review of early infant diagnosis of hiv-1 in delhi by dr.a.k. gupta, additional project director cum...
DESCRIPTION
This presentation describes efficacy of early Infant diagnosis of HIV-1 in assessment of effectiveness of various PMTCT interventions. There is an urgent need to reduce large number of unnecessary Cesarean Sections on HIV positive pregnant women.TRANSCRIPT
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