Review of Early Infant Diagnosis
Programme in Delhi
Presented
By
DR A K Gupta, MD (Pediatrics)
Additional Project Director
Delhi State AIDS Control Society
Govt of Delhi
Agenda items
This presentation will:
•Recapitulate Key concepts in diagnosing HIV infection in
infants and young children
•Explain the National algorithms for diagnosing HIV in infants
and young children
•Explain new strategy to ensure enrollment of all new HIV
exposed for EID
• Inform about Scale up of EID programme during 2012-13
• Explain Adapting WHO (2010) PMTCT protocol
2
Recapitulate Key concepts of EID
Children Continue to Be
Left Behind
Children constitute:
• 10% of new HIV infections each year
o (280,000 out of 2.7 million)
• 6% of the persons living with HIV
o (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
Why early diagnosis is crucial in Infants
?
• Rapid HIV progression and higher risk of death in
infected 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
• CD4 and viral load are poor predictors of disease
progression in infants
Mortality of HIV-infected Infants
1 Year = 35%
mortality
2 Years = 53%
mortality
Newell ML Newell ML et al Lancet 2004; 364:
1236-43
6
Early Initiation of ART Saves Lives
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%.
From the Children with HIV Early Antiretroviral Therapy Study (CHER), Violari, NEJM 2008
7
WHO -new recommendations for starting
ART in infants (2010 revised)
All infants under 24 months of age with
confirmed HIV infection should be started on
antiretroviral therapy, irrespective of clinical or
immunological stage.
What ART to Start in infants –
2010 revision
NVP
triple
ART
No infant or
maternal
ARV exposure
Sd NVP or NNRTI containing ART
MTCT ARV
Exposure
Non NNRTI exposure
Unknown infant
maternal MTCT
Exposure
# If no PI is available use NVP triple ART
http://www.who.int/hiv/paediatric/en/index.html
PI triple
ART#
NVP
triple
ART
NVP
triple
ART
Goals of Early Infant Diagnosis
• 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
10
Methods of Early Infant diagnosis
1. Rapid HIV Antibody Tests
2. RNA PCR
3. DNA PCR
4. Point of Care Tests (P24 assay)
Antibody Detection in 77 HIV-Exposed,
Uninfected Infants in South Africa
100
90
80
70
60
% antibody 50
positive
40
30
20
10
0
Rapid Ab can be used
to exclude infection
around 12-18 months
of age
birth
Moodley D, PIDJ 1995;14:850
1
3
6
9
12
15
18
months of life
12
DNA PCR for Infant Diagnosis
100
90
80
70
60
sensitivity % 50
40
30
20
10
0
At 4-6 weeks of age
sensitivity of
DNA PCR is 9698%
48 hrs
2-7 days
7-14 days
28 days
days
Dunn D, AIDS 1995, 9:F7
13
Limitations of RNA PCR for Infant Diagnosis
DNA PCR assays are preferred for EID over quantitative
RNA PCR because:
(1) DNA assays require whole blood, which is easier to
obtain than the plasma required for RNA assays, and
(2) DNA assays have greater sensitivity than RNA assays if
mothers or infants received antiretroviral drugs for
PMTCT.
However, RNA PCR can be used for viral load monitoring
after established diagnosis.
Point-of-Care Testing for Early Infant
Diagnosis
HIV p24 antigen is produced at high levels within the first few
weeks of infection but quickly becomes bound to specific
antibodies which make it unable to be detected by standard
antigen-detection serological tests.
Heat treatment of the sample dissociates p24 from these
complexes (the ultrasensitive method). It is a sensitive and highly
specific marker for HIV infection Result Time – 1 hour
(Northwestern University)
Limitations- Testing at Multiple sites, Extensive Trainings,
Monitoring, Does Not Eliminate the Need to Improve Lab
Systems, More Stock outs
Process of Enrollling Exposed Infant
for EID
EID Reporting Forms & Registers
•
•
•
•
•
•
•
•
•
•
•
1. Consent Form
2. HIV DNA PCR Test requisition cum Result Form (TRRF Form)
3. HIV DNA PCR Specimen Delivery checklist
4.Exposed Infant/Child Referral form (ICTC-ART/ART to ICTC)
5. ICTC HIV Exposed Infant /child Card
6.DBS Kit Monthly Stock report site level
7.Critical Call out Form for HIV-1 DNA PCR WBS result
8. HIV-1 DNA PCR Monthly specimen receipt and report dispatch log
9. Corrective action log
10. ICTC HIV Exposed Infant/ Child Register
11 ARTC HIV exposed Infant/ Child Register
Dried blood spot (DBS)
a. Whole blood from pricking skin, Dried on filter paper
b. Easy to store & Easy to transport
c. Required supplies for DBS
collection
• Gloves
• Pen
• Lab forms
• DBS card
• Lancet or glucolet
• Disinfectant for skin
• Gauze or cotton wool
Procedure for heel prick 5-10kg infant
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
Warm the area
Wash hands, put on gloves
Position baby with foot down
Clean area, dry 30 sec
Press lancet into foot, prick skin
Wipe away first drop
Allow large drop to collect
Touch blood drop to card
Fill entire circle with drop
Fill at least 3 circles
Clean foot, no bandage
<5kg infants
Overhead 4-5
Fill at least 3 circles
Valid DBS specimen
Overhead 4-34
Invalid DBS specimen:
circles not filled
clotted/layered
Scratched/abraded
Not Dried before sending
Serum Ring around
How to dry DBS
• 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.
HOW TO PACKAGE & TRANSPOPRT DBS
CARD
Insert into sealable plastic bag
Add desiccant packets
(no more than 10 samples per
(minimum 10 packets per bag)
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
NACO Laboratory Guidelines for Diagnosis of HIV in Children < 18
months
1. DBS
a. Sample Collection between 10 AM to 1 PM on every weekday
and packaged and stored at ICTC/PPTCT bewteen 2-8 degree C
b. Transport to Reference Lab NCDC- on 2nd and 4th Tuesday of
the month.
c.NCDC to send report by courier so as to reach site within 7
days of reciept of sample.
2. Whole Blood Collection
a. Sample Collection on 2nd & 4th Tuesday of the calender month
and transport to Ref Lab NCDC on same day, maintain
temperature of 2-25 degree C but do not freeze.
b. NCDC should send report back to ART centre within 4 days of
receipt of sample.
Age at which DNA PCR test is Recommnded by
WHO in HIV Exposed Infants
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.
26
90
80
2005 n=79
76
78
2006 n=108
70
In 2007:
2007 n=109
60
47
50
40
30
30
20
• only 8% of HIV
exposed infants
tested in 1st 2
months of life
• only 4 % started
on co-trimoxazole
23
17
10
0
Number of countries using dired blood
spots for virological testing
Number of countries with a policy on
provider initated testing and counselling for
infants and young children
Towards Universal Access: Scaling up priority HIV/AIDS interventions in the health sector,
WHO/UNAIDS/UNICEF 2008
Missed Opportunties for Early Infant Diagnosis
1. A large no. (40-50%) of HIV exposed infants
never enter EID cascade
2. Missed opportunity for infants born to
mothers with unknown HIV status
Approach to enroll them:
Referring symptomatic infants & children for
early infant diagnosis
Signs & Symptoms of
HIV-Infection in Infants/Children
• Low weight and/or
growth failure
• Pneumonia, including
PCP
• Oral candidiasis
(thrush) after 6 weeks
of age
•
•
•
•
•
Lymphadenopathy
Parotid gland swelling
Recurrent ear infections
Persistent diarrhoea
Tuberculosis
Exclusive Breastfeeding
• 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
Risks Associated with Mixed Feeding
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
Exclusive Breastfeeding:
Early Cessation
• 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
Cotrimoxazole Preventive Therapy
• 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.
36
Cotrimoxazole Prophylactic Therapy
• The CPT should be given from 6 weeks onwards to the weight of the
infant/Child.
Weight( Kg)
Child dispersible tablets( 20mg
TMP/100mg smx) X Once daily
<5
5-10
1 tablet
2 tablet
10-15
15-22
3 tablet
4 tablet
• 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
Cotrimoxazole Prophylaxis
• 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 children
• If a child develops severe reaction to CTX
Dapsone can be used for prophylaxis
(2mg/kg/dose daily, maximum 100mg daily)
38
Reviw of Performance of EID programme
during 2011-12
 What
proportion of pregnant women testing HIV+ get their HIVexposed 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?
Why PI Containing ART Regimen for Nevirapine (NNRTI)
Exposed HIV Infected Children?
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
1. Diagnostic testing at 4 to 6 weeks of age for all HIV‐exposed
infants, with quick turnaround of test results for immediate
initiation if needed.
2. Universal treatment with ART for all infants and children
under 2 years of age, regardless of CD4 count or clinical stage
with 2 NRTI + 1 NNRTI
3. Infants who have been exposed to maternal or infant NVP or
other NNRTIs should be started on protease inhibitors (PIs).
Issues and Challenges
• 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 i.e by 12 weeks of age
Other issues
1. Adherence to CPT ?
2. Infant Feeding Counseling ?
Supply Chain Management has not been a
problem in Delhi
Scale up of EID programme during 2012-13
Existing DBS collection facility in Delhi
S. No.
Designated DBS collection sites
1.
LNJP (PPTCT)
2.
Dr. Hedge war Hospital (PPTCT)
3.
Sucheta Kriplani Hospital (PPTCT)
4.
Mrs. GLM Hospital (PPTCT)
5.
Hindu Rao Hospital (PPTCT)
6.
DAD Dispensary, Ashok Vihar
7.
Kasturba Hospital (PPTCT)
8.
GTB Hospital (PPTCT)
9.
SDN Hospital (PPTCT)
S. No.
Designated DBS collection sites
10.
Dr. B.S.A. Hospital (PPTCT)
11.
BJRM Hospital
12.
Maharishi Balmiki Hospital
13.
AIIMS (PPTCT)
14.
NDMC, Palika Maternity Home
15.
Safdarjung Hospital(PPTCT)
16.
RTRM Hospital (PPTCT)
17.
GGS Hospital(PPTCT)
18.
ASB Hospital
19.
DDU Hospital (PPTCT)
New DBS Collection Facilities
S. No.
DBS collection sites
Unique DNA Infant code
First 10 digits of code
Year
S. No. at
ICTC
001
onwards
1.
LBS Hospital (PPTCT)
DNADLEAS02
12
001
2.
RML Hospital(PPTCT)
DNADLNEW03
12
001
3.
Bhagwan Mahaveer Hospital
DNADLNWS04
12
001
4.
Sanjay Gandhi Memorial Hospital
DNADLNWS05
12
001
5.
Satyavadi Raja Harischandra Hospital
DNADLNWS06
12
001
6.
Pt. Madan Mohan Malviya Hospital
DNADLSOU04
12
001
7.
Dada Dev Matrey Avum Shishu Chikitsalaya
DNADLSWS02
12
001
8.
National center for Disease Control
DNADL NOR04
12
001
Strategy
to Address the issues
Ensuring Adherence to CPT
1. ICTC/PPTCT Counselor should conduct proper counsleing of
mother at the time of starting CPT at 6 weeks of age. ART
Counselor should also check for adherence to CPT.
2.Monitor for CPT adherence - DBS Negative infants by ICTC
Counselor and WB PCR reactive infants initaited ART by ART
Counselor
3.Provide stock sufficient till the next imunization visit (10
weeks, 14 weeks). After 14 weeks provide CPT for 2 months
and call mother every 2 months to receive supply. Inform
mother when CPT will be discontinued.
Infant feeding Counselling- is it really happening ?
Infant feeding counseling should be done at 3 crtitical
steps:
a. Within 24 hours of birth of HIV exposed baby
b. At 6 weeks of age at the time of EID
c. At about 6 months of age (weaning in BF infants)
Day 1-3 : Ensure first DBS DNA PCR
test at 6 weeks of age & Send
sample to NCDC within 2 days
(ICTC/PPTCT)
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.
Day 31/32: ART Centre call parents
to start ART in confirmed HIV +ve
infants within 7 days ie < =12
weeks of age
Improving Follow-up
Swaziland Expérience (2010)-Makaria Reynolds et al
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
8 Died
50 HIV
Infected
Not
coming
For
ART
12 LTFU
Contacted
4 Refused
26 Initiated
ART
52
Getting Results to Families
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
53
New WHO PMTCT Protocol
PPTCT Option-B, triple ARV prophylaxis for women
ARV Prophylaxis
and dosing
Antepartum
Intra-partum Post-partum
TDF 300mg once
daily
3TC 150mg twice
daily
EFV 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
ARV prophylaxis for pregnant women presenting in active labour with no
prior ARV prophylaxis
Maternal Status
Intra-partum
Post-partum
Presenting in
active labour, no
prior ARV
prophylaxis
sd-NVP 200 mg once AZT 300 mg + 3TC 150 mg
twice daily x 7 days
at onset of labour
with
AZT 300 mg + 3TC
150 mg at onset of
labour and every 12
hours until delivery
Protocol PPTCT-3: ARV prophylaxis for women presenting directly in labour