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

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

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Key concepts in vertical transmission

TRANSMISSION TIMELINE

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
Source: DeCock et al. JAMA.2000; 283:1175-1182.
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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
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Overall Target 1: Reduce the Number of New HIV Infections among children by 90% by 2015
Estimated new Pediatric Infections in Low and Middle Income Countries (LMICs)
450,000 400,000 350,000 300,000 250,000 200,000 150,000
2% 3% 5%
7%

Country Contribution to 390,000 Paediatric HIV Infections in LMICs in 2010

Nigeria 10% DRC

430,000 390,000 330,000

13%

29%

Uganda Malawi Kenya Mozambique

India
Tanzania Zimbabwe Ethiopia Other Priority Countries Other LMICs

100,000
50,000 0 New Infections 2009 New Infections 2010 New New Infections Infections 2011 2015 (Goal) 43,000

6% 7% 6% 6% 6%

Source: 1. UNAIDS. Together we will end AIDS. 2012 2 . HIV/AIDS Response Epidemic Update and Health Sector Progress Towards Universal Access 2011
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Overall Target 2: Reduce the Number of HIVassociated maternal deaths to women during pregnancy, delivery and puerperium by 50% by 2015
Women dying from AIDS-related causes during pregnancy or within 42 days of the end of pregnancy in the 22 priority countries 45,000 40,000 35,000 30,000 25,000 20,000 21,000 33,000 3% 3% 3% 5% 42,000 22 priority countries contribution to 33,000 HIV-associated maternal deaths in 2011 1% 1% 1% 2% 1% 1% 1% .500% .500%
Nigeria South Africa Tanzania Mozambique Uganda Kenya Malawi India Zimbabwe Zambia DRC Cameroon Cote D'Ivoire Ethiopia Ghana Angola Chad Lesotho Burundi Swaziland Namibia Botswana

20%

5%
15,000 5% 10,000 5%

12%

9% 7% 7% 7%

5,000
0 2005 2010 2015 (Goal)

Source: UNAIDS. Together we will end AIDS. 2012

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Prevention of mother-to-child transmission of HIV: Body of scientific research

1994
1994 U.S. AZT Trial ACTG 076
1998 Thai Bangkok short AP/IP AZT trial
Source: McIntyre J, Perinatal HIV Clinical Trials

2010

1998 Cote dIvoire short AP/IP AZT trials (breastfeeding) 1999 PETRA AZT+3TC trial (partly breastfeeding) 1999 Uganda 2-dose IP/PP NVP trial (HIVNET 012) 2000 Thailand PHPT-1 Long vs short AZT regimens 2002 Cote dIvoire DITRAME Plus 1201.0 AZT & IP/PP NVP 2003 DITRAME Plus 1201.1 AZT+3TC & IP/PP NVP 2004 Thailand PHPT-2 AZT & IP/PP NVP 2008 PEPI NVP + short vs long AZT for infant (breastfeeding) 2009 Mma Bana comparative trial for CD4<200 (breastfeeding)
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Coverage of antiretroviral medicine for preventing mother-to-child transmission: most effective regimens, low- and middle-income countries, by region, 2011
90% 80%

79%
70%

79%

72% 67% 61% 63% 57%

Percentage (%)

60% 50% 40% 30% 20% 10% 0%

27%

19%
6%
Sub-Saharan Eastern and Western and Latin America Latin America Africa Southern Central Africa and the Africa Caribbean Caribbean East, South and SouthEast Asia Eastern Europe and Central Asia North Africa and the Middle East All low- and middleincome countries

Source: UNAIDS. Together we will end AIDS 2012

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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
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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

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WHO guidelines for PMTCT and infant feeding (2010 and 2012 Update)

Source: : 1. WHO 2010 PMTCT Guidelines 2. WHO Programmatic Update 2012

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PMTCT Prophylaxis Options Used by Selected Countries in Africa & Asia, 2012
Option A
Cameroon India*

Option B
Bangladesh Afghanistan Bhutan Maldives Nepal Pakistan Sri Lanka Chad Burundi Botswana Cote DIvoire Ghana Rwanda

Option B+
Malawi

Lesotho
DRC Ethiopia Kenya* Mozambique South Africa* Uganda* Nigeria

Zimbabwe
Myanmar Malaysia Vietnam Swaziland Tanzania Zambia* Angola Namibia*

* Countries considering switch to option B/B+

Source: www.aidsdatahub.org based on WHO, UNAIDS, & UNICEF (2011). Towards Universal Access Health Sector Response Country Reports 2011 (preliminary data)
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Potential Impact and Cost-Effectiveness of Scenarios A and B of the 2009 PMTCT Guidelines 15 Focus Countries, 2010
Model Outcome Infant HIV Infections (thousands) Scenario 2006 (95% CI) 345 (328-361) 66 (50-82) Scenario A (95% CI) 242 (231-252) 169 (159-180) Scenario B (95% CI) 258 (247-270) 152 (141-163)

Infections Averted (thousands)

Life-Years Gained (LYG millions) Additional LYG (millions) Cost (US $ millions) Additional Cost (millions) ICER (US $/LYG)

1.3 (0.7-2.0)
64 (55-73) -

3.2 (2.7-3.6)
1.9 (0.8-2.9) 235 (223-247) 171 (150-192) 92 (81-107)

2.9 (2.4-3.4)
1.6 (0.4-2.7) 343 (325-362) 288 (252-307) Equally Effective More Expensive

Source: Auld AF et al. XVIII IAS Conf, Vienna, July 2010 Abs

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Bottlenecks in the implementation of Option A

Source: UNICEF/BLC Discussion Paper and Methodology - Business Case for Options B/B+ , 2012
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Women Eligible for ART Are At Highest Risk for Mother-to-Child HIV Transmission and Mortality
Eligible for ART MTCT by 6 wk Proportion of MTCT by 6 wks MTCT after 6 wks Proportion of MTCT after 6 wks Maternal mortality 24 mo post delivery 16.7% 87.5% 17.0% 87.5% 92% Not eligible for ART 5.0% 12.5% 4.2% 12.5% 8%

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
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Mortality risk in HIV-positive postpartum women with high CD4

Data: Hargrove AIDS 2010; Model: Williams JID 2006.

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Double Orphaning is projected to increase by 2016

Estimates of double orphans for 2010 and 2016
9.00% 8.00% 7.00% 6.00% 5.00% 4.00% 3.00% 2.00% 1.00% .00%

Double orphan prevalence 2010

Double orphan prevalence 2016

Source: Belsey, M. A., L. Sherr. An International Interdisciplinary Journal for Research, Policy and Care; 6 (3):185-200.
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Malawi: Proposed Option B+ Life-Long ART

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
Lancet 2011;378:282-4
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Malawi: Option B+ Scale Up

Number of pregnant and breastfeeding women starting ART
40000 35000 30000 25000

New patients starting ART Breastfeeding women starting ART Pregnant women starting ART

20000
15000 10000 5000 0 Q4 2011 Q1 Q2 Q3 Q4

Six-fold increase in number of pregnant & breastfeeding women starting ART (from 1200 in Q2 to 15,000 in Q4)
Source: Courtesy of Dr Erik Schouten, unpublished data, Malawi
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Malawi: Progress on key indicators for the Global Plan for eliminating mother-to-child transmission
Malawi: Percent of women provided antiretrovirals to reduce transmission during pregnancy and delivery (excl sdNVP)
60%

Malawi: Percent of pregnant women receiving antiretroviral therapy for their own health
60%

50%
50% 40% 30% 40%

30%

53%
20% 10% 0% 2009* 2011 20%

51%

24%

10%

12%
0% 2009 2011

* 2009 value is not directly comparable to data from 2010 and later because single-dose nevirapine was excluded from the calculation starting in 2010.
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)
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Option B+ Benefits

Source: UNICEF/BLC Discussion Paper and Methodology - Business Case for Options B/B+ , 2012

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Comprehensive MCH Services

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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 Moodley D (JID 2011; 203:1231-4) Population 1,396 HIVwomen/48 Acute/recent HIV infection 3.4% seroconverted pregnancy or by 12 mo PP 2.9% had recent infection HIV Transmission to Infant 2.3-fold higher risk of MTCT (Overall MTCT 20.5% acute vs 9.0% chronic HIV) 2.5-fold higher risk in utero MTCT (In utero MTCT 17.8% acute vs 6.7% chronic HIV) 3.0% seroconverted postpartum 2.8-fold higher risk postnatal MTCT (Postnatal MTCT 23.6% acute vs 8.5% chronic HIV)

Taha TE (AIDS 2011 May 21 epub) Humphrey (BMJ 2010;341: c6580)

2,561 HIV+ women (PP)

11,240 HIV- women

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Unmet Need for Family Planning

Unmet need for family planning by HIV serostatus based on data from Demographic and Health Surveys in six countries
Country and year of survey Unmet need among women living with HIV 21% 16% 18% 12% 14% 14% Unmet need among HIVnegative women 21% 18% 21% 14% 20% 8% Change in unmet need over time among all women 25% (2003) to 26% (2008) 31% (2004) to 23% (2009) 28% (2004) to 26% (2010) No comparison available 27% (2002) to 27% (2007) 13% (1999) to 12% (2006)

Kenya 2008
Lesotho 2009 Malawi 2010 Swaziland 2007 Zambia 2007* Zimbabwe 2006

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)
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Percentage of children living with HIV receiving antiretroviral therapy in low- and middleincome countries, 2005, 2009, 2010, and 2011
2005 2009 2010 2011

70% % of children younger than 15 years living with HIV receiving antiretroviral therapy

65% 61% 55% 46% 42% 42% 40% 39% 32% 31% 56%

60%

50%

40%

34%
30%

28%
17% 23% 21%

21% 20%
20%

26% 23%

10%

5%

6%

10% 9% 1%

12% 6% 4% 0%
East, South and South-East Asia Europe and Central Asia

5% 6%

0%
Sub-Saharan Africa Eastern and Western and Southern Africa Central Africa Latin America and the Caribbean Latin America Caribbean North Africa and Total low- and the Middle East middle-income countries

Source: WHO, UNAIDS and UNICEF. Global HIV/AIDS Response: Epidemic Update and Health Sector Progress Towards Universal Access Progress Report 2011
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Children Initiating Treatment Immediately have better chance of survival

Violari et al.NEJM 2008

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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
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Follow up of infants testing positive via EID at Review Sites

Source: UNICEF. EID Review Country Reports 2009

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Viral Load and EID Product Pipeline

Source: UNITAID HIV/AIDS Diagnostic Landscape 2nd Edition 2012

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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

3TC/ZDV/N VP Baby

3TC/ABC Baby and Junior

CHAPAS-3 Looking at specific toxicities in children

d4T vs AZT vs ABC

Efavirenz 600mg 2 x 300mg 3 x 200mg

Source: Dr Gibb for the Chapas Trials

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In 2011, 36% of new HIV infections worldwide occurred in young people (ages 15-24)

Source: UNAIDS., updated 2012 estimates.

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Increasing HIV Prevalence in Adolescents

South Africa: HIV Prevalence Among Adolescents and Young People Mozambique: HIV Prevalence Among Adolescents and Young People 20

25

20 Prevalence

15 Prevalence

15

10

10

5 5 0 2-14 Male Prev 15-19 Age 20-24 12-14 15-19 Age 20-24

Female Prev

Male Prev

Female Prev

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?
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Prevention and Treatment Interventions for Adolescents

DECREASING VULNERABILITY 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 Interventions that should be supported whether or not there was and HIV epidemic for rights or equity DECREASING RISK 1. Testing 2. Treatment 3. Harm Reduction I. Condoms II. Needle Exchange 4. Male Circumcision 1. For today: Adolescents 2. For the future: Neonatal

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
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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

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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

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Thanks to all women and children that inspire and guide the work we do!! Thank you!!
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