1. Infant clinical considerations
IMPAACT 2010 study-specific Training
May 2017

2. Overview Medical, Medication, and Feeding Histories
Physical Examinations
Laboratory Evaluations
Source Documentation and eCRF Requirements

3. Overall Approach to Infant Management
Infants enrolled in this study should receive ARV prophylaxis and other standard interventions such as cotrimoxazole, isoniazid preventive therapy, and childhood immunizations consistent with local standards of care from non-study sources. Likewise, infants diagnosed with HIV infection should receive ART consistent with local standards of care from non-study sources.

4. Overall Approach to Infant Management
In the event that mothers need to interrupt ART (e.g., due to an adverse event), information and counseling will be provided regarding locally- available options for reducing the risk of perinatal HIV transmission. Such options may include infant ARV prophylaxis during breastfeeding and replacement feeding if determined to be safe and accessible and if the mother’s ART interruption is likely to be prolonged.

5. Infant Medical and Medication History
Required at each scheduled visit
Baseline history at Delivery Visit
Interval (since the last visit) histories at subsequent visits

6. Infant Medical and Medication History
Birth details should ideally be obtained from medical records
Thereafter, history information may be obtained based on maternal report but available medical records should also be obtained when possible to supplement maternal report

7. Infant Baseline History
Assess for and
Source Document
Enter into eCRFs
Date and time of birth
Yes
Sex, estimated gestational age, length, weight, and head circumference at birth
Apgar scores at 1 and 5 minutes
On my computer, the whiter font on the green background is very hard to read – maybe could use a slightly darker green?

8. Infant Baseline History
Assess for and
Source Document
Enter into eCRFs
Congenital anomalies and other medical conditions (signs, symptoms, illnesses, other diagnoses) identified between birth and the Delivery Visit
Any conditions
(adverse events)
that meet criteria in protocol Section 7.2
including all suspected
congenital anomalies

9. Infant Baseline History
Assess for and
Source Document
Enter into eCRFs
Medications taken between birth and the Delivery Visit
All ARVs
Any use of:
Cotrimoxazole
Isoniazid prophylaxis
Medications to treat active TB
All medications taken at onset of or in response to adverse events that are specified to be entered into eCRFs per Section 7.2
Note: eCRFs will also capture whether traditional medications were taken during follow-up.

10. Infant Interval History
Assess for and
Source Document
Enter into eCRFs
Current status of conditions that were ongoing at the
previous visit
Any updates of
previous entries
(e.g., resolution dates)
Occurrence of any new conditions (signs, symptoms, illnesses, and other diagnoses) since the last visit
Any newly identified adverse events
that meet criteria in protocol Section 7.2

11. Infant Interval History
Assess for and
Source Document
Enter into eCRFs
Current status of medications that were ongoing at the last visit
Any updates of
previous entries
(e.g., stop dates)

12. Infant Interval History
Assess for and
Source Document
Enter into eCRFs
Use of any new medications
since the last visit
All ARVs
Any use of:
Cotrimoxazole
Isoniazid prophylaxis
Medications to treat active TB
All medications taken at onset of or in response to adverse events that are specified to be entered into eCRFs per Section 7.2
Note: eCRFs will also capture whether traditional medications were taken during follow-up.

13. Infant Feeding History
Required at each scheduled visit
At Delivery Visit: feeding history since birth
At subsequent scheduled visits: interval (since the last visit) feeding history

14. Infant Feeding History
At this visit, was the infant's feeding method assessed?
Since the last visit, has there been a change in the infant's feeding method?

15. QLW10010: Infant Feeding Method QLW10011: Breastfeeding, Formula, &
QLW10010: Infant Feeding Method QLW10011: Breastfeeding, Formula, & Complementary Food Record
Has infant been breastfed?
Breastfed by mother or someone else?
Date and time of first breastfeeding
Date of last exposure to breast milk
Has infant been formula fed?
Date of first formula feeding
Has infant received complementary foods?
Date of first complementary food

16. Complete Infant Physical Exam
Covered on Day 2 of training as part of Delivery Visit session

17. Targeted Infant Physical Exam
Length
Weight
Head circumference
Fontanel closure
Examination of body systems driven by prior and new signs, symptoms, and diagnoses
At all visits, additional assessments may be performed
at the discretion of the examining clinician

18. Infant Growth Monitoring
Study clinicians are responsible for monitoring infant growth throughout follow-up
At all visits, current measurements should be charted and compared to measurements recorded at the last visit to assess for appropriate increases
At all visits, weight-for-length should be assessed in relation to WHO growth standards

19. DAIDS Grading Table Version 2.1
should be
weight-for-length z score

20. Infant Laboratory Evaluations
Complete blood count, ALT, creatinine
Delivery Visit for all infants
Week 26 Visit if currently breastfeeding
Additionally if clinically indicated

21. Recording Test Results on Laboratory eCRFs
All creatinine results
All Grade 2 or higher ALT results
All grade 3 or higher hemoglobin, WBC, ANC, and platelet count results
All results that are serious as defined in the DAIDS EAE Manual
*Regardless of whether test was protocol-specified or ordered for clinical purposes

22. Infant Evaluations Adverse Events Exams History Lab Tests
I like this slide!

23. Recording on Adverse Event eCRFs
All Grade 3 or higher adverse events
All suspected congenital anomalies
All SAEs as defined in the DAIDS EAE Manual

24. Enter Adverse Event eCRF?
A few examples
Event
Enter Value
in Lab eCRF?
Enter Adverse Event eCRF?
Grade 1 creatinine
Yes No
Grade 2 creatinine
Grade 3 creatinine
Yes*
Grade 4 creatinine

25. Enter Adverse Event eCRF?
A few examples
Event
Enter Value
in Lab eCRF?
Enter Adverse Event eCRF?
Grade 1 creatinine
Yes No
Grade 2 creatinine
Grade 3 creatinine
Yes*
Grade 4 creatinine
*AE term = increased creatinine

26. Enter Adverse Event eCRF?
A few examples
Event
Enter Value
in Lab eCRF?
Enter Adverse Event eCRF?
Grade 1 hemoglobin No
Grade 2 hemoglobin
Grade 3 hemoglobin
Yes
Yes*
Grade 4 hemoglobin

27. Enter Adverse Event eCRF?
A few examples
Event
Enter Value
in Lab eCRF?
Enter Adverse Event eCRF?
Grade 1 hemoglobin No
Grade 2 hemoglobin
Grade 3 hemoglobin
Yes
Yes*
Grade 4 hemoglobin
*AE term = decreased hemoglobin
or anemia if symptomatic

28. Adverse Event Management
All adverse events must be source documented in participant research records, including the severity of each event and its relationship to study drug (infant exposure in utero or through breastfeeding)
All adverse events must be followed to resolution (return to baseline) or stabilization, with the frequency of repeat evaluations determined by the clinical significance of each event
Grade 3 or higher laboratory tests should be repeated as soon as possible (within three business days) and all grade 3 or higher adverse events should be re-evaluated at least weekly until improvement to grade 2 or lower
Protocol Section 8.1

29. Adverse Event Management
Infant adverse events will be managed consistent with the best medical judgment of the site investigator and local clinical practice standards
It is not expected that maternal study drug regimens will routinely be modified in response to infant adverse events; site investigators may modify use of infant ARVs and other concomitant medications in response to infant adverse events
Protocol Section 8.1

30. Adverse Event Management
Consultation with the CMC is available but not required for most infant adverse events
Should an infant experience a grade 3 or higher adverse event assessed as related the mother’s current study drug regimen, the CMC should be consulted
Protocol Section 8.1

31. Infant Laboratory Evaluations
HIV Nucleic Acid Test (NAT)
Delivery, Week 6, and Week 14 Visits for all infants
Week 26 and Week 38 Visits if any exposure to breast milk since the last NAT (“if BF”)
Week 50 Visit for all infants

32. Infant HIV Infection
Any infant with a positive HIV NAT result should be recalled for confirmatory testing as soon as possible and within 28 days of specimen collection for the initial test
3 mL of blood should be collected for the testing and residual plasma should be stored
If the second test does not confirm the initial result, the CMC should be consulted for guidance on next steps to clarify the infant’s HIV status
Pending confirmatory testing, infant prophylaxis should be managed consistent with local standards of care
Section 6.8

33. Infant HIV Infection
All infants identified with HIV infection will remain in study follow-up but will be referred to non-study sources of HIV care and treatment as soon as possible
Study visits will be conducted as originally scheduled with the exception that no further HIV tests will be performed and stored plasma will be used for antiretroviral resistance testing
Study sites may perform additional laboratory testing as needed to facilitate rapid initiation of ART for infected infants
Section 6.8
Should we add something about the required post-study contact if the infant’s HIV NAT comes back positive at the Week 50 visit? I was thinking about adding something for the maternal virologic failure in the postpartum scenarios time and could add something about subsequent pregnancies into that section as well?

34. What are your questions?