Overview of Screening Visit Procedures, Eligibility Criteria, and Visit Flow

1. Overview of Screening Visit Procedures, Eligibility Criteria, and Visit Flow

2. Screening Visit Procedures • What are 2 the primary goals of the screening visit procedures? • Evaluate Eligibility • Establish Baseline

3. Eligibility Criteria - Rationale Rationale is to select participants who are • Healthy but at risk for HIV infection • Likely to be retained • Likely to be adherent to product use plan • At low risk for safety issues potentially associated with product use

4. Inclusion Criteria Protocol Page 23 • Age 18-45 • Able/willing to provide IC   • Adequate locator info • HIV-uninfected   • Sexually Active • Effective contraception use/intention • Agrees not to participate in other research studies

5. Exclusion Criteria IVDU in past 12 months Gynecologic or genital procedure or pregnancy outcome w/in 90 days Participation other research study w/in 60 days Participation in VOICE/other PrEP studies w/in 12 months AST, ALT, or platelet count Grade 1 or higher Creatinine, hemoglobin, or pap result Grade 2 or higher IoR Discretion • Pregnancy intention or currently pregnant • Currently breastfeeding • Plans to relocate • Travel away for >8 weeks • Ongoing/untreated UTI • STI/RTI requiring treatment • ≥Grade 2 Pelvic Finding • Known adverse reaction to study product or latex • Chronic vaginal candidiasis • Uncontrolled chronic condition • PEP in past 6 months

6. Exclusion Criteria Timeframes Screening Visit Timeline Non-therapeutic IV drug use > 4 episodes vag candidiasis -No Vaginal Intercourse 12 mos 6 months 90 days 60 days Screening Enrollment 28 days Ppt in VOICE or other PrEP studies -Ppt in Research involving meds/devices -Gyne/Genital Procedure -PregOutcome PEP Enrollment Visit Timeline

7. Page 3 Components of Screening Visit • Administrative: • Screening IC • Assign PTID • Assess eligibility • Locator • Schedule Next Visit* • Reimbursement Clinical: • Medical/Menstrual Hx • Concomitant Meds • Contraceptive provision*† • Physical Exam • Pelvic Exam • Treatment or referral* Laboratory: • Urine: • Pregnancy • GC/CT • Urine culture*† • Pelvic: • Trichomonas • Herpes Lesion*† • Wet mount for candidiasis or BV*† • Pap Smear* • Vaginal pH • Gram stain • Endocervical swab • Behavioral: • HIV pre-/ post-test • HIV/STI risk reduction (offer condoms) • Contraceptive Laboratory: Blood: • HIV Serology • CBC with platelets • Serum Chemistries • Syphilis Serology • Questionnaires: • Demographics • Screening Behavioral Eligibility LoA#1

8. Screening Window Enrollment Screening 28 Days If needed, screening visit procedures can be completed over multiple visits. One rescreen is allowed

9. Page 39 Screening Visit Checklist

10. ASPIRE Informed Consents Screening Enrollment • Off-Site Specimen Storage • IDIs/FGDs • LoA#2 • Subset • Spilhaus • Can defer to M1 • Long Term Optional

11. Page 23 Screening Informed Consent

12. Page 27 Informed Consent Tools • Fact Sheets (5 total) • IC Booklet • IC Tabletop Flip Chart • Ring Use Instructions/Important Information sheet • Pelvic model & sample ring

13. Questions on Screening procedures?

14. Screening VisitCASE REPORT FORMS

15. Approach to ASPIRE CRF Training • Focus on purpose/reason for each CRF • Will try to address questions we received during the external review of the CRFs • Will not go item by item, but will practice form completion using scenarios • Will not review form instructions, but will refer to these as needed • CRFs can be found in your binder – Screening tab • Questions from all encouraged - Let’s get started!

16. Page 49 Demographics (DEM-1) • Not interviewer-administered/translated • Collects required ppt descriptors (age, ethnicity) and descriptors requested for publications/reports • For drinks/week and cigarettes/day items, use estimates and rounding as needed – does not have to be exact • Cell phone & ‘income on her own’ questions used to describe participant SES • Question on travel time to the clinic used to assess ppt burden and may relate to retention • Items reflect participant information at the time of her SV only – not updated later unless correction is needed

17. Page 51 Screening Behavioral Eligibility CRF • Ensures ppt behavioral eligibility items are asked and documented in the same way across sites and ppts • Interviewer-administered; in local language(s) • Practice before administering for 1st time • Read items aloud as they appear • provide clarification as needed • Complete all form items even if ppt provides response that indicates she is not eligible • Note item 17 includes IPM 027 participation • Will be clarified in a Data Communique • Review closely once completed to ensure all items are completed as needed • Reference form when completing matching items on Eligibility Checklist

18. Page 55 Screening Menstrual History (SMH-1) • Created to help sites document items relevant to a ppt’s baseline menstrual history and bleeding pattern • Is DataFax – data will go into the study database • Items 3-7: complete based on the ppt’s usual menstrual periods as experienced prior to the SV • if ppt is amenorrheic (consistently or partially), complete items based on the how the ppt describes her most recently-experience menstrual periods and provide additional details as needed in item 8. • If the participant reports more than 99 days between her usual menses, record “99” for item 3 (maximum boxes) and provide more details in item 8

19. Page 55 SMH-1 continued… • Item 6 (last menses day) – mark “ongoing” if on menses at SV; do not need to update at EV • Item 8 • Describe as best as possible participant’s baseline bleeding pattern and associated symptoms • Update as needed at EV if bleeding pattern or symptoms changes (Ex. due to new HC method) • Per note at bottom, update PRE CRF as needed with baseline irregular bleeding/menstrual symptoms

20. Page 57 Screening Visit Physical Exam (SPX-1) • DataFax form • All items require a response – all systems listed in ‘Findings’ portion of the form required to be evaluated • Use Notes line to describe abnormal findings • Option to use notes line to describe normal findings as well (ex. normally healed scar) • Make sure Staff Initials/Date are in order if one person does vitals and a separate person does the exam assessments (use brackets as needed) • Record medically-relevant findings onto PRE CRF (per previous presentation)

21. Page 59 Pelvic Exam Diagram (non-DataFax) • Used as the source document for all normal and abnormal pelvic exam findings • When completing, keep in mind that someone else may look at this form prior to the participant’s next pelvic exam. Be descriptive! • Record all abnormal findings on the Screening Pelvic Exam CRF (diagrams form is source)

22. Page 61 Screening Pelvic Exam (SPE-1) • Completed at SV to all abnormal pelvic exam findings observed • Columns arranged by location with a general ‘other’ column • Lists abnormalities using terms in FGGT and CONRAD manual • Record abnormal findings on PRE CRF per note below items 1b, including location • If a 2nd (repeat) screening pelvic exam performed, complete new SPE-1 and PE Diagrams; fax repeat SPE-1 only once enrolled

23. Page 63 Pre-existing Conditions Log (PRE) • Used to document in one place each participant’s baseline medical/menstrual history • Will include ppt-reported conditions as well as abnormalities captured on: • Pelvic Exam Diagrams, Screening Pelvic Exam CRFs • Screening and Enrollment Physical Exam CRFs • Grade 1 and higher laboratory results on Screening Lab Results CRF • Newly-diagnosed (at SV) STIs per Screening STI Test Results CRF

24. Pre-existing Conditions CRF – con’t • Page number – start with 01, go up as needed • Condition • Follow guidelines for AE text except do record past surgeries as needed • Be as descriptive as possible • Onset Date (Month and Year) • If uncertain, use best estimate; year required • Comments • Add info on frequency and duration of chronic condition outbreaks; other relevant info for the “snapshot”

25. Pre-existing Conditions CRF – con’t • Ongoing at Enrollment? • Leave blank at SV if ongoing; complete at EV • Chronic/recurrent diagnoses are ongoing • Severity Grade • Assess per Tox Table and FGGT • Mark “not gradable” if condition is below Grade 1 or resolved at time of report (ex. C-section entry) • At Enrollment Visit: • If condition has resolved, do not update severity grade • If severity grade has or on or prior to EV, update as needed • Review all PRE CRF pages at SV and EV to ensure a complete medical history (including current conditions) is created • Info may be needed for Clinical Queries or auditors months or years after originally-recorded

26. Pre-existing Conditions CRF – con’t • Entries can be added and modified post-enrollment • Ppt may have forgotten to report a symptom • Perhaps something that was thought to be not relevant is later considered relevant; if so, add to PRE • May need to collapse signs/symptoms into a diagnosis • Write a chart note to explain why an entry is being added/modified during follow-up • Document meds taken for PRE on Concomitant Medications Log CRF

27. Page 65 Concomitant Medications Log (CM-1) • Completed starting at the SV; updated as needed at EV and during follow-up • Record trade name whenever possible; if not, use generic name • For injectable contraceptives, record separate entry for each injection • For OCPs, record one entry for each pill pack • For all other injectable treatments, document single entry for tx. • If exact dose/units not known, put best description possible • “Taken for AE” item will always be ‘no’ for entries at SV • For each contraceptive entry, record a response for “If contraceptive, was it dispensed at research center?” • Update PRE CRF if CM completion reveals conditions not already reported or observed

28. Page 67 Screening Specimen Storage (SSS-1) • Documents collection of the 2 SV stored specimens • Vaginal Smear for gram stain • Endocervical swab • Blood visible on swab?: used to inform swab analyses done at Network Lab • Mark specimens as “stored” if collected and sent for storage; update if you find out later that specimens were not stored • Also collects results of syphilis testing • Complete only 1 CRF for each participant per screening attempt • Will not collect specimens for storage or complete form if a repeat 2nd pelvic exam is done

29. Page 69 Screening Visit LDMS Tracking Sheet Optional Note Visit Code of SV is pre-printed = 97.0

30. Page 71 Screening Laboratory Results (SLR-1) • Complete CRF as SV results become available • If severity grade box present, assess for severity grade per Tox Table • If below grade 1, leave box blank • If Grade 1 or higher, add to Pre-existing Conditions form • Notes on eligibility are present when applicable • If some or all tests are repeated prior to randomization: • Complete a new SLR • Only fax 2nd SLR CRF completed, once ppt enrolls OR • Use Alternate Collection Date if not all results on CRF repeated

31. Page 71 Screening Laboratory Results (SLR-1) Using alternate collection date to update partial lab results

32. Page ?? Screening STI Test Results (SST-1) • Captures results of Trich, GC, CT tests done at SVA • Will also capture wet mount results, if done • If any STIs diagnosed, record on PRE CRF • Will allow us to report on how many ppts had STIs prior to enrollment • Vaginal fluid pH assessed only if clinically indicated

33. Page 73 Eligibility Criteria (ECI-1) • Allows SCHARP to report on # ppts screened, # enrolled, # screen fails and reasons for screen fails • Item 3: • “participant did not complete all screening procedures” – ppt was eligible but did not complete all screening procedures (including EV) • “Eligible but declined enrollment” – participant was eligible but she chose not to enroll • “Not eligible” –ppt completed procedures as planned but does not meet all eligibility criteria • Item 4: Mark all reasons that apply • 4g: Mark if ppt participant in VOICE or other HIV prevention trial using antiretroviral medication in the past 12 months • Included in the SV form packet; complete only if screen fail • Move to EV packet and complete then if EV scheduled

34. Screening Visit QA/QC • Before ppt leaves: • Review visit checklist for completeness • Review Screening Behavioral Eligibility Criteria form for completeness • Make sure lab requisition docs/LDMS Sheet and lab specimens are in order • Review pelvic exam/physical exam forms and make sure all needed items are on PRE • Make sure you have a way to be alerted once local lab results come back (or don’t come back) • Complete SLR, SST, PRE as needed, Eligibility Checklist as needed • Do not fax any forms until ppt enrolls; fax ECI if ppt will not proceed to EV • Make sure systems are in place for EV, including scheduling, ppt files, Pharmacy is aware of potential EV, etc.

35. DataFax Overview Video – Atlas

36. Additional Tools

37. Page 75 Eligibility Checklist

38. Page 81 PTID Name Linkage Log

39. Page 83 Screening Enrollment Screening Screen Fail

40. Documentation for Screen Failures • Save IC forms (IC/coversheet). • Document reasons for ineligibility and date of determination as per the Eligibility Checklist • ECI-1 CRF – complete and fax to SCHARP (do not fax any other CRFs for the ppt). • Document necessary referrals in ppt’s file; document that clinically significant abnormalities were communicated to ppt (Ex. Grade 3 lab value) • Make sure all SD is complete up until the time that ineligibility was determined, including SV Checklist • File all documents per MTN Data Management SOP

41. Page 85 Last Day to Enroll Calculator

42. Additional Tools • Participant Tracking Database • Coenrollment database/system

43. Activity

44. Screening Visit Activity • Pair up with the person sitting next to you • Everyone will receive a screening packet of CRFs/source documents. This participant has completed her screening visit, and all labs are currently pending. • Complete the screening visit column on the Eligibility Checklist in your training binders to evaluate/document her eligibility thus far.

45. Screening Visit References • Eligibility criteria protocol Sections 5.2/ 5.3 • Screening procedures protocol Section 7.2 • Accrual SSP Sections 4.2.1 – 4.3.4 • Visit Checklist Templates SSP Section 7