how to increase testing in children? dr jennifer cohn medical coordinator médecins sans...
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How to increase testing in children?
Dr Jennifer CohnMedical Coordinator
Medecins Sans Frontieres, Access Campaign
7th International AIDS Conference 2 July 2013
ART coverage for infected children remains low
Source : WHO 2013
• 630,000 children on treatment end 2012
• 39% coverage of need• Only 11% increase vs 2011
Active case finding and early identification of HIV exposed children is critically important
• Identify HIV children : – At birth (6 weeks)– At end of breast-feeding– Later - symptomatic
• Identify (newly) infected mothers and siblings
EID Cascade
Optimize PMTCT
Timely EID and monitor
Sample collection & processing
Results transmission Initiation GLs Appropriate
RxManageable formulation
2013 WHO Consolidated HIV Guidelines
2013 WHO Consolidated HIV Guidelines
Task shifting
• Importance of Timing– Intra-uterine/perinatal transmission: mortality peaks at 8-12 weeks of age and higher
mortality– South African study:
• Prospective cohort 848 mom-baby pairs with EID at birth versus 6 weeks using 3 assays: Amplicor HIV-1 DNA PCR (Roche), CAP/CTM RT-PCR (Roche) and Aptima HIV-1 Assay (Gen-Probe).
• At birth, the CAP/CTM and Aptima assays diagnosed 76.3% (n=29) of all infants positive by 6 weeks (n=38) and were more sensitive than the Amplicor assay (n=26; 68.4%)
• Only 68% of IU/IP infected presented for 6 week f/u• Before ART could be started 45% of IU and 22% of IP infected infants LTFU or dead
• Advantages of the at birth EID include:– Reduce LTFU in facilities and for those giving birth at home, this could be linked to the BCG
vaccination visit.– Identifying additional infections at birth than would not otherwise have been detected at 6
weeks. This is due to the possibility that daily prophylaxis may suppress viral replication and delay
the diagnosis of EID beyond 6 weeks. This requires further investigation.
Time is of the Essence
• The currently used virological tests may not be as sensitive in the context of ARV exposure as part of PMTCT prophylaxis– RNA tests may be more sensitive – measure TNA as will also pick up DNA
• The risk of false negative serological and virological results in infants aged ≥18 months who have been initiated on ART on the basis of a presumptive diagnosis but still require a confirmation of infection– More seroreversion for those initiated <9 mo– In cases where a false negative result is possible, additional testing to evaluate for a false
negative result (e.g. ELISA instead of RDT; virological test on a microtube of whole blood rather than a DBS) before the infant is taken off of ART.
– Importance of scaling out EID to eliminate need for empiric Rx• Reinforce confirmatory testing – for NA testing and no need for serology if NA
positive• The greater use of maternal ART and longer duration of infant prophylaxis may
require a revision of the timing of EID testing in order to maximize sensitivity and allow for initiation of ART prior to the peak of infant mortality
4 Emerging concerns
Time to DNA-PCR positivity in non- breastfed infants (non-B HIV subtype) may be later with receipt of ≥3
ARVs than with other ARV categories • Individual subject data for non-breastfed, HIV-infected infants in cohorts in Thailand, South Africa, Botswana, and the
United Kingdom (African origin)• WHO recommended EID time-point = 4-6 weeks (30-42 days) • TABLE: Cumulative Probability of Testing Positive
Combined Maternal/Infant ARV Category
No. of Infants (Total no. of Tests)
Birth - 1 Day of Age
≤14 Days of Age
≤30 Days of Age
≤42 Days of Age
≤90 Days of Age
≤370 Days of Age
No ARV to Mother or Infant 125 (n=357)
0.31 (n=63)
0.94 (n=95)
0.94 (n=108)
0.94 (n=119)
1.0 (n=228)
1.0 (n=357)
Single NRTI to Mother or Infant (or both)
159 (n=573)
0.63 (n=127)
0.63 (n=149)
0.91 (n=161)
0.91 (n=188)
0.96 (n=315)
1.0 (n=573)
Single-dose NVP +/- single NRTI (sdNVP) to Mother or Infant (or both)
105 (n=351)
0.71 (n=42)
0.82 (n=86)
0.82 (n=96)
0.96 (n=148)
1.0 (n=223)
1.0 (n=351)
≥3 ARVs to Mother or Infant (or both)
43 (n=122)
0.67 (n=24)
0.67 (n=42)
0.67 (n=55)
0.79 (n=65)
0.94 (n=86)
1.0 (n=122)
Shapiro et al. IAS 2013 Abstract no. TUAB0203
EID: Suggested new algorithm (to form the basis of discussion with experts)Exposed infant enrolled in PMTCT program
First virological test at or within one week of birth(at birth, post-natal visit or EPI: BCG)Virological assays:-HIV DNA PCR on whole blood (microtube or DBS)-HIV RNA (or TNA) real time RT-PCR on plasma or whole blood (microtube or DBS) (PREFERRED)-Other nucleic acid amplification test (e.g. isothermic e.g. NASBA)-Us p24 Ag on plasma or whole blood (microtube or DBS)
PositiveInitiate ART asap
NegativeSecond virological test at 10 weeks(EPI: OPV2, Pentavalent2, PCV2, Rotavirus2)Virological assays: as aboveConfirm result on new specimen
preferably collected before ART initiation, or as soon as possible, without delaying ART initiation Virological assays: as above
PositiveHIV infection confirmedContinue ART
NegativeDiscrepant resultConfirm result on new specimenPreferably use HIV TNA real time RT-PCR
NegativeHIV infection ruled outContinue monitoring if infant/child is still breast-feeding until at least 6 weeks post-cessation
PCR results should be returned to the clinic and mother-baby pair, and an intervention initiated, within 1 month of the sample being taken.
First serological test at 9 months(EPI: measles)
PositiveHIV exposure confirmedConfirm infection with a virological test
NegativeHIV infection ruled outContinue monitoring if infant/child is still breast-feeding until at least 6 weeks post-cessation
If HIV infection status has not been confirmed: second serological test at 18 months(EPI: DPI booster, OPV booster)Serological testing algorithm ≥18 months as for adultsWARNING: If infants have been treated empirically then false negative serological and virological tests are possible. Perform, preferably more sensitive, confirmatory tests before taking a child off ART and consult a paediatric HIV specialist.
The timing with the EPI is not strictly necessary but will be useful where both services are decentralised and can be linked.
POC
POC
Infants should be tested at any time that they develop symptoms consistent with HIV.
HIV DNA test sample collection and delivery of result by m-health can be challenging – example rural Malawi
Capacity of HSAsI have not been
trained on DBS/STS!!!
I am not aware of DoH/TDHL
mentoring DBS services!
My colleagues are in the field
and I'm struggling
here!!!
Oh my Jesus
Christ! This is the 2nd time I come here!
Maybe I should
rather go to the
traditional
healer?
We've been more
than one month
without DBS-kits!
I cannot send the
mother to the next
clinic because
they don't have kits either!!
If the rider goes daily to TDHL, why
does he not take DBS
strips with him?
Does anybody at TDH
Lab care at all about
this???
Gloves protect me... I don't need
to wash my hands.
We don't have soap here anyway! I wish
somebody could come here and tell
me if I'm doing it right!
There is no need to lock this room... Who's goning to want to
steal these papers?
I had to walk 10 km back home only because I
forgot that damn Health
Passport!
DBS sampling
Stock ruptures
Data management
This is the 2nd time they've changed this
Logbook...
And I also have to fill in the Health Passport, the Pink
Card, the delivery checklist...
I cannot understand why in
TDHL and QECHL
complain that they have too
much data to encode! The worst is on me!
Data is not being filled in!
Acknowledgement: Guillermo “m-health” Martínez, MSF Malawi
Sample transportWe have to use
whatever we can to
transport samples to
QECH
The rider arrives at the clinic
the day I'm collecting
more samples
And sometimes
the rider does not
find an HSA to check if he is doing everything
as he should
Samples can be sitting for up to one month in
TDH Lab!
And the drivers taking the samples to QECH
leave them at any place!
Samples rejectedI hate the new DBS papers.
The blood slides out
of the circle and the circles cannot be punched
out!
This sample is OK
Anyway I'm tired and I do not want to repeat the sample, I
never receive any feedback
from the Lab...
... And many mothers do not care to come for their results.
SMS printersI wonder why MSF
took our printer away...
Printers were not working since October at least... ...and when I pressed the Please Call
Me button nobody assisted us
They say it is a mess... UNICEF,
CHAI, MSF, MoH... Who is
responsible for this?
Why does TDH have a printer and we do not? TDH is
the 1st place where results
arrive...I'd prefer to get the results on my phone.
SMS to phone sitesI'm at home now
cooking my nsima. I'll retrieve the SMS and hope I'll not forget to
register it later...
Oh! My inbox is full, I better delete this
SMS...Isn't it great? I haven't
received an SMS for a while because we were not doing
DBS... But I'm still getting my 300 Kwacha!
I'm going to be moved to a different health site...
How can I get results from the new site?
Conclusions and Recommendations
• Despite major progress in PMTCT, HIV-infected children will remain a reality for the next decade
• EID is neglected and needs prioritisation need to diagnose infants early and accurately to take advantage of new WHO treatment recommendations
• Revision of guidelines to include birth EID as well as POC diagnostics and streamlined initiation criteria may help plug leaky cascade
• New tools: DBS, POC, scale out of general VL monitoring=opportunity!
• Infrastructure problems must also be addressed
References
• Bourne et al. AIDS 2009• Marston et al. Int J Epidemiol 2011• Dube et al. Bull WHO 2012• Kageha et al. J Trop Pediatr 2012• Feucht et al. SAMJ 2012• Lilian et al. J Clin Micro 2012• Burgard et al. J Pedriatr 2012• Garcia-Prats et al. AIDS 2012 • Kfutwah et al. J Acquir Immune Defic Syndr 2011• Hainaut et al. CID 2005
THANK YOU