Maternal clinical considerations

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

2. 2 Overview • Medical and Medication Histories • Standardized Questionnaires (role play) • Physical Examinations • Laboratory Evaluations • Source Documentation and eCRF Requirements

3. Maternal Medical and Medication History • Required at each scheduled visit • Baseline history at Screening and Entry • Establishes condition at study entry for comparison with condition during follow-up • Interval (since the last visit) histories at subsequent visits

4. Maternal Medical and Medication History • All history information may be obtained based on maternal self-report but available medical records should be obtained when possible to supplement self-reported information

5. Maternal Baseline History

6. Maternal Baseline History

7. Complete at Entry Visit to record all conditions diagnosed in the index pregnancy before Entry

8. Maternal Baseline History

9. Maternal Baseline History

10. Maternal Interval History

11. Maternal Interval History

12. Maternal Interval History • Record DTG, FTC/TAF, FTC/TDF, EFV/FTC/TDF taken after enrollment on Treatment Log (TXW10001) • Record all other ARVs taken after enrollment on Con Meds Log (CMW10001)

13. Maternal Interval History

14. Additional History at Delivery Visit • Complications of pregnancy identified following enrollment • Other targeted conditions potentially associated with adverse pregnancy outcomes identified following enrollment • Date and time of onset of labor • Type of labor (spontaneous or induced) • Mode of delivery • Complications of delivery • Outcome of delivery • Corticosteroids taken for fetal lung maturity at any time during pregnancy

15. Complete at Delivery to record all conditions diagnosed in the index pregnancy after Entry

16. Forthcoming in the MOP • Mapping of protocol-specified history elements to eCRFs

17. What are your questions about maternal histories?

18. StandardizedQuestionnaires • QLW10000: IMPAACT 2010 Edinburgh Postnatal Depression Scale (Week 6 postpartum, Week 50 postpartum) • QLW10005: IMPAACT 2010 Pittsburgh Sleep Quality Index Questionnaire (Entry, Week 8 antepartum, Week 38 postpartum) • QLW10006: IMPAACT 2010 Generalized Anxiety Disorder 7-Item Scale (Entry, Week 8 antepartum, Week 38 postpartum)

19. Role Play

20. StandardizedQuestionnaires • Who will administer each questionnaire? • After the questionnaire is completed, who will evaluate responses with respect to needs for further evaluation, treatment, documentation, and/or reporting of reported symptoms? • Who will determine ARV management?

21. StandardizedQuestionnaires

22. Mental HealthManagement Guidelines Table II.6, Management of Maternal Psychiatric Events (Insomnia, Psychiatric Disorders, Suicidal Ideation or Attempt)

23. Table II.6, Management of Maternal Psychiatric Events (Insomnia, Psychiatric Disorders, Suicidal Ideation or Attempt)

24. Table II.6, Management of Maternal Psychiatric Events (Insomnia, Psychiatric Disorders, Suicidal Ideation or Attempt)

25. Table II.6, Management of Maternal Psychiatric Events (Insomnia, Psychiatric Disorders, Suicidal Ideation or Attempt)

26. What are your questions about maternal questionnaires?

27. Complete Maternal Physical Exam • Height (screening) • Weight • Blood pressure • Auscultation of chest • Obstetric exam (antepartum) • Examination of • Skin • Head • Mouth • Neck • Abdomen • Extremities additional assessments may be performed at the discretion of the examining clinician

28. Targeted Maternal Physical Exam • Weight • Blood pressure • Obstetric exam (antepartum) • Examination of body systems driven by prior and new signs, symptoms, and diagnoses additional assessments may be performed at the discretion of the examining clinician

29. MaternalLaboratory Evaluations • HIV-1 RNA • Entry • Weeks 4, 8, 12, 24 antepartum • Delivery • Weeks 14, 26, 38, 50 postpartum • Confirmation of Virologic Failure • Post ARV Switch

30. MaternalVirologic Monitoring • Refer to protocol Sections 6.7 and 8.3 • Closely monitor trends in viral load over time, conduct Confirmation of Virologic Failure Visits when indicated, and consult CMC on management of participants with confirmed virologic failure

31. Scenario

32. MaternalLaboratory Evaluations • Complete blood count (Screening and postpartum Weeks 26 and 50) • CD4+ cell count (Entry and postpartum Weeks 26 and 50) Refer to protocol Appendix II.1 for (general) management guidance

33. MaternalLaboratory Evaluations • ALT, AST, Creatinine, CrCl (Screening; antepartum Weeks 4, 12, 24; Delivery; postpartum Weeks 14, 26, 50; and Post ARV Switch) Grade 1 Grade 2 Grade 3 Grade 4

34. Chemistry Management Guidelines • Refer to protocol Appendix II.3 for asymptomatic ALT and AST elevations • Refer to protocol Appendix II.4 for clinical hepatitis • Refer to protocol Appendix II.5 for increased creatinine and decreased creatinine clearance

35. Recording Test Results on Laboratory eCRFs • All creatinine and CrCl results • All Grade 1 or higher LFT results • All grade 3 or higher hemoglobin, WBC, ANC, and platelet count results • All results that lead to a change of ART regimen • All results that are serious as defined in the DAIDS EAE Manual • All results that are relevant to events that meet criteria for reporting as EAEs *Regardless of whether test was protocol-specified or ordered for clinical purposes

36. Maternal Evaluations

37. Recording onAdverse Event eCRFs • All Grade 3 or higher adverse events • All Grade 2 or higher rashes • All Grade 2 or higher psychiatric events • All suspected or confirmed diagnoses of clinical hepatitis • All adverse events that lead to a change of ART regimen • All SAEs as defined in the DAIDS EAE Manual

38. For both mothers and infants • When available, a diagnosis should be reported as the adverse event term • In addition, signs and symptoms associated with the diagnosis must also be reported if the signs and symptoms meet protocol criteria for adverse event reporting (per protocol Sections 7.2.1 and 7.2.2)

39. Example • Grade 3 malaria • Report diagnosis of malaria • Additionally report fever if grade 3 or higher • Additionally report decreased hemoglobin if grade 3 or higher

40. What are your questions?