Presented By

DR A K Gupta, MD (Pediatrics)Additional Project Director

Delhi State AIDS Control SocietyGovt of Delhi

2

This presentation will:Recapitulate Key concepts in diagnosing HIV infection in infants and young childrenExplain the National algorithms for diagnosing HIV in infants and young children Review the Performance of EID programme Discuss Lessons Learnt/Challenges / Issues which need to be addressed Explain new strategy to ensure enrollment of all new HIV exposed for EID Inform about Scale up of EID programme during 2012-13 Discuss Effectiveness of current PMTCT Interventions Explain Adapting WHO (2010) PMTCT protocol

Recapitulate Key concepts of EID

Children constitute:

10% of new HIV infections each yearo (280,000 out of 2.7 million)

6% of the persons living with HIVo (2 million out of 33 million)

13% of HIV/AIDS deaths each year o (270,000 out of 3 million)o 90% in sub-Saharan Africa

Source- UNAIDS, 2008

4

Rapid HIV progression and higher risk of death in infected infants

CD4 and viral load are poor predictors of disease progression in infants

Without Anti Retroviral treatment:

By age 1, one-third of all HIV-infected children will have

Died

By age 2, half of all HIV-infected children will have died

6

1 Year = 35%

mortality

2 Years = 53%

mortalityNewell ML Newell ML et al Lancet 2004; 364: 1236-43

From the Children with HIV Early Antiretroviral Therapy Study (CHER), Violari, NEJM 2008

7

The results of CHER trial demonstrated that early ART in HIV Infected Infants < 12 weeks of age reduced mortality by 76% and HIV progression by 75%.

All infants under 24 months of age with confirmed HIV infection should be started on antiretroviral therapy, irrespective of clinical or immunological stage.

No infant or maternal

ARV exposure

MTCT ARV Exposure

Sd NVP or NNRTI containing ART

Non NNRTI exposure

Unknown infantmaternal MTCT

Exposure

NVP triple ART

PI triple ART#

NVP triple ART

NVP triple ART

# If no PI is available use NVP triple ART

http://www.who.int/hiv/paediatric/en/index.html

10

To identify the HIV-infected child early, prior to the development of clinical disease during the first months of life. The goal is NOT to exclude infection in infants.

Diagnosis should be early enough so interventions and Anti Retroviral treatment can be started

Start ART in all confirmed HIV Infected infants irrespective of clinical or immunological status to reduce pediatric mortality and morbidity

Methods of Early Infant diagnosis

12

0

10

20

30

40

50

60

70

80

90

100

% antibody positive

birth 1 3 6 9 12 15 18

months of lifeMoodley D, PIDJ 1995;14:850

Rapid Ab can be used to exclude infection

around 12-18 months of age

13

0102030405060708090

100

sensitivity %

48 hrs 2-7 days 7-14 days 28 days

days

Dunn D, AIDS 1995, 9:F7

At 4-6 weeks of age sensitivity of

DNA PCR is 96-98%

Limitations of RNA PCR for Infant Diagnosis

Point-of-Care Testing for Early Infant Diagnosis

a. Whole blood from pricking skin, Dried on filter paper

b. Easy to store & Easy to transport

c. Required supplies for DBS collectionGlovesPenLab formsDBS cardLancet or glucoletDisinfectant for skinGauze or cotton wool

1. Warm the area2. Wash hands, put on gloves3. Position baby with foot

down4. Clean area, dry 30 sec5. Press lancet into foot, prick

skin6. Wipe away first drop7. Allow large drop to collect8. Touch blood drop to card9. Fill entire circle with drop10. Fill at least 3 circles11. Clean foot, no bandage

<5kg infants

5-10kg infants

Overhead 4-5

Overhead 4-34

circles not filled

clotted/layered

Scratched/abraded

Not Dried before sending

Serum Ring around

Don’t touch or smear the blood spots.Allow the specimen to air dry horizontally

for at least 3 hours. Keep away from direct sunlight, dust, and

bugs.Do not heat, stack or allow DBS to touch

anything during the drying process. Lay them on a flat surface or drying rack.

Add desiccant packets(minimum 10 packets per bag)

Add humidity card, press air out of bag, and seal bag

Keep packaged DBS (in sealable plastic bags) refrigerated until transported to reference laboratory.

Shipping

HOW TO PACKAGE & TRANSPOPRT DBS CARD

23

At 4-6 weeks of life or

At first visit (if >6 weeks of age)

Why at six weeks of age?The sensitivity of the test is > 96%Testing at this 4-6 weeks of age should identify

all babies infected in during pregnancy, labor & delivery and during early breast feeding

It correspond to first immunizations visit Cotrimoxazole prophylaxis is initiated at this age.

In 2007:

• only 8% of HIV exposed infants tested in 1st 2 months of life

• only 4 % started on co-trimoxazole

Towards Universal Access: Scaling up priority HIV/AIDS interventions in the health sector, WHO/UNAIDS/UNICEF 2008

17

47

23

76

30

78

0

10

20

30

40

50

60

70

80

90

Number of countries using dired bloodspots for virological testing

Number of countries with a policy onprovider initated testing and counselling for

infants and young children

2005 n=79

2006 n=108

2007 n=109

Missed Opportunties for Early Infant Diagnosis

Low weight and/or growth failure

Pneumonia, including PCP

Oral candidiasis (thrush) after 6 weeks of age

LymphadenopathyParotid gland

swellingRecurrent ear

infectionsPersistent

diarrhoeaTuberculosis

Risk of transmitting HIV to the infant during breastfeeding is greater when: The woman has a high viral load or low CD4 count (new infection or advanced HIV disease)

The woman has mastitis, a breast abscess, nipple sores or other breast problem

The infant or child has ulcers or open sores in the mouth

The child is mixed fed

Mixed feeding in first 6 months increases risk of HIV- If breastfed infant is given formula, risk doubles

- If breastfed infant is given solid foods the risk of HIV infection is eleven times as high as the exclusively BF infant

To minimize risk of MTCT, HIV-infected mothers should discontinue breastfeeding when infant is 6 months of age, if replacement feeding is AFASS

Transition from breast milk to replacement feeding should take place over 2-3 days to 2-3 weeks

33

Pneumocystis Jiroveci Pneumonia (PCP) is a severe and rapidly progressive pneumonia in HIV infected infants Peak incidence is between 3-6 months

Prophylactic cotrimoxazole therapy significantly reduces the risk of PCP, other bacterial infections and malaria and reduces infant deaths.

The CPT should be given from 6 weeks onwards to the weight of the infant/Child.

Give CPT until HIV has been ruled out and mother is no longer breast feeding

In BF - dispersed in expressed breast milk. In RF- disperse in 1-2 TSF of boiled water

Weight( Kg) Child dispersible tablets( 20mg TMP/100mg smx) X Once daily

<5 1 tablet

5-10 2 tablet

10-15 3 tablet

15-22 4 tablet

35

CTX is generally very well tolerated in children Check for tolerance and adherence at every visit

Side effects and toxicities are more common in Adults > children Advanced disease > early stages of disease

HIV-infected > HIV-exposed childrenIf a child develops severe reaction to CTX

Dapsone can be used for prophylaxis (2mg/kg/dose daily, maximum 100mg daily)

Reviw of Performance of EID programme during 2011-12

What proportion of pregnant women testing HIV+ get their HIV-exposed infants tested and at what age?

How long does it take for an EID sample to reach the lab, and for the result to reach the site? the family?

Among HIV-exposed infants receiving EID testing, what percent of mothers/caregivers receive their infant’s result?

Among all confirmed HIV-infected infants, what proportion initiates ART and at what age?

Among those initiated ART, proportion initiated correct regimen as per National Guidelines?

What proportion of pregnant women testing HIV+ get their HIV-exposed infants tested

and at what age?

How long does it take for an EID sample to reach the lab, and for the result to reach the site?

Among HIV-exposed infants receiving EID testing, what percent of mothers/caregivers receive their infant’s result?

9 (37.5%) Confirmed HIV positive infants LFU

51 (25.5%) DBS DNA PCR negative infants LFU

9 DBS DNA PCR Positive infants died before Whole Blood PCR Test

Among all confirmed HIV-infected infants, what proportion initiates ART and at what age?

15/24 (62.5%) confirmed HIV Infected Infants Initiated on Anti Retroviral Treatment

Nine (37.5%) children could not be initiated ART. -One Died in pre-ART, -6 were LFU -2 parents refused

Delayed start of ART resulted in OIs in 5/15 (33.3%) children

None of infant could beinitiated ART by 3 months of age

In 3 infants tested at 6 weeks of age ART was initiated at 4 mth, 9 mth and 11 mth of age.

Among those initiated ART, proportion initiated correct regimen as per National

Guidelines?

1. When HIV-1 is transmitted despite PMTCT with > 2 ARV drugs, or mother's ART, prevalence of NRTI or NNRTI resistance in infant HIV will be > 30%.

2. When HIV-1 is transmitted despite PMTCT with NVP alone, the prevalence of major mutations associated with NNRTI resistance in infant HIV will be 50% or greater

3. NNRTI Resistance may decrease with time by 20% in many infants after a long period of non-exposure to ARVs.

Source- Diane Bennett et al, Global AIDS Programme , CDC Atlanta

WHO 2010 Revised Guidelines for EID and ART

Ensuring Entry of all HIV exposed infants in the EID cascade

Ensuring testing at 6 weeks of age of all HIV exposed infants to serve the very purpose of EID

Training of pediatric providers on PICT and referral of symptomatic cases who missed opportunity of EID.

Reducing Turn Around Times of DNA PCR testing- change in national guideline of only 2 days /month of sending samples to reference lab.

Better coordination between ICTC and ART centers regarding NVP exposure status

Improving follow up of BF first DBS negative exposed infants

Early Initiation of ART in confirmed HIV infected infants before signs / symptoms of HIV develop ie by 12 weeks of age

Scale up of EID programme during 2012-13

Exisitng and New facilities

Strategy to Address the issues

Ensuring Adherence to CPT

Day 1-3 : Ensure first DBS DNA PCR test at 6 weeks of age & Send sample to NCDC within 2 days (ICTC/PPTCT)

Day 31/32: ART Centre call parents to start ART in confirmed HIV +ve infants within 7 days ie < =12 weeks of age

Day-10 Ensure result of DBS test is collected within 7 days of test (ICTC/PPTCT)

Day-17 Ensure infant reaches ARTC for Whole Blood Test (ICTC/PPTCT)

Day -17/18: Ensure whole blood sample is collected and sent to NCDC on same day

Day 23/24: ARTC to ensure that result of Whole blood test is collected on 4th day of submitting sample.

Swaziland Expérience (2010)-Makaria Reynolds et al

50 HIV Infected

Not coming

For ART

Contacted

Active Follow up through Phone Calls

• Phone calls were effective

• Staff invested significant time in calling patients

• Many clients had incorrect information recorded

• Some infants had died

50

ICTC/ARTC Counselor must ensure following:

• Emphasize parent /caregivers the need of prompt follow up for diagnosis and treatment

• Record correct contact information of parent / caregiver

• Contact families for follow-up by phone call and if reqd. home visit, may also take help of ORWs. DSACS will provide travel allowance.

• Record in Register when result was provided to /parent caregiver.

• Add program indicators on % PCR results given to families and percent of PCR positive initiating treatment

51

PMTCT Interventions – Assessing efficacy through EID

Provision of Antiretroviral Drugs

WHO, UNAIDS, UNICEF - Towards Universal Access: Progress Report 2009

55% of pregnant womennot receiving PMTCT drugs

68% of HIV-exposed infantsnot receiving PMTCT drugs

Delhi PMTCT Cascade (2011-12)

Infant feeding Counselling is it really happening ?

MCTC Rates

Overall MCTC rate = 24/234 (10.25%)

But if all DBS Positive Children 53/234 are included in analysis

then MCTC rate = 22.6%The Current PMTCT Intervention is

only 50% effective

New WHO PMTCT Protocol

ARV Prophylaxis and dosing

Antepartum Intra-partum Post-partum

TDF 300mg once daily3TC 150mg twice dailyEFV 600mg once daily

Start at 14 weeks or as soon as possible thereafter

Continue triple ARV prophylaxis

Continue triple ARV prophylaxis until 1 week after all infant exposure to breast milk has ended *

* When the Option-B regimen is stopped, stop EFV and continue with 7-day TDF+ 3TC tail

Maternal Status Intra-partum Post-partum

Presenting in active labour, no prior ARV prophylaxis

sd-NVP 200 mg once at onset of labour withAZT 300 mg + 3TC 150 mg at onset of labour and every 12 hours until delivery

AZT 300 mg + 3TC 150 mg twice daily x 7 days