Planning for HOPE PUEVs and Study Exit Visits

1. Planning for HOPE PUEVs and Study Exit Visits

2. HOPE PUEVs • PUEVs for HOPE participants enrolled on or before 15 Sep 2017 will take place at Month 12 (visit code 8.00) • Participants enrolled between 16 Sep 2017 and 25 May 2018 will have abbreviated follow-up schedules ending with a PUEV visit around Sep/Oct 2018

3. PUEV Procedures • PUEVs include most follow-up visit procedures, with the following modifications: • HIV prevention options counseling will be modified to focus on risk reduction plans without the dapivirine ring • Use “End Visit, Month 12” Options Flipchart • Review Options Manual pg. 34-41, recommend mocks • No vaginal rings are offered • For participants who ever accepted a ring: Complete vaginal ring request slip for “Product Use Period Completed” and send to pharmacy. • Do NOT complete Product Hold/Discontinuation CRF

4. PUEV Procedures (Cont) • PUEVs include most follow-up visit procedures, with the following modifications: • Conduct a physical and pelvic exam • Complete testing for GC/CT, Syphilis, and Trichomonas • Collect blood for serum chemistries/CBC • Complete BA (note additional questions), Vaginal Practices, and Social Influences CRFs • Administer PUEV/Discontinuers ACASI

5. Study Product Considerations • It is expected that participants will return their VRs during the PUEV visit (used and unused). • All VRs remaining in the participant’s possession should be returned by the SEV (at the latest). • If the participant does not bring her remaining VRs (used or unused) to the SEV, study staff must arrange to retrieve the VR within 5 business days • If the study product(s) are not retrieved within that timeframe, the MTN-025 PSRT must be informed.

6. Seroconversion at PUEV • If a participant has a positive rapid HIV test at PUEV: • If a final HIV positive status is confirmed at PUEV (based on Geenius completed on that day) then scheduling the SEV is not necessary.  • If the participant is confirmed HIV negative, or if her status is not resolved as of the time of PUEV, then then scheduling of the SEV should proceed.  • HIV testing may be omitted from the Study Exit Visit if the participant completed algorithm testing and was determined to be HIV-infected prior to the visit.

7. CRF Completion for PUEV • Required Visit 8 - PUEV CRFs • Date of Visit • Follow-up Visit Summary • Behavior Assessment (+Y/N prompt) • Vaginal Practices (+Y/N prompt) • Social Influences Assessment (+Y/N prompt) • Ring Adherence (+Y/N prompt) • ACASI Tracking (+Y/N prompt) • HIV Test Results • Pregnancy Test Results • Specimen Storage • Concomitant Medications Log Y/N • Pelvic Exam (+ Pelvic Exam Diagrams non-Rave form) • Ring Collection and Insertion • Additional Study Procedures Y/N • Physical Exam • Vital Signs • Adverse Experience Y/N • Laboratory Results • STI Test Results

8. CRF Completion for V8 - PUEV • On the Follow-up Visit Summary CRF, select “PUEV” as the response for “Is this visit a PUEV, scheduled Study Exit Visit, or an early Termination?” item: • Behavior Assessment, Vaginal Practices, & Social Influences Assessment CRFs available in local language • Complete the PUEV/Discontinuers ACASI assessment if not previously completed and document on the ACASI Tracking CRF

9. Study Exit Visits (SEVs) • SEVs will occur approximately 4 weeks after the PUEV (**Use SEV calculator**) • Exception: no SEVs for Seroconverters (seroconverters will be terminated at PUEV) • Minimum of 2 weeks between a participant’s PUEV and SEV. • If a participant misses her scheduled Study Exit Visit, efforts to complete this visit should continue until the end of the study, after which no further study visits will occur.

10. SEV Visit Calculator

11. SEV Procedures • SEVs include most follow-up visit procedures, with the following modifications: • No HIV prevention options counseling is completed, however, participants still receive HIV risk reduction counseling per site SOPs • No vaginal rings are routinely offered or collected • Study Exit Assessment (behavioral CRF) is completed • Contraceptive counseling only occurs if indicated (note this is recommended per standard of care) • Next visit scheduling only occurs if indicated

12. Seroconversion at SEV • If the participant has positive rapid(s) at her Study Exit visit, complete algorithm testing and additional required sample collection. • If the confirmatory test is positive, refer the participant for treatment and complete termination visit procedures on that same day. • If the confirmatory test is negative or indeterminate, query the LC as required by protocol and notify the management team for guidance. Do not complete termination visit procedures until her HIV status is finalized. • This participant is still eligible for MTN-015 after exit from ASPIRE since she seroconverted during participation in the parent protocol. Approach for enrollment once algorithm confirms HIV infection per protocol; recommend as soon as possible to avoid loss to follow-up.

13. Termination Procedures • The following procedures are unique to the Termination Visit (PUEV for seroconverters, SEV for all other participants): • Completion of the Termination Form • Review all AEs that meet the protocol safety endpoint definitions (related G2, all G3/G4 AEs, and all SAEs) to confirm relationship status, AE grade, and outcome are accurately documented in the participant record. • Complete documentation of how best to contact for study results, as well as permission to contact for future research, in particular 032/AHA • Template study exit worksheet and permission to contact logs available on MTN website • Follow up referrals for ongoing care post-study should be provided as needed

14. CRF Completion for V9 - SEV • Date of Visit • Follow-up Visit Summary • Study Exit Assessment (+Y/N prompt) • HIV Test Results • Pregnancy Test Result • Specimen Storage • Concomitant Medications Log Y/N • Adverse Experience Y/N • Additional Study Procedures Y/N • Termination

15. CRF Completion for V9 - SEV • Things to consider: • On the Follow-up Visit Summary CRF, select “scheduled Study Exit Visit” as the response for “Is this visit a PUEV, scheduled Study Exit Visit, or an early Termination?” item: • Study Exit Assessment CRF available in local language

16. CRF Completion at Study Termination • Things to consider: • Review all AE and Concomitant Medications Log CRFs to ensure each is closed or marked as “continuing at end of study participation” or “continuing at end of study”, respectively. • Review each completed Social Impact log CRF to ensure that a resolution date is provided or that ‘unresolved at end of study’ is selected for the item “Record current status”.

17. CRF Completion at Study Termination • Things to consider: • Complete “Was the participant instructed to resume study product use” for any open Clinical Product Holds • Ensure that for every vaginal ring dispensed per the Pharmacy Ring Dispensation, there is an associated log line and ‘stored/not stored’ status for that ring.

18. CRF Completion at Study Termination • Things to consider: • Double check all forms (with exception of Additional Study Procedures Y/N) are completed within participant’s casebook, including Y/N admin forms • Pregnancy Outcomes for all pregnancies ongoing at Termination must be obtained and recorded on the Pregnancy Outcome CRF • No date within the RAVE database should be after the participant’s termination date specified on the Termination CRF.

19. Considerations for Pregnant Participants • Participants who are pregnant at the SEV will continue to be followed until the pregnancy outcome is ascertained (or, in consultation with the PSRT, it is determined that the pregnancy outcome cannot be ascertained) • Offer enrollment or continue follow-up for MTN-016, as appropriate

20. AEs Requiring Follow-up • A subset of AEs must be followed after a participant's termination • Ongoing SAE/EAEs at termination • AEs that are found to have increased in severity at termination • For AEs that are continuing at the termination visit but do not meet the criteria above, it is left to the discretion of the IoR/designee as to whether the AE needs to be followed. The PSRT can be consulted as needed.

21. Frequency of Follow-up on AEs • IoR/designee must establish a clinically appropriate follow-up plan for AEs requiring follow-up • At a minimum, re-assess 30 days after SEV • Additional evaluations also may take place at the discretion of the IoR/designee • Continue to reassess at least once per month while the study is ongoing until resolution or stabilization • If the AE has not resolved by study end (i.e., once all participants are exited), these AEs should be re-assessed at least once more within 30-60 days after the study end date

22. Participant Contacts after Termination • After the Termination visit, a ‘final contact’ may be needed for some participants to ensure test results are provided and/or AEs are followed up as needed. • NO CRFs are completed for these final contacts, but these contacts should be documented in the chart notes.

23. Preparing for PUEV/SEVs • Start to educate and prepare participants starting at their Month 9 visits (or between Month 9 and PUEV) • Familiarize yourself with PUEV/SEV CRFs in Medidata MTN-025 TRAIN database • Reviewing current PUEV/Termination visit checklist to ensure up to date

24. Thank you!