Washington D.C., USA, 22-27 July 2012 Turning the Tide on HIV/AIDS in Children and Youth Dr Chewe...

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, PhDSenior Programme Adviser

HIV Section, UNICEF Programme DivisionNew York


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


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.


67% Reduction in Perinatal Transmission with

PACTG 076 AZT RegimenDSMB halted trial early in Feb 1994

Incidence of Perinatally-Acquired AIDS

United States, 1985-2000

Source: www.cdc.gov/hiv/perinatal/resources


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

New In

fect

ions

200

9

New In

fect

ions

201

0

New In

fect

ions

201

1

New In

fect

ions

201

5 (G

oal)

0

100,000

200,000

300,000

400,000430,000 390,000

330,000

43,000

Estimated new Pediatric Infec-tions in Low and Middle Income

Countries (LMICs)

29%

7%

7%

6%6%

6%

6%

5%

3%

2%

13%

10%

Country Contribution to 390,000 Paediatric HIV In-fections in LMICs in 2010

Nigeria

DRC

Uganda

Malawi

Kenya

Mozambique

India

Tanzania

Zimbabwe

Ethiopia

Other Priority Countries

Other LMICs


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

2005 2010 2015 (Goal)0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

40,000

45,000 42,000

33,000

21,000

Women dying from AIDS-related causes during pregnancy or within 42 days of the end of pregnancy in the 22 priority coun-

tries

20%

12%

9%

7%7%

7%

5%

5%

5%

5%

3%

3%

3%

2%

1%1%1% 1% 1% 1% 1% 1%

22 priority countries contribution to 33,000 HIV-associated maternal deaths

in 2011 NigeriaSouth AfricaTanzaniaMozambiqueUgandaKenyaMalawiIndiaZimbabweZambiaDRCCameroonCote D'Ivoire EthiopiaGhanaAngolaChadLesothoBurundiSwazilandNamibiaBotswana


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)

1994 2010

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 H

IV Clinical Trials

2008 PEPI NVP + short vs long AZT for infant (breastfeeding)

2009 Mma Bana comparative trial for CD4<200 (breastfeeding)


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

Sub-

Saha

ran

Africa

East

ern

and

Sout

hern

Afri

ca

Wes

tern

and

Cen

tral A

frica

Latin

Am

erica

and

the

Carib

bean

Latin

Am

erica

Carib

bean

East

, Sou

th a

nd S

outh

-Eas

t Asia

East

ern

Euro

pe a

nd C

entra

l Asia

North

Afri

ca a

nd th

e Mid

dle

East

All lo

w- a

nd m

iddl

e- in

com

e co

untri

es

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

61%

72%

27%

67% 63%

79%

19%

79%

6%

57%

Perc

enta

ge (

%)


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


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


WHO guidelines for PMTCT and infant feeding

(2010 and 2012 Update)

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


PMTCT Prophylaxis Options Used by Selected Countries in Africa & Asia,

2012Option A

Cameroon India*

Lesotho Zimbabwe

DRC Myanmar

Ethiopia Malaysia

Kenya* Vietnam

Mozambique Swaziland

South Africa* Tanzania

Uganda* Zambia*

Nigeria Angola

Namibia*

Option BBangladesh

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+


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 OutcomeScenario “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


Bottlenecks in the implementation of Option A

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


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

Eligible for ART

Not eligible for ART

MTCT by 6 wk 16.7% 5.0%

Proportion of MTCT by 6 wks

87.5% 12.5%

MTCT after 6 wks

17.0% 4.2%

Proportion of MTCT after 6 wks

87.5% 12.5%

Maternal mortality 24 mo post delivery

92% 8%


Mortality risk in HIV-positive postpartum women with high CD4

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


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.

.000%

1.000%

2.000%

3.000%

4.000%

5.000%

6.000%

7.000%

8.000%

9.000%

Estimates of double orphans for 2010 and 2016

Double orphan prevalence 2010 Double orphan prevalence 2016


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


Malawi: “Option B+” Scale Up

Source: Courtesy of Dr Erik Schouten, unpublished data, Malawi

Q4 2011 Q1 Q2 Q3 Q40tan28a566028

0tan6a56736

0tan16a568716

0tan25a570125

0tan6a57156

0tan15a572815

0tan25a574225

0tan4a57564

0tan14a576914

Number of pregnant and breastfeeding women starting ART

New patients starting ART

Breastfeeding women starting ART

Pregnant women starting ART

Six-fold increase in number of pregnant & breastfeeding women starting ART

(from 1200 in Q2 to 15,000 in Q4)


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* 20110%

10%

20%

30%

40%

50%

60%

24%

53%

Malawi: Percent of women provided antiretrovirals to re-

duce transmission during pregnancy and delivery (excl

sdNVP)

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

0tan28a566528 0tan30a5665300%

10%

20%

30%

40%

50%

60%

12%

51%

Malawi: Percent of pregnant women receiving antiretroviral

therapy for their own health


Option B+ Benefits

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


Comprehensive MCH Services


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)

2,561HIV+

women (PP)

2.9% had recent

infection

• 2.5-fold higher risk in utero MTCT

(In utero MTCT17.8% acute vs 6.7% chronic HIV)

Humphrey (BMJ 2010;341: c6580)

11,240HIV-

women

3.0% seroconverted postpartum

• 2.8-fold higher risk postnatal MTCT

(Postnatal MTCT23.6% acute vs 8.5% chronic HIV)


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 200821% 21% 25% (2003) to 26% (2008)

Lesotho 200916% 18% 31% (2004) to 23% (2009)

Malawi 2010 18% 21% 28% (2004) to 26% (2010)

Swaziland 2007 12% 14% No comparison available

Zambia 2007* 14% 20% 27% (2002) to 27% (2007)

Zimbabwe 2006 14% 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


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

0%

10%

20%

30%

40%

50%

60%

70%

5% 6%1%

34%

42%

6%12%

17%

0%6%

20%23%

10%

55%61%

32%

40%

56%

4%

21%21% 26%

9%

42%46%

31%

39%

65%

5%

23%

12tan28a566028

2005 2009 2010 2011

% o

f ch

ild

ren

you

ng

er

than

15 y

ears

liv

ing

w

ith

HIV

receiv

ing

an

tire

trovir

al th

era

py


Violari et al.NEJM 2008

Children Initiating Treatment Immediately have better chance of

survival


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


Follow up of infants testing positive via EID at Review

Sites

Source: UNICEF. EID Review Country Reports 2009


Viral Load and EID Product Pipeline

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


Paediatric Antiretrovirals: simplified dosing formats and analysing their

adverse eventsCHAPAS-1 trialPK sub-study 2007FDA licensing

CHAPAS-2 LPV/r liquid vs tablets vs sprinkles PK study

CHAPAS-3 Looking at specifictoxicities in children

d4T vsAZT vs

ABC

Efavirenz 600mg

2 x 300mg3 x 200mg

3TC/ZDV/NVP Baby

3TC/ABC Baby and Junior

Source: Dr Gibb for the Chapas Trials


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

15-24)

Source: UNAIDS., updated 2012 estimates.


Increasing HIV Prevalence in Adolescents

2-14 15-19 20-24 0tan28a566028

0tan4a56604

0tan9a56609

0tan14a566014

0tan19a566019

0tan24a566024

South Africa: HIV Prevalence Among Adolescents and Young

People

Male Prev Female PrevAge

Pre

vale

nce

12-14 15-19 20-240tan28a566028

0tan4a56604

0tan9a56609

0tan14a566014

0tan19a566019

Mozambique: HIV Prevalence Among Adolescents and Young

People

Male Prev Female Prev

AgeP

reva

len

ce

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?


Prevention and Treatment Interventions for Adolescents

DECREASING VULNERABILITY DECREASING RISK

1. Enrollment and retention of girls in School

2. Skill-based health education3. Decreasing gender-based

violence4. Increasing age of marriage5. Ensuring that health

services respond to the needs of adolescents

6. Social protection7. Protection, legislation,

enforcement

1. Testing2. Treatment3. Harm Reduction

I. CondomsII. Needle Exchange

4. Male Circumcision1. For today: Adolescents2. 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


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


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


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

Thank you!!

Washington D.C., USA, 22-27 July 2012 Turning the Tide on HIV/AIDS in Children and Youth Dr Chewe...

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