HOPE Study Screening & Enrollment Procedures

1. Overview of Screening Visit Procedures, PTID Assignment, Screening & Enrolment Logs, and Screen Failures

2. To keep in mind during screening & enrollment What do we want to learn from HOPE? • When offered the ring as a CHOICE, will women use it with high adherence and safety, and achieve HIV protection? • How acceptable and feasible is the delivery of the microbicide vaginal ring?

3. Components of Screening Visit Slide 1 • Questionnaires: • Demographics • Screening Behavioral Eligibility Administrative: • Screening IC • Assign PTID • Assess eligibility • Locator • Schedule Next Visit* • Reimbursement Behavioral: • HIV pre- & post-test • HIV/STI risk reduction (offer condoms) • Contraceptive counseling

4. Components of Screening Visit Slide 2 Clinical: • Medical/Menstrual Hx • Concomitant Meds • Contraceptive provision* • Physical Exam • Pelvic Exam • Treatment or referral* Laboratory: Urine: • Pregnancy • GC/CT • Urine culture*† Pelvic: • Trichomonas • Pap Smear* Laboratory: Blood: • HIV Serology • CBC with platelets • Serum Chemistries • Syphilis Serology

5. Screening Window Enrollment Screening 56 Days If needed, screening visit procedures can be completed over multiple visits. There is no limit to screening attempts

6. Screening Visit Checklist

7. Screening Informed Consent

8. MTN-025/HOPE Inclusion Criteria • Previously enrolled in MTN-020 (ASPIRE) • Able and willing to provide written informed consent • Able and willing to provide adequate locator information • HIV-uninfected • Using an effective method of contraception at Enrollment, and intending to use an effective method for the duration of study participation. Effective methods include hormonal methods (except contraceptive ring); intrauterine contraceptive device (IUCD); and sterilization (of participant, as defined in site SOPs) • Agrees not to participate in other research studies involving drugs, medical devices, vaginal products, or vaccines for the duration of study participation

9. MTN-025/HOPE Exclusion Criteria • Study product use permanently discontinued in response to an AE or safety related concern while taking part in the MTN-020 (ASPIRE) trial • Per participant report at Screening: • Plans to relocate away from the study site during study participation • Plans to travel away from the study site for more than three consecutive months during study participation • Per participant report at Enrollment, currently taking Post-Exposure Prophylaxis (PEP) PEP use at Screening is not exclusionary. Participants may be enrolled after the PEP regimen is complete and a negative HIV test is documented within 56 days of providing informed consent for Screening. • With the exception of MTN-020 (ASPIRE), participation in any other research study involving drugs, medical devices, vaginal products, or vaccines, within 60 days of enrollment Participation in the ‘Decliner Population’ does not preclude MTN-025 full study participation in the future.

10. MTN-025/HOPE Exclusion Criteria • Is pregnant at Screening/Enrollment or planning to become pregnant in the participant’s anticipated study participation period • Is currently breastfeeding • Diagnosed with urinary tract infection (UTI), pelvic inflammatory disease (PID), STI or reproductive tract infection (RTI) requiring treatment per WHO guidelines Note: Otherwise eligible participants may be enrolled after completing treatment if all symptoms have resolved. • Clinically apparent Grade 3 pelvic exam finding

11. MTN-025/HOPE Exclusion Criteria • Has any of the following laboratory abnormalities at Screening Visit: • Aspartate aminotransferase (AST) or alanine transaminase (ALT) > Grade 3 • Creatinine > Grade 3 • Hemoglobin > Grade 3 • Platelet count > Grade 3 • Pap result ≥ Grade 3 • Has any significant medical condition or other condition that, in the opinion of the IoR/designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives

13. Questions on Screening procedures?

14. PTID Name Linkage Log

15. Enrollment Screening Screen Fail

16. Documentation for Screen Failures • Screening IC forms (IC/coversheet). • Document reasons for ineligibility and date of determination as per the Eligibility Checklist • ECI-1 and pre-screening CRF only – complete and enter into Medidata • Document necessary referrals in ppt’s file; document that clinically significant abnormalities were communicated to ppt (Ex. Grade 3 lab value) • Make sure all screening documentation is complete up until the time that ineligibility was determined, including screening visit Checklist • File or enter data for all documents per MTN Data Management SOP

17. Screening Pop Quiz Get out your quiz paper!

18. Screening Pop Quiz • If a participant screens out of HOPE, can she participate in the HOPE decliner group?

19. Screening Pop Quiz • How many screening attempts can be made for each participant?

20. Screening Pop Quiz • Name one difference between the eligibility criteria for HOPE and ASPIRE.

21. Screening Pop Quiz • Where does the pre-screening ID come from?

22. Screening Pop Quiz • How many days long is the screening window?

23. Screening Pop Quiz How did you do? • NO - Only participants who actively decline study participation (i.e., express disinterest in enrollment) should be considered for decliner group enrollment. • Trick question! No limit. • Variable • Medidata! • 56 days long

24. Screening Visit References • Eligibility criteria protocol Sections 5.2/ 5.3 • Screening procedures protocol Section 7.2; SSP Section 4 • Visit Checklist Templates MTN Website

25. ANY further questions?