/PP NVP 2003 DITRAME Plus 1201.1 AZT+3TC & IP/PP NVP Source: McIntyre J, Perinatal HIV Clinical Trials 2008 PEPI NVP + short vs long AZT for infant (breastfeeding) 2009 Mma Bana comparative trial for CD4<200 (breastfeeding)

8. Washington D.C., USA, 22-27 July 2012www.aids2012.org Coverage of antiretroviral medicine for preventing mother-to-child transmission: most effective regimens, low- and middle-income countries, by region, 2011 Source: UNAIDS. Together we will end AIDS 2012

9. Washington D.C., USA, 22-27 July 2012www.aids2012.org The decline in new HIV infections in children was roughly 10.8% from 2010 to 2011 Source: 1. UNAIDS 2012 estimates 2. UNICEF/BLC Discussion Paper and Methodology - Business Case for Options B/B+, 2012

10. Washington D.C., USA, 22-27 July 2012www.aids2012.org Global Plan Targets Source: Countdown to zero: Global Plan towards the elimination of new infections among children by 2015 and keeping their mothers alive 2011-2015

11. Washington D.C., USA, 22-27 July 2012www.aids2012.org WHO guidelines for PMTCT and infant feeding (2010 and 2012 Update) Source: : 1. WHO 2010 PMTCT Guidelines 2. WHO Programmatic Update 2012

12. Washington D.C., USA, 22-27 July 2012www.aids2012.org PMTCT Prophylaxis Options Used by Selected Countries in Africa & Asia, 2012 Option A CameroonIndia* LesothoZimbabwe DRCMyanmar EthiopiaMalaysia Kenya*Vietnam MozambiqueSwaziland South Africa*Tanzania Uganda*Zambia* NigeriaAngola Namibia* Option B Bangladesh Afghanistan Bhutan Maldives Nepal Pakistan Sri Lanka Chad Burundi Botswana Cote D’Ivoire Ghana Rwanda Option B+ Malawi Source: www.aidsdatahub.org based on WHO, UNAIDS, & UNICEF (2011). Towards Universal Access Health Sector Response Country Reports 2011 (preliminary data) * Countries considering switch to option B/B+

13. Washington D.C., USA, 22-27 July 2012www.aids2012.org Potential Impact and Cost-Effectiveness of Scenarios “A” and “B” of the 2009 PMTCT Guidelines – 15 Focus Countries, 2010 Source: Auld AF et al. XVIII IAS Conf, Vienna, July 2010 Abs Model Outcome Scenario “2006” (95% CI) Scenario “A” (95% CI) Scenario “B” (95% CI) Infant HIV Infections (thousands) 345 (328-361)242 (231-252)258 (247-270) Infections Averted (thousands) 66 (50-82)169 (159-180)152 (141-163) Life-Years Gained (LYG millions) 1.3 (0.7-2.0)3.2 (2.7-3.6) 2.9 (2.4-3.4) Additional LYG (millions) -1.9 (0.8-2.9)1.6 (0.4-2.7) Cost (US $ millions)64 (55-73)235 (223-247)343 (325-362) Additional Cost (millions) -171 (150-192)288 (252-307) ICER (US $/LYG) -92 (81-107) Equally Effective More Expensive

14. Washington D.C., USA, 22-27 July 2012www.aids2012.org Bottlenecks in the implementation of Option A Source: UNICEF/BLC Discussion Paper and Methodology - Business Case for Options B/B+, 2012

15. Washington D.C., USA, 22-27 July 2012www.aids2012.org Women Eligible for ART Are At Highest Risk for Mother-to-Child HIV Transmission and Mortality Cohort 1,025 pregnant women in Zambia prior to HAART availability Analyzed MTCT/mortality by eligibility for ART with current WHO criteria (CD4 <350 or WHO Stage 3 or 4) Source: Kuhn L et al. AIDS 2010;24:1374-7

16. Washington D.C., USA, 22-27 July 2012www.aids2012.org Mortality risk in HIV-positive postpartum women with high CD4 Data: Hargrove AIDS 2010; Model: Williams JID 2006.

17. Washington D.C., USA, 22-27 July 2012www.aids2012.org Double Orphaning is projected to increase by 2016… Source: Belsey, M. A., L. Sherr. An International Interdisciplinary Journal for Research, Policy and Care; 6 (3):185-200.

18. Washington D.C., USA, 22-27 July 2012www.aids2012.org Rationale: Without CD4, women who need treatment for their own health will not receive appropriate ART with Option A Obtaining CD4 has been a barrier to PMTCT implementation in countries with heavily constrained health systems Prolonged breastfeeding up to 2 years High fertility rates with an average of 5.6 New potential benefit to uninfected sexual partners Malawi: Proposed “Option B+” Life-Long ART Lancet 2011;378:282-4

19. Washington D.C., USA, 22-27 July 2012www.aids2012.org Malawi : “Option B+” Scale Up Source: Courtesy of Dr Erik Schouten, unpublished data, Malawi Six-fold increase in number of pregnant & breastfeeding women starting ART (from 1200 in Q2 to 15,000 in Q4)

20. Washington D.C., USA, 22-27 July 2012www.aids2012.org Malawi: Progress on key indicators for the Global Plan for eliminating mother-to-child transmission Source:. 2012 UNAIDS estimates for Malawi: ARV/ART coverage among HIV+ pregnant women (Progress in 22 priority countries on key indicators for the Global Plan for eliminating mother-to-child transmission) * 2009 value is not directly comparable to data from 2010 and later because single-dose nevirapine was excluded from the calculation starting in 2010.

21. Washington D.C., USA, 22-27 July 2012www.aids2012.org Option B+ Benefits Source: UNICEF/BLC Discussion Paper and Methodology - Business Case for Options B/B+, 2012

22. Washington D.C., USA, 22-27 July 2012www.aids2012.org Comprehensive MCH Services

23. Washington D.C., USA, 22-27 July 2012www.aids2012.org Acute Infection in Mothers Associated with MTCT Risk of MTCT in infants of mothers with acute infection during pregnancy or lactation is increased ~3-fold over mothers with chronic HIV. Author Population Acute/recent HIV infection HIV Transmission to Infant Moodley D (JID 2011; 203:1231-4) 1,396 HIV- women/48 3.4% seroconverted pregnancy or by 12 mo PP 2.3-fold higher risk of MTCT (Overall MTCT 20.5% acute vs 9.0% chronic HIV) Taha TE (AIDS 2011 May 21 epub) 2,561 HIV+ women (PP) 2.9% had recent infection 2.5-fold higher risk in utero MTCT (In utero MTCT 17.8% acute vs 6.7% chronic HIV) Humphrey (BMJ 2010;341: c6580) 11,240 HIV- women 3.0% seroconverted postpartum 2.8-fold higher risk postnatal MTCT (Postnatal MTCT 23.6% acute vs 8.5% chronic HIV)

24. Washington D.C., USA, 22-27 July 2012www.aids2012.org Unmet Need for Family Planning Sources: UNAIDS calculations of data from Demographic and Health Surveys (MEASURE DHS: all surveys by country [web site] (25)) and Millennium Development Goals indicators [web site] (36). aThe difference between women living with HIV and HIV-negative women is statistically significant. Millenium Development Goals Indicators ( http://mdgs.un.org/unsd/mdg/data.aspx) Country and year of survey Unmet need among women living with HIV Unmet need among HIV- negative women Change in unmet need over time among all women Kenya 2008 21% 25% (2003) to 26% (2008) Lesotho 2009 16%18%31% (2004) to 23% (2009) Malawi 201018%21%28% (2004) to 26% (2010) Swaziland 200712%14%No comparison available Zambia 2007*14%20%27% (2002) to 27% (2007) Zimbabwe 200614%8%13% (1999) to 12% (2006) Unmet need for family planning by HIV serostatus based on data from Demographic and Health Surveys in six countries

25. Washington D.C., USA, 22-27 July 2012www.aids2012.org Percentage of children living with HIV receiving antiretroviral therapy in low- and middle- income countries, 2005, 2009, 2010, and 2011 Source: WHO, UNAIDS and UNICEF. Global HIV/AIDS Response: Epidemic Update and Health Sector Progress Towards Universal Access Progress Report 2011

26. Washington D.C., USA, 22-27 July 2012www.aids2012.org Violari et al.NEJM 2008 Children Initiating Treatment Immediately have better chance of survival

27. Washington D.C., USA, 22-27 July 2012www.aids2012.org Trends in pediatric age distribution at ART initiation (2005-2010) Source: McNairy M. et al. Retention of HIV+ Children on ART in ICAP-supported HIV Care and Treatment Programs. Paper # 959, 19th CROI, Seattle, USA 2012

28. Washington D.C., USA, 22-27 July 2012www.aids2012.org Follow up of infants testing positive via EID at Review Sites Source: UNICEF. EID Review Country Reports 2009

29. Washington D.C., USA, 22-27 July 2012www.aids2012.org Viral Load and EID Product Pipeline Source: UNITAID HIV/AIDS Diagnostic Landscape 2 nd Edition 2012

30. Washington D.C., USA, 22-27 July 2012www.aids2012.org Paediatric Antiretrovirals: simplified dosing formats and analysing their adverse events CHAPAS-1 trial PK sub-study 2007  FDA licensing CHAPAS-2 LPV/r liquid vs tablets vs sprinkles PK study CHAPAS-3 Looking at specific toxicities in children d4T vs AZT vs ABC Efavirenz 600mg 2 x 300mg 3 x 200mg 3TC/ZDV/N VP Baby 3TC/ABC Baby and Junior Source: Dr Gibb for the Chapas Trials

31. Washington D.C., USA, 22-27 July 2012www.aids2012.org In 2011, 36% of new HIV infections worldwide occurred in young people (ages 15-24) Source: UNAIDS., updated 2012 estimates.

32. Washington D.C., USA, 22-27 July 2012www.aids2012.org Increasing HIV Prevalence in Adolescents Source: 1. National Institute of Health (INS), National Institute of Statistics (INE) and ICF Macro. 2010. National Enquiry on HIV/AIDS Prevalence, Behavior Risks and Information in Mozambique 2009. 2. Shisana O et al. South African national HIV prevalence, incidence, behaviour and communication survey 2008: A turning tide among teenagers?

33. Washington D.C., USA, 22-27 July 2012www.aids2012.org Prevention and Treatment Interventions for Adolescents DECREASING VULNERABILITYDECREASING RISK 1.Enrollment and retention of girls in School 2.Skill-based health education 3.Decreasing gender-based violence 4.Increasing age of marriage 5.Ensuring that health services respond to the needs of adolescents 6.Social protection 7.Protection, legislation, enforcement 1.Testing 2.Treatment 3.Harm Reduction I.Condoms II.Needle Exchange 4.Male Circumcision 1.For today: Adolescents 2.For the future: Neonatal Interventions that should be supported whether or not there was and HIV epidemic for rights or equity Specific evidence-based interventions that decrease the risk of HIV among young people for HIV, rights and equity Source: UNICEF Making the Case for Adolescents, unpublished data, 2012

34. Washington D.C., USA, 22-27 July 2012www.aids2012.org Call to Action Simplify our programmatic approaches to allow integration of PMTCT/ART in maternal child health services at the lowest levels of care – to optimize treatment access, adherence and retention Introduce innovative approaches to expand provider initiated HIV testing to adolescents, pregnant women and their partners Expand early infant diagnosis and integrate paediatric HIV treatment and care at lower level facilities and child survival programs Collaborate with community groups, including women living with HIV, to enhance support to women and their families to maintain good adherence and retention in care and treatment Focus on how to effectively deliver high impact interventions to adolescent to achieve the best prevention and treatment benefits

35. Washington D.C., USA, 22-27 July 2012www.aids2012.org Acknowledgments Dr Elaine Abrams Dr Wafaa El-Sadr Dr Diana Gibb Dr Priscilla Idele Dr Susan Kasedde Malawi Ministry of Health Mr Craig McClure Dr Lynne Mofenson Mr Tyler Porth Dr Juliana Silva UNICEF Regional and Country Advisors Dr Rachel Yates

36. Washington D.C., USA, 22-27 July 2012www.aids2012.org Thanks to all women and children that inspire and guide the work we do!! Thank you!!