washington d.c., usa, 22-27 july 2012 turning the tide on hiv/aids in children and youth dr chewe...
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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
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
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.
Washington D.C., USA, 22-27 July 2012www.aids2012.org
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
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
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
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
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
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)
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)
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
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 (
%)
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
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
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
Washington D.C., USA, 22-27 July 2012www.aids2012.org
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+
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 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
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
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
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%
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.
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.
.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
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
Washington D.C., USA, 22-27 July 2012www.aids2012.org
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)
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* 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
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
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)
2,561HIV+
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)
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 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
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
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
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Violari et al.NEJM 2008
Children Initiating Treatment Immediately have better chance of
survival
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
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
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Viral Load and EID Product Pipeline
Source: UNITAID HIV/AIDS Diagnostic Landscape 2nd Edition 2012
Washington D.C., USA, 22-27 July 2012www.aids2012.org
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
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.
Washington D.C., USA, 22-27 July 2012www.aids2012.org
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?
Washington D.C., USA, 22-27 July 2012www.aids2012.org
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
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
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