Overview of Followup Procedures HOPE Followup Visit Schedule

Overview of Follow-up Procedures

HOPE Follow-up Visit Schedule Screen Enroll M 1 M 2 M 3 M 6 M 9 PUEV Study Exit

Visit Types Monthly Quarterly PUEV Study Exit Interim

Visit Locations Clinic Off-Site

Month 1 & 2 Procedures Administrative: Clinical: ü Review/Update Locator ü Medical/Menstrual ü Schedule Next Visit History ü Reimbursement ü Provide Test Results ü Record/Update AEs Behavioral ü Concomitant Meds* (Counseling): ü Offer/Provide Contraceptives* ü Contraceptive ü Treatment/referrals* ü HIV pre-/post test ü Physical Exam* ü Options Counseling ü Pelvic Exam* (HIV/STI risk reduction and adherence) Study Product/Supplies: Behavioral ü Offer Condoms (Assessments): ü Offer New VR ü Adherence ü Provision of new VR* ü Remove/Collect VR* ü VR instructions* ü Digital Exam* Lab: Urine: ü Pregnancy ü Urine culture* ü GC and CT* Blood: ü HIV-1 Testing ü Plasma Storage ü Syphilis Serology* ü CBC with platelets* ü Serum Chemistries* Pelvic/Other: ü Vaginal Fluid (self) ü Hair ü Used VR* ü Trich or other samples if ind*

Quarterly Procedures Administrative: Clinical: ü Review/Update Locator ü Medical/Menstrual ü Schedule Next Visit History ü Reimbursement ü Provide Test Results ü Record/Update AEs Behavioral ü Concomitant Meds* (Counseling): ü Offer/Provide Contraceptives* ü Contraceptive ü Treatment/referrals* ü HIV pre-/post test ü Physical Exam* ü Options Counseling ü Pelvic Exam* (HIV/STI risk reduction and adherence) Study Product/Supplies: Behavioral ü Offer Condoms (Assessments): ü Offer New VR ü Adherence ü Provision of new VR* ü Behavioral ü Remove/Collect VR* ü Social Harms ü VR instructions* ü ACASI (M 3) ü Digital Exam* Lab: Urine: ü Pregnancy ü Urine culture* ü GC and CT* Blood: ü HIV-1 Testing ü Plasma Storage ü Syphilis Serology* ü CBC with platelets* ü Serum Chemistries* Pelvic/Other: ü Vaginal Fluid (self) ü Hair ü Used VR* ü Trich or other samples if ind*

Differences from ASPIRE? • What do you observe as key differences in follow-up procedures between ASPIRE and HOPE?

Differences from ASPIRE? • More frequent sample collection for adherence measurements (and more sample types!) • Less frequent required physical/pelvic exams • No unique set of procedures for “semi-annual” visits

Visit Checklists

Sequence of Procedures q q Modify to maximize efficiency of clinic flow Very few procedures have required order: § § § q Pelvic Exams Behavioral Assessments before Counseling (but counseling still early on!) Ideally, vaginal fluid swab with ring still in place Ring provision toward end of visit (after clinical/lab assessments and counseling) Recommend pairing Vaginal Ring (VR) removal/insertion Flexibility is encouraged

Clinic Flow q q q Why is efficiency important? What are some strategies that may help improve clinic flow? Regular internal reviews of systems is key - proactive rather than reactive

Study Procedures for Non. Acceptors • With the exception of provision/collection of the study vaginal ring and associated instructions, all study procedures are conducted regardless of whether a participant chooses to accept a ring. – Including collection of blood, swabs, hair

Minimum Procedures for VR dispensation: • AE assessment and reporting (verbal report of symptoms is acceptable; if symptoms indicate that further evaluation is necessary, this must be conducted prior to dispensing study product) • HIV testing and counseling (including RR counseling) and pregnancy testing are required for product dispensation if this has not been done within the past 90 days • Collection of Used Ring (and unused, if applicable), if available • Adherence Counseling/Product Use Instructions, as needed

Making up Missed Procedures • MTN-025 visit windows are contiguous, as such no procedures are required to be “made-up” at subsequent scheduled visits – Effort should be made to make up missed procedures as part of a split visit • Note that in the event of a missed visit, an interim visit may be required to resupply rings (and conduct associated safety assessments and counseling as needed) • If a participant misses her Month 3 visit, ACASI will be considered missed and will not be made up at subsequent quarterly visits

Modified Procedures in the Event of Clinical Hold/Discontinuation • Modified procedures for HIV/pregnancy covered during separate training modules • For all other holds/discontinuations, the only modifications are: – Discontinue ring provision and associated instructions – HIV prevention options counseling will continue and will be tailored to focus on HIV risk reduction plans that do not involve the vaginal ring • Only resume offering study product should the participant be clinically eligible

HIV Prevention Options Counseling During Follow-Up • Provide residual drug feedback, starting at M 3 • Explore how participant is doing with ring use and/or other HIV prevention methods • What went well or did not go well, how the participant is feeling about her HIV prevention approach(es)

HIV Prevention Options Counseling During Follow-Up • Develop HIV risk reduction plan for the coming month(s) – Including her desire to start or continue using the ring as part of her HIV prevention strategy (if relevant), and assessment of confidence in plan • Check-in on attendance to study visits • Provide informational support, as needed

Residual Drug Feedback Counseling Session Residual Drug Data Available Month 3 First Month of Use (i. e. ring collected at Month 1) Month 6 Rings from Months 2 -3 Month 9 Rings from Months 4 -6 Month 12 (PUEV) Rings from Months 6 -9

HIV Prevention Options Counseling Documentation • Chart notes or site-specific worksheet • Document after the session • NOT a summary of procedural steps – focus on capturing participant-specific information • Include enough detail to inform and guide participant’s next session • Mark that counseling was done on visit checklist and whether the participant chooses to use the ring

Month 3 Counseling Considerations • Risk reduction plans should take into account that it may be three months before the participant returns to the clinic for her next visit • Discuss how the participant feels about accepting additional rings at her quarterly visits moving forward

Month 3 Considerations (Cont. ) • Where the participant will store her unused rings and used rings postremoval • Why it is important to change the ring on time each month and how the participant will remember when it is time to change her ring • The importance of not sharings with friends or family members

Month 3 Considerations (Cont. ) • Any questions or concerns the participant has about having extra rings in her possession • Alternatives to accepting additional rings at this visit, as needed (namely, that participants have the option to return to the clinic each month to pick up a new ring if she feels uncomfortable having a supply of two unused rings in her home)

Month 3 Considerations (cont. ) • Provide instructions for tracking order of ring use and information that will be requested about each ring at her next visit – Rate how well she felt she was able to use each ring – Approximately how many days each ring was removed

Month 3 Considerations (cont. ) • Contraceptive method/next dose • What to do in case of suspected pregnancy between visits • What to do in case of suspected HIV exposure between visits

Considerations for Interim Contacts During Quarterly Follow-up Schedule • Consider strategies for supporting participants between quarterly visits with interim contacts such as by phone or through SMS – The goals of these contacts could range from general check -ins, to supporting retention (visit reminders), to supporting ring use or reminders to change rings. – Permission from participant must be provided/documented (e. g. on site locator) • Frequency/content determined by site • Ensure IRB approvals in place, if required

Visits to Pick Up Rings During Quarterly Follow-up Schedule • Visits for the sole purpose of picking up a new ring during a quarterly schedule should be streamlined • The only procedures required are those necessary to collect her used ring and dispense a new ring • Document as an interim visit – What strategies will you use for flagging/fast tracking these visits? – What are your plans for reimbursement of these visits?

PUEV Procedures Administrative: Clinical: ü Review/Update Locator ü Medical/Menstrual ü Schedule Next Visit History ü Reimbursement ü Provide Test Results ü Record/Update AEs Behavioral ü Physical Exam (Counseling): ü Pelvic Exam ü Concomitant Meds* ü Contraceptive ü Offer/Provide ü HIV pre-/post test Contraceptives* ü Options Counseling ü Treatment/referrals* (HIV/STI risk reduction) Behavioral (Assessments): ü Adherence ü Behavioral ü Social Harms ü ACASI (PUEV) Study Product/Supplies: ü Offer Condoms ü Remove/Collect VR* Lab: Urine: ü Pregnancy ü GC and CT ü Urine culture* Blood: ü HIV-1 Testing ü Plasma Storage ü Syphilis Serology ü CBC with platelets ü Serum Chemistries Pelvic/Other: ü Vaginal Fluid (self) ü Hair ü Trich ü Used VR* ü Other samples if ind*

Study Exit Procedures Administrative: Clinical: ü Review/Update Locator ü Medical/Menstrual ü Reimbursement History ü Schedule Next Visit* ü Provide Test Results ü Record/Update AEs Behavioral ü Concomitant Meds* (Counseling): ü Offer/Provide Contraceptives* ü HIV pre-/post test ü Treatment/referrals* ü HIV/STI risk ü Physical Exam* reduction ü Pelvic Exam* ü Contraceptive* Behavioral (Assessments): ü Study Exit Assessment Study Product/Supplies: ü Offer Condoms Lab: Urine: ü Pregnancy ü Urine culture* ü GC and CT* Blood: ü HIV-1 Testing ü Plasma Storage ü Syphilis Serology* ü CBC with platelets* ü Serum Chemistries* Pelvic/Other: ü Vaginal Fluid (self) ü Hair ü Trich or other samples if ind*

Follow-up Pop Quiz Get out your quiz paper!

1. Which of these procedures is required at all scheduled follow-up visits? • Physical Exam • Pelvic Exam • Collection of blood, swabs and hair for adherence measurements • Behavioral Assessments

2. What is the primary difference between monthly and quarterly visit procedures? Monthly Quarterly

3. True or False: With the exception of provision/collection of the study vaginal ring and associated instructions, all study procedures are conducted regardless of whether a participant chooses to accept a ring.

4. Name one consideration for counseling at a participant’s Month 3 visit

5. Which of the following procedures is required prior to providing a ring? A. AE assessment and reporting B. HIV testing and counseling and pregnancy testing if this has not been done within the past 90 days C. Collection of Used Ring (and unused, if applicable), if available D. Adherence Counseling/Product Use Instructions, as needed E. All of the Above

How did you do? ? 1. Required at all visits: Collection of blood, swabs, hair 2. Primary difference between monthly/quarterly: Behavioral assessments done at quarterly visit 3. True: With the exception of provision/collection of the study vaginal ring and associated instructions, all study procedures are conducted regardless of whether a participant chooses to accept a ring. 4. Month 3 Considerations: Varied responses 5. Minimum procedures required to provide a ring: (E) All of the above

Questions?