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How to increase testing in children?. Dr Jennifer Cohn Medical Coordinator Médecins Sans Frontières , Access Campaign 7th International AIDS Conference 2 July 2013. ART coverage for infected children remains low. Source : WHO 2013. 63 0,000 children on treatment end 2012
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How to increase testing in children? Dr Jennifer Cohn Medical Coordinator Médecins Sans Frontières, 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 Task shifting 2013 WHO Consolidated HIV Guidelines 2013 WHO Consolidated HIV Guidelines
Time is of the Essence • Importance of Timing • Intra-uterine/perinatal transmission: mortality peaks at 8-12 weeks of ageand 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.
4 Emerging concerns • 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
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 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 The timing with the EPI is not strictly necessary but will be useful where both services are decentralised and can be linked. • 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) POC Positive Initiate ART asap Negative Second virological test at 10 weeks (EPI: OPV2, Pentavalent2, PCV2, Rotavirus2) Virological assays: as above POC Confirm result on new specimen preferably collected before ART initiation, or as soon as possible, without delaying ART initiation Virological assays: as above Negative HIV infection ruled out Continue monitoring if infant/child is still breast-feeding until at least 6 weeks post-cessation Negative Discrepant result Confirm result on new specimen Preferably use HIV TNA real time RT-PCR First serological test at 9 months (EPI: measles) Positive HIV infection confirmed Continue ART Negative HIV infection ruled out Continue monitoring if infant/child is still breast-feeding until at least 6 weeks post-cessation Positive HIV exposure confirmed Confirm infection with a virological test Infants should be tested at any time that they develop symptoms consistent with HIV. 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 adults WARNING: 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. PCR results should be returned to the clinic and mother-baby pair, and an intervention initiated, within 1 month of the sample being taken.
HIV DNA test sample collection and delivery of result by m-health can be challenging – example rural Malawi Oh my Jesus Christ! This is the 2nd time I come here! If the rider goes daily to TDHL, why does he not take DBS strips with him? We've been more than one month without DBS-kits! I have not been trained on DBS/STS!!! Stock ruptures Capacity of HSAs My colleagues are in the field and I'm struggling here!!! I cannot send the mother to the next clinic because they don't have kits either!! Does anybody at TDH Lab care at all about this??? Maybe I should rather go to the traditional healer? I am not aware of DoH/TDHL mentoring DBS services! DBS sampling Data management I had to walk 10 km back home only because I forgot that damn Health Passport! Gloves protect me... I don't need to wash my hands. I cannot understand why in TDHL and QECHL complain that they have too much data to encode! The worst is on me! This is the 2nd time they've changed this Logbook... We don't have soap here anyway! I wish somebody could come here and tell me if I'm doing it right! Data is not being filled in! And I also have to fill in the Health Passport, the Pink Card, the delivery checklist... There is no need to lock this room... Who's goning to want to steal these papers?
We have to use whatever we can to transport samples to QECH The rider arrives at the clinic the day I'm collecting more samples I hate the new DBS papers. The blood slides out of the circle and the circles cannot be punched out! This sample is OK Sample transport Samples rejected Anyway I'm tired and I do not want to repeat the sample, I never receive any feedback from the Lab... Samples can be sitting for up to one month in TDH Lab! And sometimes the rider does not find an HSA to check if he is doing everything as he should ... And many mothers do not care to come for their results. And the drivers taking the samples to QECH leave them at any place! SMS to phone sites SMS printers They say it is a mess... UNICEF, CHAI, MSF, MoH... Who is responsible for this? I wonder why MSF took our printer away... I'm at home now cooking my nsima. I'll retrieve the SMS and hope I'll not forget to register it later... I'm going to be moved to a different health site... How can I get results from the new site? Printers were not working since October at least... ...and when I pressed the Please Call Me button nobody assisted us Why does TDH have a printer and we do not? TDH is the 1st place where results arrive... 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'd prefer to get the results on my phone. Acknowledgement: Guillermo “m-health” Martínez, MSF Malawi
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 Epidemiol2011 • Dubeet al. Bull WHO 2012 • Kagehaet al. J Trop Pediatr 2012 • Feuchtet al. SAMJ 2012 • Lilianet al. J Clin Micro 2012 • Burgard et al. J Pedriatr2012 • Garcia-Prats et al. AIDS 2012 • Kfutwahet al. J Acquir Immune DeficSyndr2011 • Hainaut et al. CID 2005