Where Are We Headed with Paediatric Prevention and Treatment Shaffiq Essajee Melbourne, July 25 2014.

Where Are We Headed with Paediatric Prevention and Treatment

Shaffiq EssajeeMelbourne, July 25 2014

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 20130

100,000

200,000

300,000

400,000

500,000

600,000

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Trends in new HIV infections among children (aged 0-14) and coverage of maternal ARVs form PMTCT in all

low- and middle-income countries, 2001-2012

Maternal ARVs for PMTCTNew HIV infections in children (0-4)

Ne

w H

IV in

fec

tio

ns

(#

) PM

TC

T c

ov

era

ge

Source: UNAIDS 2013 HIV and AIDS estimates, 2014, and UNAIDS/WHO/UNICEF Global AIDS Response Progress Reporting (GARPR)/Universal Access data, 2006-2014

Global progress on PMTCT continues despite shrinking resources for HIV scale up

As maternal ARV access has increased, so the estimated number of new child infections has fallen to 240,000

Source: UNAIDS 2013 HIV and AIDS estimates, 2014, and UNAIDS/WHO/UNICEF Global AIDS Response Progress Report Universal Access data, 2006-14

Option B or B+ has now been adopted in all the 22 priority Global Plan countries, but the pace of implementation needs to increase

Globally close to 80% of countries have adopted Option B or B+ in their national program

Data

Option BB+ planning, piloting, early implementationB+ scale-upB+ national implementation

Missing Value

Source: lATT/WHO Global Update on the Health Sector Response to HIV, 2014.

There are 60% fewer new infections in children but there has not been a commensurate decline in child deaths

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 20130

100000

200000

300000

400000

500000

600000

700000

HIV-related child deaths

New Child infections from MTCT

60% reduction in new infections from peak of 580,000 per year 40% reduction in mortality from peak of 330,000 per year

Source: UNAIDS 2013 HIV and AIDS estimates, 2014, and UNAIDS/WHO/UNICEF Global AIDS Response Progress Report /Universal Access data, 2006-14

Unlike paediatric prevention, paediatric treatment efforts are stagnating especially when compared with adult coverage

• The denominator has increased – now “All people living with HIV” not “People in need of ART”

• Coverage for The gap between adult and child coverage has widened.

2007 2008 2009 2010 2011 2012 20130%

10%

20%

30%

40%

50%Paediatric ARTAdult ART

Percent (%)

Source: UNAIDS/WHO/UNICEF 2008-2014 GARPR/Universal Access reporting and UNAIDS 2013 HIV and AIDS estimates

38%

24%

We have been failing to achieve equity for children for a long time, but the situation today is different to the past

We don’t have the right drugs and formulations to treat children…

We still need a child friendly heat stable form of lopinavir/ritonavir but this is coming soon…

FDA approval

WHO PQ approval

Cost pppy

d4T/3TC 6/30mg 2008 2011 $46

d4T/3TC/NVP 6/30/50mg 2007 2008 $55

AZT/3TC 60/30mg 2007 2009 $72

AZT/3TC/NVP 60/30/50mg 2010 2009 $96

ABC/3TC 60/30mg 2011 2014 $168

EFV 200mg tab 2010 2009 $37

Yes we do!

Source: CHAI Ceiling Price 2013


It’s too complicated to treat children, you need specialists just to do the dosing….

WHO guidelines offer simplified harmonized weight band doses for all ages and all forms

No it isn’t

Drug

Children 6 weeks of age and aboveNumber of tablets by weight band

3-5.9kg 6-9.9kg 10-13.9kg

14-19.9kg

20-24.9kg

am pm am pm am pm am pm am pm

AZT dual 1 1 2 1 2 2 3 2 3 3AZT triple 1 1 2 1 2 2 3 2 3 3ABC dual 1 1 2 1 2 2 3 2 3 3d4T dual 1 1 2 1 2 2 3 2 3 3d4T triple 1 1 2 1 2 2 3 2 3 3Triple nucl 1 1 2 1 2 2 3 2 3 3LPV/r NR NR 2 1 2 2 3 2

Source: Adapted from WHO Consolidated guidelines 2013

We cant make an HIV diagnosis in infants because virological testing is too difficult


80,000

1,200,00015x increase

Year -

200,000

400,000

600,000

800,000

1,000,000

1,200,000

1,400,000

2007 2008 2009 2010 2011

Number of PCR tests each year

Global AIDS Report notes that 44% of infants are accessing an EID test within 2 months of life and in many countries this is above 90%

Source: CHAI UNITAID Program data 2012

Yes we can!

Five issues stand out as key bottlenecks across the continuum of care from diagnosis to treatment

We are not looking in the right places to identify HIV infected children.

When we do find infected children many are lost before enrollment into care

We are stalling in efforts to expand pediatric access though decentralization and task shifting

Diagnosis

LinkageTreatm

ent

1

2

3

4

5

We are not integrating paediatric HIV and MCH

We have failed to harness the community as a partner

for pediatric scale up

Diagnosis




Diagnosis

LinkageTreatm

ent

1

2

3

4

5




Globally paediatric testing is focused on infant diagnosis within PMTCT, but in the era of B+ are we looking in the right places? 1

Art Clinic EID Lab Maternity MCH/PMTCT/

ANC

OPD Outreach Paediatric Ward

PNC YCC/Im-munisa-

tion

Art Clinic EID Lab Maternity MCH/PMTCT/

ANC

OPD Outreach Paediatric Ward

PNC YCC/Im-munisa-

tion

No of test

2942 5972 813 1492 2372 1289 31 115 1600 1720

% Posi-tive

7 8 9 6 5 15 16 28 5 7

500

1500

2500

3500

4500

5500

6500

3

8

13

18

23

28

7 8 96 5

15 16

28

5 7

No of test % Positive

Inpatient wards

Source: Uganda national EID testing program statistics 2012

OPD testing of sick infants and outreach to infants whose mothers

were lost to follow up of from PMTCT8% of tests

16% of

pos

In Malawi, where B+ has been in place longest, National Program data confirm the shifting trend of paediatric HIV prevalence

Population Prevalence Source

HIV-exposed 6 week (DNA PCR) 2%National Supervision data, Q1 2014

HIV-exposed 12 month 6%National Supervision data, Q1 2014

Moderately malnourished children in outpatient rehabilitation

6.6%Nutrition program (5 months in 2014 in16/28 districts)

Moderate-severely malnourished children in outpatient rehabilitation

18%Nutrition program (5 months in 2014 in 16/28 districts)

Severely malnourished children in inpatient rehabilitation

23%Nutrition program (5 months in 2014 in16/28 districts)

1

Source: Malawi Ministry of Health 2014

Testing in inpatient or outpatient settings can identify older children and infants who “slip through the cracks” of PMTCT 1

Approach AcceptabilityHIV exposed or

infectedImpact

Rollins et al. AIDS 2009

Routine HIV Ab screening with follow up EID testing of infants in 3 immunization clinics in KZN

90% of mothers accepted infant testing

>40% of infants had HIV exposure9.2% were DNA PCR positive

No impact on immunization rates

McCollum et al. Plos One 2010

Routine inpatient screening in Lilongwe of mother and child

71% of mothers accepted child testing

8.5% were infected

Testing was also offered to mothers with good acceptance

Mutanga et al. PLOS One 2012

Routine inpatient in Lusaka using HIV Ab tests

98% acceptance of testing

15.5% infected >90% linkage to services as in a large general hospital

Recommendations & policy guidance exist for PITC in children in generalized epidemics, but they are rarely implemented 1

• PITC Eligibility: All children 6-15 with unknown status

• Sites: 6 primary clinics in Harare over a 4-month period

• 2,831 children eligible but only 70% were offered a test

• Reasons for not testing

• Unsuitable guardian – especially male guardians

• Lack of staff time or reagents

• Child “did not seem sick” or was “too old to have HIV”

• 90% of children tested could have received PITC earlier

Kranzer et al. PLOS one 2014

Loss to follow up and Linkage




Diagnosis

LinkageTreatm

ent

1

2

3

4

5




In this 4-country retrospective review, between 62 and 74% of positive infants could not be accounted for after 1 year

Source: Chatterjee et al. BMC Public Health, 2011. Collins et al. CROI 2014.

2

Positive

via EID

Receive

d Results

Enrolle

d in H

IV care

Initiated on ART

Alive and a

ctive

on ART0

500

1000

1500

2000

2500

3000

3500

64%

Retention of infected infants in Uganda

Each positive infant identified costs an estimated $240 to $440 depending on vertical transmission rates

Strategies such as SMS printers to return results to clinics have already been shown to improve infant retention

14 days

DBS drawn for PCR

6 wks 10 wks

Caregiver returns for

results

EID sample received at laboratory

Sample processed

Laboratory can immediately

send results via SMS printers5 -10

days

Results are available when

caregiver returns

2

POC offers “while you wait results” so may improve both clinical outcomes and reduce wastage of resources

1 2 3

• 827 HIV-exposed infants tested using Poc EID and traditional DNA PCR

• 60% of infants were between 1-2 months of age.• Overall 85 positive samples by DNA PCR, with

excellent correlation (only 2 samples were discordant) and sensitivity = 98.5%, specificity = 99.9%

• PoC gives rapid results AND is very portable allowing for use where needed – eg in labour ward or in community settings

2

Source: Jani et al. JAIDS 2014

Decentralization and Task shifting




Diagnosis

LinkageTreatm

ent

1

2

3

4

5

We are not integrating paediatric ART with MCH



Among 1740 South African children on ART, 18 month outcomes were the same in all tiers of the health system

Bock et al. Trans R Soc Trop Med Hyg 2008;102:905-911

Viral suppression

Mortality

CD4 Recovery

3

While task sharing in adults is well-established, for children despite evidence, national programs have been slow to adopt

Source: Penazzato et al. JAIDS 2014

Non-physician managed ART compared with physician managed ART

Mortality and retention outcomes from 6 to 36 months of follow up were comparable

3

Integration of paed HIV and MCH




Diagnosis

LinkageTreatm

ent

1

2

3

4

5




A pilot program in Uganda has had success in retaining mother-baby pairs by providing an integrated package of HIV services 4

• 22 MCH clinics at sites where ART is also available• MCH nurse-midwives trained in maternal and paediatric HIV care• Mothers and infants referred in from multiple entry points (including the ART clinic)

HIV Service packageMaternal ART (B+)

Infant CotrimoxazoleInfant NVP prophylaxis

Infant diagnosisFixed F/U appointment

MCH service packageNutritional assessment

Infant feeding counseling Immunization

Growth monitoringFP services

0%10%20%30%40%50%60%70%80%90%

100%Percentage at all 22 sites

0

500

1000

1500

309

1105

Number of mother-baby pairs seen in all 22 clinicsNumber of mother-baby pairs seen in all 22 clinics

USAID Applying Science to Strengthen and Improve SystemsSource: Nsubuga-Nyombi et al. TUSA03 AIDS 2014

COORDINATION CONTINUITY

Finding the balance between horizontal versus vertical service delivery systems 4

Involving the Community




Diagnosis

LinkageTreatm

ent

1

2

3

4

5




The Tingathe Program was piloted at 3 sites between 2008 and 2011 and showed marked improvement in case-finding

Mar

-07

Jun-

07

Sep-0

7

Dec-0

7

Mar

-08

Jun-

08

Sep-0

8

Dec-0

8

Mar

-09

Jun-

09

Sep-0

9

Dec-0

9

Mar

-10

Jun-

10

Sep-1

0

Dec-1

00

500

1000

1500

2000

2500

3000

Infected ever enrolled

Exposed ever enrolled

Total ever enrolled

Start of Tingathe BASIC

Start of Tingathe PMTCT

Date of clinic enrollment

Pa

tie

nt

Nu

mb

ers

5

Community health workers specialized in HIV testing & counseling, active case identification, PMTCT support, and linkage to care

Now expanded to 6 districts in central Malawi

Source: Ahmed et al. Manuscript submitted for publication

Conclusions

• We have the tools we need we just need to shed our complacency

• Our approach to finding infected and exposed children needs to go beyond PMTCT and reinvigorate PITC for children

• Solutions are local as much as global. No one size fits all for concepts like integration, community involvement and task shifting

• Even as we push for elimination of new infections in children we must also push to treat all children in need. There can be no dichotomy between treatment and prevention.

Acknowledgements

Chewe LuoCraig McLureSubhasree RaghavanLynne MofensenElaine AbramsSaeed AhmedMartina PenazzatoNathan FordNigel RollinsNandita SugandhiCharles KiyagaAnisa GhadrshenasPolly ClaydenAshraf GrimwoodJohn MillerStuart KeanTamara Nsubuga-Nyombi

Where Are We Headed with Paediatric Prevention and Treatment Shaffiq Essajee Melbourne, July 25 2014.

Documents

isntdrug children

global progress

hiv diagnosis

child coverage

option b

aids estimates38

long time

need of art coverage