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