1. Maternal Toxicity Management
IMPAACT 2010/VESTED
Section 8 and Appendix II

2. Overall Guidelines Page 80
IMPAACT 2010 will use the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.1, dated March 2017, with two modifications:
Protocol-specific grading for axillary measured fever
Grade 1, 37.4 to <38.0°C
Grade 2, 38.0 to <38.7°C
Grade 3, 38.7 to <39.4°C
Grade 4, ≥39.4°C
The DAIDS AE Grading Table parameter for weight loss excludes postpartum weight loss. Therefore, maternal weight loss will not be graded in this study.
Will be updated
Anne – should we say something here about potential updates to the note in this section?
“Note: The DAIDS AE Grading Table parameter for weight loss excludes postpartum weight loss. Therefore, maternal weight loss not be graded in this study.”
In the draft CM, we added “unintentional” weight loss 2

3. Page 81
General Guidelines
All maternal and infant AEs identified in the study will be source documented in participant research records, including:
Severity of each event
Relationship to study drug 3

4. Page 81
General Guidelines
All AEs must be followed through resolution (return to baseline) or stabilization
Frequency of repeat evaluations determined by the clinical significance of each event
Grade 3 or higher AEs should be repeated as soon as possible (within 3 business days) and re-evaluated weekly
Additional evaluations may be performed as the site investigator’s discretion 4

5. Communication
IMPAACT 2010 Clinical Management Committee (CMC) will address site management questions
When management requires consultation, contact the CMC as soon as possible and within 3 business days of site awareness of the event

6. Management of Maternal Adverse Events
Management Category
Appendix Table
General Guidelines for Maternal Toxicity Management
Table II.1
Rash
Table II.2
Asymptomatic ALT or AST elevation
Table II.3
Clinical hepatitis
Table II.4
Increased creatinine and decreased creatinine clearance
Table II.5
Psychiatric events
Table II.6
Allergic reaction
Table II.7
Switching from TDF or TAF to ZDV or ABC
Table II.8
nc = no change 6

7. Additional Maternal Management Guidelines
Maternal HIV viral load
Mothers who develop active tuberculosis
Mothers who are co-infected with hepatitis B
Contraception and management of mothers who become pregnant on study
Maternal nervous system and psychiatric symptoms
Immune reconstitution syndrome
Discussed earlier 
We will not go through each of the sections in detail but will point out some notes related to these management considerations 7

8. Additional Maternal Management Guidelines
Maternal HIV viral load
Mothers who develop active tuberculosis
Mothers who are co-infected with hepatitis B
Contraception and management of mothers who become pregnant on study
Maternal nervous system and psychiatric symptoms
Immune reconstitution syndrome 8

9. Active Tuberculosis
Mothers who develop active TB may need rifampin-containing treatment
These mothers may have their study drug regimen modified consistent with package inserts
Increase frequency of DTG dosing from 50 mg once daily to 50 mg twice daily
TAF should be switched to TDF

10. Active Tuberculosis
Contact the CMC for each TB diagnosis AND to consult on study drug regimen management
Conduct an additional study visit (Post-ARV Switch Visit) about 4 weeks after the switch for any mother whose study drug regimen is modified such that DTG or EFV is replaced with another ARV

11. Additional Maternal Management Guidelines
Maternal HIV viral load
Mothers who develop active tuberculosis
Mothers who are co-infected with hepatitis B
Contraception and management of mothers who become pregnant on study
Maternal nervous system and psychiatric symptoms
Immune reconstitution syndrome 11

12. Hepatitis B
Hepatitis B surface antigen testing is conducted for all women at study entry
Mothers who are HepB+ who initiate or discontinue ARVs that are active against Hep B may be at risk of immune reconstitution or rebound hepatitis viremia
Monitor closely for symptoms of hepatitis
Contact the CMC for any mother who has symptoms of hepatitis

13. Hepatitis B
For infants exposed to hepatitis B, every effort should be made to facilitate access to the best available local standard management for hepatitis B exposure, including the hepatitis B vaccine series, starting at birth
Further management in provided in protocol Appendix II, Tables II.3 and II.4

14. Additional Maternal Management Guidelines
Maternal HIV viral load
Mothers who develop active tuberculosis
Mothers who are co-infected with hepatitis B
Contraception and management of mothers who become pregnant on study
Maternal nervous system and psychiatric symptoms
Immune reconstitution syndrome 14

15. Contraception counseling
Will be done per local standards of care
Discussed earlier 

16. Mothers who become pregnant on study
Maintain in follow-up
May remain on current study drug regimen but should be provided information and counseled on their current regimen
Mothers who choose to receive study drug during a subsequent pregnancy must provide separate informed consent.

17. Additional Maternal Management Guidelines
Maternal HIV viral load
Mothers who develop active tuberculosis
Mothers who are co-infected with hepatitis B
Contraception and management of mothers who become pregnant on study
Maternal nervous system and psychiatric symptoms
Immune reconstitution syndrome 17

18. Nervous System and Psychiatric Symptoms
EFV and DTG may have nervous system symptoms
Mothers will be assessed for postpartum depression, sleeping patterns, and anxiety
Discussed earlier 
Discussed earlier 
Further management in provided in protocol Appendix II, Tables II.1 and II.6.

19. Additional Maternal Management Guidelines
Maternal HIV viral load
Mothers who develop active tuberculosis
Mothers who are co-infected with hepatitis B
Contraception and management of mothers who become pregnant on study
Maternal nervous system and psychiatric symptoms
Immune reconstitution syndrome 19

20. Immune Reconstitution Inflammatory Syndrome
AEs assessed as secondary to immune reconstitution should not be considered related to study drug
Contact the CMC for any mother who has suspected IRIS 20

21. What are your questions?