Welcome to the webinar 1 The session will begin shortly. While you

Welcome to the webinar 1 The session will begin shortly. While you wait, follow these steps to set up your zoom and locate the interactive tools we will use today 1. Please mute your line 2. We encourage turning your video on, if possible 4. At the top of your screen, go to ‘view options’ to open the annotate toolbar. Note the ‘text’, ‘draw’ and ‘stamp’ tools 3. Open the chat panel – say “hi” and type your name and site 5. The ‘reactions’ feature can be used to raise hand or provide other feedback

Let’s Practice 2 Test the annotation tools. Put a ‘check’ stamp of the country you are living in: Use the reactions to give a ‘thumbs up’ when you are ready to begin!

3 Reminder: Document this training. Study IoRs are responsible for ensuring that study staff members are adequately trained to serve their designated site- and study-specific functions. Per the DAIDS Site Clinical Operations and Research Essentials (SCORE) Manual, all sites must establish and follow a standard operation procedure (SOP) for personnel training and certification documentation. Each IoR (or designee) is responsible for documentation of each study staff member completing study-specific training modules and webinars corresponding to their designated role. This documentation must be on file at the site and available for inspection/monitoring at any time, and per this SOP.

4 Sample Training Documentation Template available on DAIDS website: Division of AIDS (DAIDS) Site Clinical Operations and Research Essentials (SCORE) Manual NIH: National Inst itute of Allergy and Infectious Disease s

5 Agenda: General Protocol v3.0, Session 1 Duration 10 min Topic Welcome, Zoom Training Orientation, Review of Agenda 15 min Study Overview 15 min 15 min 25 min 10 min Eligibility Criteria Informed Consent SOE (Part 1): Screening and Enrollment Q&A Presenter(s) Emily Brown, FHI 360 Lynda Stranix-Chibanda and Ben Chi, IMPAACT 2009 Protocol Chairs Ashley Mayo, FHI 360 Ashley Mayo, FHI 360 Emily Brown, FHI 360 All

IMPAACT 2009 Pharmacokinetics, Feasibility, Acceptability, and Safety of Oral Pre-Exposure Prophylaxis for Primary HIV Prevention during Pregnancy and Postpartum in Adolescents and Young Women and their Infants. Protocol Version 3.0 with CM #1 Lynda Stranix-Chibanda and Ben Chi, IMPAACT 2009 Protocol Chairs 23 August 2021

7 Background and Rationale https://aidsinfo.unaids.org/ Incident HIV during pregnancy and while breastfeeding contributes a significant proportion towards new paediatric HIV infections globally. Primary prevention during this time was named a priority by WHO and UNAIDS.

8 Background and Rationale Oral PrEP with TDF-FTC has been shown to be effective for HIV prevention in numerous settings, however, this is highly dependent on adherence PrEP is being provided in pregnancy in many areas, now, albeit with low uptake A deeper understanding is still needed about what support young women need for daily oral PrEP to be feasible and acceptable during pregnancy and while breastfeeding Further to this, additional safety data is required

9 Background and Rationale Even though new PrEP modalities are being studied, understanding adherence support needs and acceptability will remain important to give all women a choice of HIV prevention products.

10 IMPAACT 2009 PK Results Study Population: 40 women enrolled from March-May 2019. 3348 of 3360 ( 99%) total doses were directly observed. All participants met criteria for inclusion in the analysis. Characteristic median (IQR) Pregnant (N 20) Postpartum (N 20) Age (yrs) 20 (19.5, 22.5) 20 (19, 22) Gestational Age (wks) 18 (15, 20) NA Weight (kg) 59 (56, 65) 55 (51, 62) Postpartum (wks) NA 7 (7, 9)

IMPAACT 2009: Observed results Dashed line USA median (1540); grey shading 95% CI for loess 11 Confidential Draft

12 IMPAACT 2009: Modeled results Dashed line USA median (1540); grey shading 95% CI for loess Confidential Draft

13 IMPAACT 2009 PK Results TFV-DP concentrations in DBS were approximately one-third lower in pregnancy compared to post-partum These results are critical to understanding adherence to PrEP in pregnant and postpartum women, one of the primary objectives for the PrEP comparison component The PK component results will directly inform the drug level feedback provided as part of targeted integrated Next Step Counseling (t-iNSC) Additional information in Protocol Section 1.3.3.1

14 Drug Level Feedback Zones

15 PrEP Comparison Component: Study Design Design: Parallel observational cohort study Women will be enrolled prior to 32 weeks’ gestation. They will choose to enter one of two cohorts: Cohort 1: those who agree to initiate PrEP. Cohort 2: those who decline to initiate PrEP.

16 Study Design All women will receive: Standard of care HIV prevention services Study-specific behavioral risk reduction intervention Antenatal, delivery, and early infant care via mHealth messaging service

17 Study Interventions Intervention: Both Cohorts: Behavioral HIV risk reduction package, including cohortappropriate SMS messages throughout follow-up. Cohort 1 only: Daily oral PrEP (200mg FTC/ 300mg TDF) throughout follow-up. Enhanced adherence support, including SMS messaging and feedback of drug levels with tailored counseling.

18 Study Purpose and Population Purpose: To determine among HIV uninfected young women and their infants, the feasibility, acceptability, and safety of oral pre- exposure prophylaxis (PrEP) during pregnancy and postpartum. Population: Pregnant HIV-uninfected women, 16-24 years of age, with a confirmed singleton pregnancy of 32 weeks’ gestation or less, and their infants.

19 Sample Size and Study Duration Sample Size: Approximately 350 women to achieve at least 300 evaluable (200 in Cohort 1 and 100 in Cohort 2) and their infants. Study Duration: Approximately 24 months total. Women will be accrued over a 12-month period and followed through 26 weeks postpartum. Length of follow-up will vary based on gestational age at enrollment, expected to last until infant is 6 months old.

20 PrEP Comparison Component: Primary Objectives To characterize PrEP adherence among HIV-uninfected young women during pregnancy and for twenty-six weeks postpartum, when provided with enhanced adherence support through mobile technology and counseling based on observed drug levels. To assess the safety of FTC/TDF for PrEP during pregnancy and postpartum by comparing pregnancy outcomes and maternal and infant safety outcomes between cohorts.

21 PrEP Comparison Component: Other Other Objectives To identify individual, social, and structural barriers and facilitators to PrEP uptake during pregnancy, and to adherence during pregnancy and postpartum. To compare reported sexual risk behaviors and incidence of sexually transmitted infections, including HIV infection, among women who initiate PrEP during pregnancy versus women who decline PrEP.

22 PrEP Comparison Component: Other Objectives (Cont.) To compare antiretroviral drug resistance among women and infants who acquire HIV with and without exposure to FTC/TDF for PrEP, including whether resistance was transmitted or acquired at time of transmission. To compare bone density in women who initiated PrEP during pregnancy and women who decline PrEP.

23 PrEP Comparison Component: Exploratory Objective To describe the composition of and changes in the maternal vaginal and gut microbiome and infant gut microbiome according to PrEP exposure.

24 Study Sites Uganda (Kampala) Baylor-Uganda CRS 31798 MU-JHU Care Limited CRS 5126 Malawi (Blantyre) Blantyre CRS 30301 Zimbabwe Seke North CRS 30306 Harare Family Care CRS 31890 St. Mary’s CRS 30303 South Africa (Johannesburg) Wits RHI Shandukani Research Centre CRS 8051

25 Pop Quiz #1 Women who join IMPAACT 2009 are randomized at entry to initiate daily oral PrEP in pregnancy (immediate) or at 12 weeks postpartum (delayed). - True - False

26 Questions? Please raise your hand or type your questions into the chat box.

IMPAACT 2009 PrEP Comparison Component: Eligibility Criteria Protocol Version 3.0 with CM#1 Ashley Mayo, FHI 360 23 August 2021

28 Protocol References 4.2.1 4.1.2 Inclusion Criteria: Cohorts 1 and 2 Exclusion Criteria 4.2.3 Step 2 Inclusion Criteria: Cohort 2 only 4.3 Infant Enrollment

29 Pop Quiz #2 Which of the following is a key difference in the PrEP comparison component population eligibility criteria compared to the PK component? a) The gestational age range is broader b) Participants need regular access to a cell phone c) PrEP component participants can decline PrEP d) Participants are in follow-up for longer e) PrEP component participants must be literate f) All of the above

30 PrEP Component Population: Key Differences Gestational Age 32 weeks Participants followed through 26 weeks postpartum Protocol ref: 4.2.1.2 Regular access to cell phone: Cohort 1: send/receive SMS Cohort 2: receive SMS Protocol ref: 4.2.1.9 Cohort 1: willingness to take PrEP Cohort 2: unwillingness to take PrEP Protocol ref: 4.2.1.11 Protocol ref: 4.2.1.10 Participant must be literate Protocol ref: 4.2.1.13

31 At Screening, Gestational Age 32 weeks* Defined as 224 days or less after the date of conception Ultrasound scans are required to confirm singleton pregnancy, and to confirm/ determine gestational age If adequate sonographic results are not available from medical records at screening, schedule an ultrasound so that results are available prior to enrollment. *NOTE per protocol 6.2.1.1: For eligible women, enrollment must occur in time for study drug initiation prior to 32 completed weeks of gestation.

32 Requirements for Fetal Ultrasound Minimum requirements for ultrasound result reports: Date of scan Number of fetuses Biometry measures: If 14 weeks gestation: Crown-rump length If 14 weeks gestation: Femur length, abdominal circumference, and either or both head circumference and biparietal diameter Calculated gestational age on the date of the scan or estimated date of delivery

33 Re-dating gestational age based on U/S If the estimated gestational age by the participant’s LMP differs from the ultrasound estimate by more than these accepted variations, the ultrasound estimate of gestational age should be used instead of the participant's LMP estimate. American College of Obstetricians and Gynecologists (ACOG): https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/05/methods-for-estimating-the-due-date

At your site, what questions will you ask to determine whether a potential participant Is willing or unwilling to initiate PrEP through 26 weeks postpartum? Has access to cell phone that can receive (cohort 2) or send/receive (cohort 1) SMS? Intends to stay within the study site’s catchment area for at least 26 weeks postpartum? Is literate? 34

35 Age and Informed Consent At study entry, age 16-24 years Confirmed by site SOPs Willing and able to consent for self/baby (or for minors, parental/guardian consent for mom/baby with assent) Protocol ref: 4.2.2.1 Determined by site SOPs and consistent with site IRB/EC policies See also DAIDS SCORE manual for age/identity verification requirements

36 Laboratory Eligibility HIV Negative at Entry Within 14 days prior to entry, negative by HIV RNA test At study entry, HIV rapid test negative and absence of symptoms of acute HIV infection (i.e. acute viral illness) Protocol ref: 4.1.1.5 & 4.1.1.6 At Screening, has following labs: Negative Hepatitis B surface antigen test Grade 1 or normal ( 2.5 x ULN) ALT Grade 1 or normal ( 9.5g/dL) HB Grade 1 or normal ( 800cells/mm3) ANC Normal ( 90mL/min) for estimated creatinine clearance (CrCl; CockcroftGault formula) Negative or trace proteinuria ( Grade 1). Normal dipstick urine for glucose ( Grade 1) Protocol ref: 4.1.1.7, 4.1.1.8, 4.1.1.9, & 4.1.1.10 Weight: At study entry, mother weighs 35 kg Protocol ref: 4.1.1.11

37 Pop Quiz #3 Exclusion criteria for the PrEP component are the same as for the PK component? a. True b. False

TRUE: Exclusion Criteria for the PrEP component are the same as the PK component 38

39 PrEP Component Exclusion Criteria 4.1.2.1 Current significant uncontrolled active or chronic disease 4.1.2.2 Known history of: Sickle cell anemia, chronic bleeding, blood transfusion within past 120 days (excluding for chronic illness), or other blood dyscrasias Bone fracture not explained by trauma Allergy/sensitivity to FTC/TDF or its components 4.1.2.3 Fetus: known or suspected major congenital anomaly 4.1.2.4 Confirmed renal insufficiency, history of renal parenchymal disease, or known single kidney

40 PrEP Component Exclusion Criteria (cont.) 4.1.2.5 Current use of prohibited medications (protocol section 5.5) 4.1.2.6 Concurrent participation in a study of any biomedical HIV prevention intervention or investigational drug in an HIV vaccine study or microbicide study 4.1.2.7 Past participation in an HIV vaccine study 4.1.2.8 Currently taking a PrEP regimen from non-study sources 4.1.2.9 Any other condition/adverse social situation, per investigator discretion 4.1.2.10 Past participation in IMPAACT 2009 Former PK component participants NOT eligible!

Step 2 Inclusion Criteria: Cohort 2 Only 41

42 Step 2 Inclusion Criteria: Cohort 2 Only Cohort 2 maternal participants who subsequently choose to initiate PrEP complete Step Change Visits 1 and 2 (Section 6.2.3.2 and Appendix IIB) and must meet all of the following criteria in order to enter Cohort 2/Step 2 to initiate PrEP HIV Negative: Step Change Visit 1: by HIV RNA Step Change Visit 2: by HIV rapid and lack of acute HIV symptoms Protocol ref: 4.2.3.1 Regular access to cell phone that can receive AND send SMS Protocol ref: 4.2.3.5 Hepatitis B negative at Step Change Visit 1 Normal ( 90mL/min) estimated creatinine clearance (CrCl; Cockcroft-Gault formula) at previous assessment Negative or trace proteinuria (less than Grade 1) at Step Change Visit 1 Protocol ref: 4.2.3.2, 4.2.3.3 Willingness to take PrEP through 26 weeks postpartum 4.2.3.4 Protocol ref: 4.2.3.4

43 Infant Eligibility Infants enter the study at the same time their mother is enrolled. There are no set inclusion or exclusion criteria for infants.

44 Questions? Please raise your hand or type your questions into the chat box.

IMPAACT 2009: Informed Consent PrEP Comparison Component Protocol Version 3.0 with CM#1 Ashley Mayo, FHI 360 23 August 2021

46 Informed Consent/Assent Mothers of Legal Age: Mother must be willing/able to provide written informed consent for her and her infant’s participation. All sites must establish the SOPs that document the locally-applicable legal age of independent informed consent for research, noting whether this age differs for young women who are pregnant. Reference the DAIDS SCORE Manual for a full description of SOP requirements for enrolling minors. For Minors: Parental consent with participant assent OR Waiver of parental consent (i.e., minor maternal participant may provide written informed consent for her and her infant)

47 Use the annotate tool or the chat to answer: What approach your site will use to consenting minors? Parental Consent with Participant Assent: Waiver of parental consent:

48 Site-specific consent updates for minors Sites will adapt the consent forms to clarify for minor participants what information will and will not be shared with parents/guardians based on local regulations. Even under a consent/assent requirement, minors can consent independently to some procedures in the study depending on local laws; for example, minors may be allowed to consent independently to: Medical treatment, including STI and HIV treatment Contraceptive access and contraceptive advice and information, including emergency contraceptives Pregnancy testing and counseling

49 PrEP Comparison Component Informed Consent Types 1. Screening/Enrollment Consent for mother and baby participation Assent signature page (as needed) Optional procedure: rectal swab collection 2. Specimen Storage and Future Use Consent for mother and baby sample storage Includes specific consent for genetic testing 3. In-depth Interview Informed Consent Form For participants selected for IDIs Must be completed at screening, before any study specific procedures Completed at screening or entry visit Declining sample storage does not preclude participation Must be obtained prior to interview

50 Use the Chat Box or raise your hand: What informed consent support materials do you plan to use (e.g., visual aids, factsheets, sample tablets, or other materials?) How does your site assess comprehension? Study Overv iew

51 IC Documentation Coversheet may be used to document required elements (as outlined in IMPAACT MOP Section 8 and DAIDS SCORE Manual) All consents must be maintained in participant file Also document in a signed and dated chart note, specifically that informed consent was obtained before any study procedures were performed Informed consent and assent decisions will also be entered into eCRFs for mothers and infants Participants should be offered a signed copy of their ICF, if declined, provide alternate form of study contact information

52 Homework: IC Scenarios for discussion with your team 1. A participant provides informed consent for her and her infant at the Screening Visit. At the enrollment visit, the participant starts expressing some hesitations about being able to make it to the study clinic for visits as she’s recently gained new employment. How do you proceed?

53 Homework: IC Scenarios for discussion with your team 2. A 17-year-old mother is enrolled in the study by parental consent with participant assent. At her antepartum week 12 visit, she has recently celebrated her 18th birthday. She expresses that she doesn’t have time to reconsent and needs to leave the clinic in an hour. What do you do?

54 Homework: IC Scenarios for discussion with your team 3. A maternal participant experiences severe post-partum hemorrhage and dies shortly after giving birth to a healthy baby girl. The mother’s sister has taken on caring for the child and the father is unknown. The sister knows about the study and wants the baby to continue participation in order to receive the care and safety monitoring from the site. How do you proceed?

55 Questions? Please raise your hand or type your questions into the chat box.

IMPAACT 2009 PrEP Comparison Component Section 6 and Schedule of Evaluations Part 1 Emily Brown, FHI 360 23 Aug 2021

Protocol References 57 Section Title 6.0 Study Visits and Procedures 6.2 PrEP Comparison Component Appendices Schedules of Evaluations IIA - IIC

Pop Quiz 58 Using the Zoom annotation feature, please indicate which Appendix (right) holds the SoE for each group of participants (left). Cohort 1 Infant Participants Cohort 1 Maternal Participants Appendix IIA Cohort 2 Infant Participants Appendix IIB Cohort 2 Maternal Participants Cohort 2/Step 2 Maternal Participants Appendix IIC

59 Three Schedules of Evaluations

60 Additional Schedules of Evaluations

IMPAACT 2009 PrEP Comparison Component Screening Visits 61

Protocol References 62 Section Title 6.2.1 PrEP Comparison Component Maternal Screening 6.8 6.9 6.15 Appendix IIA Maternal Medical and Medication History Maternal Physical Examinations Fetal Ultrasound Schedule of Evaluations: Maternal PrEP Comparison Component Cohort 1 and Cohort 2/Step 2 Appendix IIB Schedule of Evaluations: Maternal PrEP Comparison Component Cohort 2

63 Section 6.2.1: Screening Visit Procedural Table

64 Key Operational Reminders for Screening Visits Screening may be initiated after written informed consent is obtained Screening procedures must be performed within 30 days prior to enrollment* Screening procedures may be performed on multiple days, including on the date of enrollment Screening procedures may be repeated, with the latest outcome used for eligibility determination * Except for HIV RNA test; HIV negative NAT test result, from a specimen collected within 14 days prior to enrollment, is required prior to Entry.

Pop Quiz #4 65 A mother’s baseline medical history is first recorded at the Screening Visit. True False

66 Where in the protocol can you find the required elements of the baseline medical history? Section 6.8

Pop Quiz #5 67 A complete maternal physical exam is required at the Screening Visit. True False

68 Where in the protocol can you find the required elements of the complete maternal physical exam? Section 6.9

Pop Quiz #6 69 Plasma should be stored for HIV drug resistance testing for all mothers who are screened, regardless of whether they enroll in the study. True False

Pop Quiz #6 70 Plasma should be stored for HIV drug resistance testing for all mothers who are screened, regardless of whether they#3 enroll in the study. See footnote in Appendix IIA and IIB: Store plasma for HIV drug resistance testing at all True visits EXCEPT screening 3 False

What are your questions? 71 Please raise your hand or type your questions into the chat box.

IMPAACT 2009 PrEP Comparison Component Entry Visits 72

Protocol References 73 Section Title 6.2.1.1 PrEP Comparison Component Maternal Enrollment Visit Appendix IIA Schedule of Evaluations: Maternal PrEP Comparison Component Cohort 1 and Cohort 2/Step 2 Appendix IIB Schedule of Evaluations: Maternal PrEP Comparison Component Cohort 2

Pop Quiz #7 74 A maternal participant who meets all other eligibility requirements can be enrolled as long as her first screening visit occurred when she was 32 weeks’ gestation. True False

Pop Quiz #7 75 A maternal participant who meets all other eligibility requirements can be enrolled as long as her first See protocol Sectionwhen 6.2.1.1: screening visit occurred she was 32 weeks’ gestation. ForTrue eligible women, enrollment must occur in time for study drug initiation prior to 32 False weeks of gestation. completed

76 Section 6.2.1: Enrollment Visit Procedural Table

77 Key operational reminders for Entry Visits All Entry Visit procedures are expected to be performed on the day of enrollment If a participant is found to be ineligible on the day of enrollment, enrollment must not occur The point of enrollment is taken to be the time when a participant has successfully been entered in the Study Enrollment System (SES). Day of Entry Day 0

78 Sequencing of procedures at the Entry Visit Procedures that may provide information relevant to eligibility (e.g., medical history, physical examination, HIV rapid test) should be performed first, prior to final eligibility determination Final eligibility determination and confirmation must precede enrollment Blood collection for baseline TFV-DP level must precede ingestion of first dose of study drug Prescribing must precede dispensing and administering of study drug

What are your questions? 79 Please raise your hand or type your questions into the chat box.

IMPAACT 2009 PrEP Comparison Component Review of additional study procedures 80

Social Harms Assessment and Reporting

Protocol References 82 Section Title 7.2 9.3.2 13.6 Safety-Related Data Collection Monitoring: Participant Safety Social Impacts Additional information on Social Harms can be found in Section 7.1 of the IMPAACT 2009 Manual of Procedures

Social Harms 83 Participants may experience social harms – non-medical adverse consequences – as a result of their participation in IMPAACT 2009, including as a result of their use of PrEP. For example, participants could experience difficulties in their personal relationships with partners, family members, and friends. They also could experience stigma or discrimination from family members and members of their community.

Social Harms 84 Social harms assessment will be done at every follow-up visit in the PrEP Comparison Component. All reported social harms will be source documented and entered into eCRFs (QLW10175).

Social Harms 85 Sites will develop a study-specific SOP to outline their operational plan for ensuring appropriate follow-up support and counseling, including referral to non-study resources, as necessary. Sites must confirm completion of this SOP as a requirement for site-specific study activation.

integrated Next Step Counseling iNSC 86

Protocol References 87 Section Title 5.3.2 Behavioral Counseling and Adherence Support, PrEP Comparison Component 6.2 Study Visits and Procedures, PrEP Comparison Component 6.5 PrEP Comparison Component – Interim Visit for Drug Level Feedback Appendix IIA Schedule of Evaluations: Maternal PrEP Comparison Component Cohort 1 and Cohort 2/Step 2 Appendix IIB Schedule of Evaluations: Maternal PrEP Comparison Component Cohort 2

iNSC 88 At all study visits, all maternal participants in both cohorts will receive iNSC The purpose of iNSC is to encourage exploration, problem solving, and skills building around non-biomedical strategies to prevent HIV and other STIs

targeted iNSC (t-iNSC) 89 t-iNSC is used to deliver drug concentration information for all participants who are taking PrEP (Cohort 1 and Cohort 2/Step 2) Study counselors will present TFV-DP results using zones (green, yellow, red) on the basis of concentration, pregnancy status, and weeks on PrEP Data from the PK Component of IMPAACT 2009 were used to create these zones, based on estimated frequency of PrEP use: 7 doses per week, 2-6 doses per week, and 2 doses per week Only counselors trained in t-iNSC should provide drug level feedback results

iNSC Training – 3 Upcoming Sessions 90 Session 1: Tuesday, 24 August (tomorrow) Session 2: Wednesday, 1 September Session 3: Wednesday, 8 September All sessions are scheduled for 2 hours, and will begin at 2:00pm CAT/ 3:00pm EAT

Qualitative In-Depth Interviews

Protocol References 92 Section Title 3.2.1 6.2.1.8 Qualitative Evaluation Design PrEP Comparison Component Maternal Qualitative In-Depth Interview Visit Appendix IX Sample In-depth Interview Informed Consent Form IDI Training Session scheduled for Thursday, 26 August at 2:00pm CAT/ 3:00pm EAT

93 Qualitative In-Depth Interviews Interviews will be conducted with 60 women, stratified into six groups: Group Adherent PrEP maternal participants Cohort 1 Cohort 2 Antepartum Postpartum 10 10 Non-adherent PrEP maternal participants 10 10 Maternal Participants who decline PrEP 10 10 IDI Scheduling: Currently pregnant: At or after Week 12 and prior to labor Postpartum: At Week 14 through to and including Week 26

94 Qualitative Management Team QMT Lead: Petina Musara QMT Investigator/Protocol Vice-Chair: K. Rivet Amico Protocol Co-Chairs: Ben Chi and Lynda Stranix-Chibanda QMT Epidemiologist: Deborah Kacanek QMT Data Managers: Benjamin Johnston and Mattie Bartlett QMT Clinical Trials Specialists: Ashley Mayo, Emily Brown, and Michael Whitton [email protected]

What are your questions? 95 Please raise your hand or type your questions into the chat box.