Clinical trial NCT02862171
Conditions: HIV Prevention
Sponsor: International Partnership for Microbicides, Inc.
Start date: 2016-07-12; Completion date: 2019-01-11
Enrollment: 941 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
A follow-on, open label trial to assess continued safety of and adherence to the Dapivirine(25mg) vaginal ring-004 in healthy, HIV-negative women

Detailed description:
Phase IIIb, multicenter follow-on open-label trial to evaluate the continued adherence to and safety of the DVR, inserted at monthly intervals by healthy, HIV negative women who had participated in the IPM 027 Phase III DVR trial. All women who participated in IPM 027 (NCT 01539226) and were HIV-negative at screening for IPM 032, were eligible.

Participants who provided written informed consent at screening were invited to undergo screening assessments for the trial. The Enrollment Visit had to occur within 45 days after the Screening Visit. Note: In the event that participation in IPM 027 was stopped prematurely and IPM 032 was activated at the RC, the IPM 027 Last Product Use Visit (LPUV) and the IPM 032 Screening and Enrollment Visits could be combined for participants who were eligible to enroll in IPM 032.

All participants received the DVR containing 25 mg dapivirine at the Enrollment Visit, and attended a visit at the RC, 1 month after enrollment. Following this visit, a participant could continue on a 3 monthly visit schedule, at the Investigator's discretion. Monthly visits could, however, be extended up to the first 3 months of participation. From then on, all participants needed to switch to a 3-monthly schedule. Once the 3-monthly trial visit schedule commenced, three rings were dispensed at each visit. One ring was self-inserted at the RC and two additional rings were dispensed for the participant to take home, or dispensing took place as arranged with the participant.

The protocol made provision for at least 12 months of DVR use (with the LPUV scheduled at Month 12), which could also have been extended. Participants could continue with ring use past Month 12 and the RCs could continue scheduling the 3-monthly visits as per the participant visit schedule. Exit Visits of participants who completed 12 months or more on the trial commenced in October 2017 and ended in January 2019. Participants who were still enrolled in the trial in October 2017 and those who had been enrolled at a later stage in the trial were scheduled to attend the Month 12 Visit, irrespective of their visit schedule assignments. Exit Visits were then scheduled as per protocol, ie, 1 to 2 months after the Month 12 Visit. Exit Visits were optional for participants who discontinued early from the trial.

Adherence assessments included analysis of dapivirine residual levels in returned used rings, correlation analysis of dapivirine residual levels with visual inspection of used rings, and self-reported acceptability and adherence.

The HIV-1 incidence and the occurrence of HIV-1 drug resistance were assessed using HIV rapid testing and genotyping, respectively.

Social and behavioral parameters were assessed qualitatively and quantitatively. Quantitative assessments included evaluation of the feasibility of 3-monthly follow-up visits and evaluation of the proportion of participants undergoing unscheduled HIV rapid tests (ie, in between the scheduled 3 monthly follow-up visits).

Safety assessments included adverse event (AE) reporting, safety laboratory assessments, pregnancy testing, physical examination, vital sign assessments, pelvic examination, sexually transmitted infection (STI) tests, cervical cytology, and assessments of social harms.

Throughout the trial, all participants received pre- and post-test HIV counseling, HIV/STI risk reduction counseling, and contraceptive, condom and vaginal ring adherence counseling.

Arms: arm 1: Dapivirine Vaginal Ring, 25 mg.Each participant will engage in the screening process for up to 45 days prior to enrolment and will use the monthly Dapivirine Vaginal Ring for a period of up to 12 months. IPM will have the option to extend this trial period.
Interventions: intervention 1: Dapivirine Vaginal Ring-004
Intervention descriptions: intervention 1: To assess the safety profile of the 25 mg Dapivirine Vaginal Ring-004, when inserted at monthly intervals, in an open-label trial

Protocol documents:
Prot_002.pdf: 
 
IPM 032 
Protocol 
 
CONFIDENTIAL 
CLIN-TEM-GEN-0001.00, 13Jan2016 
 
Page 1 of 1 
 
NCT02862171 
 
IPM 032 
 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF AND 
ADHERENCE TO THE DAPIVIRINE (25 mg) VAGINAL RING-004 IN HEALTHY, HIV-NEGATIVE 
WOMEN  
 
• 
Protocol Version 2.0 Amendment 1.0 dated 22 October 2015 
 


IPM 032 
 
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IPM 032 
 
Version 2.0 Amendment 1.0 
 
22 October 2015 
 
 
 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF AND 
ADHERENCE TO THE DAPIVIRINE (25 mg) VAGINAL RING-004 IN HEALTHY, 
HIV-NEGATIVE WOMEN 
 
 
 
 
Phase IIIb 
 
 
 
 
SPONSOR: 
International Partnership for Microbicides 
8401 Colesville Road, Suite 200 
Silver Spring, MD 20910 U.S.A. 
Phone: 1-301-608-2221 
Fax: 1-301-608-2241 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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SIGNATURE PAGE 
 
 
IPM 032 
 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF AND 
ADHERENCE TO THE DAPIVIRINE (25 mg) VAGINAL RING-004 IN HEALTHY, 
HIV-NEGATIVE WOMEN 
 
I have read this protocol and appendices and agree to conduct the trial as stipulated and 
in compliance with the principles of the World Medical Association Declaration of 
Helsinki, the International Conference on Harmonisation (ICH) Good Clinical Practice 
(GCP) guidelines, and all applicable regulations and guidelines. 
 
 
 
__________________________________   
__________________________ 
Investigator Signature 
 
 
 
Date 
 
 
__________________________________  
___________________________ 
Investigator Name (Printed)  
 
 
Research Centre Name 
 
 
 
On behalf of the International Partnership for Microbicides, I confirm that the sponsor will 
comply with all obligations as detailed in all applicable regulations and guidelines. I will 
ensure that the investigator is informed of all relevant information that becomes available 
during the conduct of this trial. 
 
 
____________________________________ 
_____________________________ 
Chief Medical Officer Signature 
 
 
Date 
 
 
Annaléne Nel, MBChB, PhD  
 
 
 
Chief Medical Officer Name (Printed) 
 
 
 
 


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TABLE OF CONTENTS 
 
ACRONYMS AND ABBREVIATIONS.............................................................................. 6 
1. 
Introduction ............................................................................................................ 18 
1.1. Background ..................................................................................................... 18 
1.2. Dapivirine Vaginal Ring ................................................................................... 18 
1.3. Nonclinical Studies .......................................................................................... 19 
1.4. Clinical Trials ................................................................................................... 20 
1.5. Rationale for Protocol IPM 032 ........................................................................ 23 
2. 
Trial Objectives ...................................................................................................... 23 
2.1. Trial Objectives ............................................................................................... 23 
2.2. Trial Endpoints and Assessments ................................................................... 24 
3. 
Overall Trial Design................................................................................................ 25 
3.1. Trial Design ..................................................................................................... 25 
3.2. Trial Duration .................................................................................................. 26 
3.3. Trial Population ............................................................................................... 26 
4. 
Trial Visits and Procedures .................................................................................... 27 
4.1. Screening Visit ................................................................................................ 27 
4.2. Enrolment Visit ................................................................................................ 28 
4.3. Trial Visits (monthly research centre visits for the first one to three months, and 
3-monthly research centre visits thereafter) .......................................................... 29 
4.4. Last Product Use Visit (LPUV) or Early Discontinuation Visit........................... 30 
4.5. Exit Visit .......................................................................................................... 32 
4.6. Unscheduled Visits .......................................................................................... 32 
4.7. Missed and Late Visits .................................................................................... 33 
4.8. Protocol Deviations ......................................................................................... 33 
4.9. Early Discontinuation Visits ............................................................................. 33 
4.10. Premature Discontinuation of the Trial ........................................................ 34 
5. 
Trial Procedure Details ........................................................................................... 34 
5.1. Informed Consent ............................................................................................ 34 
5.2. Comprehension Assessment Checklist ........................................................... 36 
5.3. HIV Counselling .............................................................................................. 36 
5.4. HIV Testing and Management ......................................................................... 36 
5.5. Contraceptive Counselling and Management of Contraception ....................... 40 
5.6. Pregnancy Testing and Management .............................................................. 41 


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5.7. Demographics and Medical History ................................................................. 42 
5.8. Physical Examination ...................................................................................... 42 
5.9. Pelvic Examination .......................................................................................... 42 
5.10. Laboratory testing for safety assessments and urine dipstick analysis ........ 42 
5.11. STI Testing and Management ..................................................................... 43 
5.12. Cervical Cytology ........................................................................................ 43 
5.13. Vaginal Ring Dispensing ............................................................................. 44 
5.14. Vaginal Ring Insertion and Ring Removal ................................................... 44 
5.15. Vaginal Ring Adherence Counselling .......................................................... 45 
5.16. Participant Questionnaire ............................................................................ 45 
5.17. Sample Storage and Analysis ..................................................................... 45 
5.18. Screening Identification (SCR-ID) and Participant Identification (PID) 
Numbers ............................................................................................................... 46 
5.19. Diary cards .................................................................................................. 46 
5.20. Reimbursement ........................................................................................... 46 
5.21. Participant Compensation ........................................................................... 46 
5.22. Participant Responsibility ............................................................................ 46 
5.23. Study Operations Manual (SOM) ................................................................ 47 
6. 
Investigational Product ........................................................................................... 47 
6.1. Investigational Product Composition ............................................................... 47 
6.2. Packaging and Labelling ................................................................................. 47 
6.3. Investigational Product Storage ....................................................................... 47 
6.4. Investigational Product Administration ............................................................. 48 
6.5. Investigational Product Expulsion or Loss ....................................................... 48 
6.6. Retrieval of Investigational Product ................................................................. 48 
6.7. Investigational Product (IP) Accountability....................................................... 49 
6.8. Concomitant Medications and Products .......................................................... 49 
7. 
Adverse Events ...................................................................................................... 49 
7.1. Definition ......................................................................................................... 49 
7.2. Assessment of Adverse Event Severity ........................................................... 50 
7.3. Relationship to Investigational Product ............................................................ 50 
7.4. Serious Adverse Event .................................................................................... 51 
7.5. Immediately Reportable Events ....................................................................... 53 
7.6. Safety Monitoring ............................................................................................ 53 
7.7. Data Handling at Research Centres ................................................................ 53 
7.8. Source Data Verification .................................................................................. 53 
8. 
Statistical Methods ................................................................................................. 54 
8.1. Trial Endpoints ................................................................................................ 54 
8.2. Primary Trial Hypotheses ................................................................................ 54 
8.3. Sample Size and Power Calculations .............................................................. 54 
8.4. Statistical Analyses ......................................................................................... 54 


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8.5. Data and Safety Monitoring Board .................................................................. 56 
8.6. Handling of Missing Data and Dropouts .......................................................... 56 
9. 
Investigator Requirements ..................................................................................... 56 
9.1. Trial Initiation ................................................................................................... 56 
9.2. Institutional Review Boards or Independent Ethics Committee Approval ......... 56 
9.3. Trial Monitoring and Audits .............................................................................. 57 
9.4. Case Report Forms (CRFs)............................................................................. 57 
9.5. Disclosure of Data ........................................................................................... 57 
9.6. Record Retention ............................................................................................ 57 
10. Ethical Considerations ........................................................................................... 58 
10.1. Ethical Review ............................................................................................ 58 
10.2. Reporting and Management of Social Harms related to trial participation .... 58 
10.3. Community Engagement ............................................................................. 58 
11. Publications ........................................................................................................... 59 
12. References ............................................................................................................ 60 
APPENDIX A: SCHEDULE OF PROCEDURES ............................................................ 61 
APPENDIX B: HIV TESTING ALGORITHM................................................................... 63 
APPENDIX C: VISIT SCHEDULE AND APPROXIMATE BLOOD VOLUMES ............... 68 
APPENDIX D: TRIAL DESIGN ...................................................................................... 69 
 
 
 


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ACRONYMS AND ABBREVIATIONS 
AE  
Adverse Event  
AIDS  
Acquired Immunodeficiency Syndrome  
ALT  
Alanine aminotransferase  
ARV  
Antiretroviral  
AST  
Aspartate aminotransferase  
AUC  
Area Under Plasma Concentration-time Curve  
BV 
Bacterial Vaginosis  
b.i.d. 
“bis in die”/twice a day 
ºC 
Degree Celsius 
CI 
Confidence Interval 
CNS 
Central Nervous System 
CRF  
Case Report Form  
CT 
Chlamydia Trachomatis 
DAIDS  
Division of Acquired Immunodeficiency Syndrome  
DAPY  
Di-aminopyrimidine  
DSMB  
Data and Safety Monitoring Board  
EC50  
50% Effective Inhibition Concentration 
FBC  
Full Blood Count  
FDA  
Food & Drug Administration (U.S.)  
GCP  
Good Clinical Practice  
HIV  
Human Immunodeficiency Virus  
Hu-SCID 
Humanized Severe Combined Immunodeficient  
ICF 
Informed Consent Form 
ICH  
International Conference on Harmonisation  
IEC  
Independent Ethics Committee  
IB 
Investigator’s Brochure 
IP 
Investigational Product 
IPM  
International Partnership for Microbicides  
IRB  
Institutional Review Board  
IRE  
Immediately Reportable Event  
ITT  
Intent-To-Treat 
LPUV 
Last Product Use Visit 
MedDRA 
Medical Dictionary for Regulatory Activities  
MTD  
Maximum Tolerated Dose  
MTN  
Microbicide Trials Network  
NAAT 
Nucleic Acid-Amplification Testing 
NG 
Neisseria Gonorrhoeae 
NNRTI  
Non-nucleoside Reverse Transcriptase Inhibitor  
NOAEL 
No Adverse Effect Level 
PCR  
Polymerase Chain Reaction  
PID  
Participant Identification  
PMTCT  
Prevention of Mother-to-Child Transmission of HIV  
PEP  
Post-Exposure Prophylaxis 
PT 
Preferred Term 
RNA  
Ribonucleic Acid  
RPR  
Rapid Plasma Reagin  
RT 
Reverse transcriptase 
SAE  
Serious Adverse Event  
SAP  
Statistical Analysis Plan  


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SCR-ID 
Screening Identification  
SOC 
System Organ Class 
SOM 
Study Operations Manual 
SOP 
Standard Operating Procedure 
STI  
Sexually Transmitted Infection 
TEAE  
Treatment Emergent Adverse Event  
TPHA  
Treponema Pallidum Haemagglutination Test  
TPPA  
Treponema Pallidum Particle Agglutination Assay  
TV 
Trichomonas Vaginalis 
UNAIDS  
Joint United Nations Programme on HIV/AIDS  
WHO  
World Health Organization 
 
 
 
 
 
 


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PROTOCOL SYNOPSIS 
IPM 032 
 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF AND 
ADHERENCE TO THE DAPIVIRINE (25 mg) VAGINAL RING-004 IN HEALTHY, 
HIV-NEGATIVE WOMEN 
 
BACKGROUND:  
The Phase III clinical program of Dapivirine Vaginal Ring-004, 
containing 25 mg of dapivirine, consists of the MTN-020 and 
IPM 027 clinical trials. These trials are conducted in South Africa, 
Uganda, Zimbabwe and Malawi, to assess the safety and efficacy 
of the Dapivirine Vaginal Ring-004 in preventing the acquisition of 
HIV-1 infection through male to female transmission in healthy, 
HIV-negative women. 
 
IPM 032, a Phase IIIb follow-on trial to IPM 027, has been 
designed as an open-label clinical trial to collect additional safety 
data and establish adherence to ring use of the Dapivirine (25 mg) 
Vaginal Ring-004 in healthy, HIV-negative women with monthly (at 
least one to a maximum of three months) followed by 3-monthly 
research centre follow-up visits over 12 months.  The safety results 
and the level of efficacy observed in IPM 027 and MTN-020 will be 
communicated to the relevant local and international regulatory 
authorities, IRBs/IECs, community representatives, participants 
and key stakeholders, as appropriate, before activation of IPM 
032. 
 
IPM 032 will be an open-label clinical trial to assess the continued 
safety of and adherence to the Dapivirine Vaginal Ring-004, 
inserted monthly in healthy, HIV-negative women. 
 
OBJECTIVES: 
The Primary Trial Objectives are: 
 
1. To assess the safety profile of the 25 mg Dapivirine Vaginal 
Ring-004, when inserted at monthly intervals, in an open-label 
trial  
2. To assess adherence to the use of the 25 mg Dapivirine 
Vaginal Ring-004 inserted at monthly intervals, in an open-
label trial  
 
The Secondary Trial Objectives are: 
 
1. To assess the incidence of HIV-1 seroconversion 
2. To assess the frequency of HIV-1 drug resistance in women 
who acquire HIV-1 infection 
 
 
 
 
 
 
 


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The Exploratory Trial Objectives are: 
 
1. 
To assess the feasibility of 3-monthly follow-up visits, as a 
possible schedule for post-licensure vaginal ring clinical 
follow-up 
2. 
To explore the correlation between drug concentrations and 
results from the visual inspection of the returned vaginal rings 
by research staff between the monthly and 3-monthly research 
centre follow-up schedules 
3. 
To determine the proportion of participants electing to undergo 
HIV rapid tests at the research centres between scheduled 3-
monthly visits 
 
 
ENDPOINTS AND ASSESSMENTS:  
 
 
The primary endpoints are: 
 
1. 
Safety  
• 
All Adverse Events (AEs) assessed by the investigator to 
be related to the Dapivirine Vaginal Ring-004 
• 
All Grade 3 and 4 AEs 
• 
All Serious Adverse Events (SAEs) 
 
2. 
Adherence 
• 
Residual amounts of dapivirine in returned rings; and/or 
dapivirine concentrations in plasma and/or dapivirine 
concentrations in vaginal fluid  
 
 
The primary endpoints will be assessed through: 
 
1. 
Safety  
• 
All product-related AEs, Grade 3 or 4 AEs, SAEs, physical 
examination, 
gynaecological 
assessments, 
including 
pelvic/speculum examination, laboratory tests and other 
indicated investigations 
 
2. 
Adherence 
• 
Determined dapivirine residual amounts in returned used 
vaginal rings and/or 
• 
Measured concentrations of dapivirine in plasma and/or 
• 
Measured concentrations of dapivirine in vaginal fluids  
 
 
 
 


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The secondary endpoints are: 
 
• 
The HIV-1 seroconversion rate per 100 woman-years of 
product use at the end of the vaginal ring use period 
• 
HIV-1 drug resistance mutations among participants who 
acquire HIV-1 infection 
 
 
The secondary endpoints will be assessed through: 
 
• 
Rapid and specialised laboratory testing according to a 
pre-specified HIV testing algorithm 
• 
Viral genotype resistance testing methods 
 
  
 
The exploratory endpoints are: 
 
• 
Feasibility of 3-monthly clinical follow-up schedule 
• 
Dapivirine residual amounts in returned used vaginal rings 
and/or dapivirine concentrations in blood and/or vaginal 
fluid in correlation with results from the visual inspection 
of the returned used vaginal rings by research staff 
• 
Proportion of participants opting for HIV rapid tests at the 
research centre between scheduled 3-monthly research 
centre follow-up visits 
 
 
The exploratory endpoints will be assessed through: 
 
• 
Participant report of feasibility regarding a 3-monthly 
clinical follow-up schedule (Participant Questionnaire)    
• 
Number of women opting not to receive two additional 
rings at the 3-monthly visits  
• 
Proportion of returned rings (used and unused) during the 
3-monthly clinical follow-up schedule 
• 
Dapivirine residual amounts in returned used vaginal rings 
and/or dapivirine concentrations in blood and/or vaginal 
fluid 
• 
Visual inspection of the returned used vaginal rings by 
research centre staff 
• 
Number of participants undergoing HIV rapid tests at the 
research centre between scheduled 3-monthly research 
centre follow-up visits 
 
TRIAL DESIGN:  
IPM 032 is a Phase IIIb, multi-centre follow-on open-label trial to 
evaluate the continued adherence to and safety of the Dapivirine 
Vaginal Ring-004 inserted at monthly intervals in healthy, HIV-


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negative women who have participated in the IPM 027 Phase III 
Dapivirine Vaginal Ring-004 trial. All women who have participated 
in IPM 027 and are HIV-negative at screening for IPM 032 will be 
eligible. An estimate of approximately 1400 participants will be 
enrolled.    
 
All participants will attend a research centre follow-up visit one 
month after enrolment.  Following this visit, at investigator’s 
discretion, a participant can continue on a 3-monthly visit 
schedule.   Monthly visits may however be extended up to the first 
three months of participation. Once the 3-monthly trial visit 
schedule commences, three rings will be dispensed to the 
participant.  One ring will be self-inserted at the research centre 
and two additional rings will be dispensed for the participant to 
take home, or dispensing will take place as arranged with the 
participant.  
 
 
  
TRIAL DURATION:  Each participant will engage in the screening process for up to 45 
days prior to enrolment and will use the Dapivirine Vaginal Ring-
004 for a period of up to 12 months. IPM will have the option to 
extend this trial period. Accrual will take place over approximately 
6 months and those participants who are enrolled more than 6 
months after the onset of the study site’s accrual period may have 
a shortened follow-up period. 
 
Each participant will have an exit visit 1-2 months after ring 
discontinuation, to assess safety and identify HIV seroconversions 
after product discontinuation.  
 
POPULATION AND SAMPLE SIZE: 
 
Approximately 1400 HIV-negative women who have participated in 
the IPM 027 Phase III Dapivirine Vaginal Ring-004 trial, who 
understand the trial, and can provide informed consent, are 
expected to enrol in this open-label trial.   
 
INCLUSION CRITERIA: 
Women must meet all of the following criteria to be eligible for trial 
enrolment: 
 
1. 
Previously enrolled in the IPM 027 trial  
2. 
Available for all visits and consent to follow all procedures 
scheduled for the trial 
3. 
Using an effective method of contraception at the 
Enrolment Visit, and intending to use an effective 
contraceptive method for the duration of trial participation, 
unless post-menopausal with no history of menses for 
one year prior to screening  
4. 
HIV-negative as determined by the HIV algorithm applied 
at Screening/Pre-Enrolment 


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5. 
Willing to refrain from participation in another research 
trial using drugs, vaccines, medical devices and 
microbicides for the duration of the IPM 032 trial 
6. 
Willing to provide adequate locator information for trial 
retention purposes and be reachable per local standard 
procedures (e.g. by home visit or telephone; or via family 
or close neighbour contacts); confidentiality to be 
maintained 
 
EXCLUSION CRITERIA: 
Women who meet any of the following criteria are NOT eligible to 
enroll in the trial: 
 
1. 
Investigational product use permanently discontinued in 
response to an AE (where the AE was considered related 
to investigational product) or safety-related concern while 
taking part in the IPM 027 trial  
2. 
Participant self-report of taking post-exposure prophylaxis 
(PEP) within ≤ 2 months at Screening Visit 
Note: Participants may be enrolled after completing the 
PEP regimen and a negative HIV test was documented at 
least 2 months prior to screening for IPM 032 
3. 
Currently pregnant, intends to become pregnant, or 
currently breast-feeding 
4. 
Known drug abuse or alcohol dependence in the 12 
months prior to screening 
5. 
Participated in another research trial (other than IPM 027) 
using drugs, medical devices, microbicides or oral pre-
exposure prophylaxis agents within 30 days prior to 
screening 
6. 
Any new illness or condition(s), chronic condition(s) or 
abnormal laboratory finding(s) that, in the opinion of the 
investigator, might put the participant at risk, or interfere 
with the trial objectives or the participant’s adherence to 
trial requirements 
 
METHODS: 
Screening Visit:  
 
Potential participants who are HIV-negative, who participated in 
IPM 027 and who provide informed consent will be invited to 
screen for the trial and to enrol in the open-label follow-on study. 
After informed consent is obtained, a SCR-ID number will be 
assigned to each potential participant for identification purposes 
and the potential participant will be screened to assess eligibility 
for the study. A comprehension checklist will be used to support 
the informed consent process.   
 
 At screening, potential participants will provide information on 
inclusion and exclusion criteria, including locator and basic 


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menses information, demographic information, and medical and 
concomitant medication history.  Each potential participant will 
receive a general physical examination and pelvic examination.  
 
All potential participants will be provided with HIV/STI risk-
reduction counselling (including provision of male condoms, 
should 
participants 
wish 
to 
receive 
them), 
contraceptive 
counselling 
and 
HIV 
pre- 
and 
post-test 
counselling. 
Contraceptives will be provided if necessary, as well as treatment 
and/or referral for sexually transmitted infections (STIs) and other 
findings as necessary. Safety laboratory assessments, urine 
dipstick analysis (microscopy only if clinically indicated), cervical 
sample collection for cytology and testing for pregnancy, HIV, 
STIs, and syphilis will be performed. Blood samples for HIV-1 
RNA PCR and HIV viral genotype resistance testing will be 
collected and stored for retrospective testing subsequent to a 
confirmed HIV-1 seroconversion. 
 
 
Enrolment Visit: 
 
At the Enrolment Visit, potential participants will provide 
information on inclusion and exclusion criteria, including locator 
and basic menses information, and medical and concomitant 
medication history.  AEs (post-enrolment) and the occurrence of 
possible social harms will be assessed. 
 
All potential participants will be provided with HIV/STI risk-
reduction counselling (including provision of male condoms, 
should 
participants 
wish 
to 
receive 
them), 
contraceptive 
counselling and provision of contraceptives (if necessary), HIV 
pre- and post-test counselling and vaginal ring adherence 
counselling. Participants will be provided with feedback on the 
IPM 027 and MTN-020 trial results. Diary cards will be issued with 
instructions for completion. Testing for pregnancy and HIV will be 
performed. Blood samples will be collected for storage, and HIV-1 
RNA PCR and HIV viral genotype resistance testing will be 
performed 
retrospectively 
subsequent 
to 
confirmed 
HIV-1 
seroconversion.  
 
Eligible women will be assigned a unique PID number. Each  
participant will be provided with vaginal ring use and storage  
instructions and instructed to self-insert a newly dispensed vaginal  
ring.  
 
Trial Visits:  
All participants will provide information on concomitant medication, 
locator details and menses. Participants will receive pre- and post-
test HIV counselling; HIV/STI risk reduction counselling; vaginal 
ring adherence counselling; HIV rapid testing and pregnancy 
testing. Male condoms will be provided at all visits, should 
participants wish to receive them, as part of HIV/STI risk reduction 


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counselling. Contraceptive counselling and contraceptives (if 
needed) will be provided at all visits. Possible occurrence of social 
harms will be assessed during research centre visits.   
 
Blood samples will be collected for storage at each trial visit and 
will be tested retrospectively by HIV-1 RNA PCR and HIV viral 
genotype resistance testing subsequent to confirmed HIV 
seroconversion.  At the point of HIV seroconversion, vaginal ring 
use will be discontinued, and in addition, blood samples for viral 
genotype resistance testing will be collected at the scheduled exit 
visit, 1-2 months following seroconversion.  
 
Blood and vaginal fluid samples will be collected for possible 
measurement of dapivirine concentrations. Returned rings will be 
visually inspected by research centre staff and may also be 
analysed for residual amounts of dapivirine. 
 
Returned diary cards will be reviewed and new diary cards issued 
to participants as applicable. Each participant will be asked to 
complete a Participant Questionnaire at every trial visit.  AEs will 
be assessed at all visits post-enrolment. In addition, if clinically 
indicated, safety laboratory assessments, urine dipstick analysis 
(microscopy only if clinically indicated), pelvic examinations, 
cervical sample collection for cytology, physical examinations and 
STI tests will be performed. Treatment and/or referral for STIs and 
other findings may be performed, if required.    
 
At each trial visit, participants will return used vaginal rings and 
each participant will be instructed to self-insert a newly-dispensed 
vaginal ring and be provided with vaginal ring use and storage 
instructions. Two additional rings will be dispensed once 
participants commence with the 3-monthly trial visit schedule,  
which the participants should self-insert at monthly intervals, at 
home, until the next Trial Visit. Participants who prefer not to have 
additional vaginal rings in their possession may also choose to 
return and to collect the vaginal rings from the research centre at 
time intervals suitable to them, providing a new ring is inserted 
monthly. HIV rapid tests will be offered to participants during these 
interim visits. 
 
If a participant is unable to attend the next scheduled visit, the 
investigator or designee could dispense additional ring(s) on a 
case-by-case basis. All such circumstances must be documented 
fully by the investigator or designee as described in the IPM 032 
Study Operations Manual (SOM). If a participant requires an 
additional ring at a time other than when they are scheduled to 
receive one, they will be required to attend the clinic for an interim 
visit. 
 
 
 


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Last product use visit (LPUV):   
At the last product use visit, participants will return any 
used/unused rings; report any medical problems, social harms and 
concomitant medications since the last visit; provide locator and 
basic menses information; receive pre- and post-test HIV 
counselling, contraceptive counselling and HIV/STI risk-reduction 
counselling (including provision of male condoms, should 
participants wish to receive them); undergo a physical examination 
as well as a pelvic examination; be tested for STIs, pregnancy and 
HIV; and may undergo safety laboratory assessments,  urine 
dipstick analysis (microscopy only if clinically indicated) and 
cervical sample collection for cytology (if no result is evident within 
the previous year, or abnormal at last cervical cytology).  
Contraception and STI treatment will be provided or participants 
will be referred, if needed.   Blood samples will be collected for 
storage, and will be tested retrospectively by HIV-1 RNA PCR and 
HIV viral genotype resistance testing subsequent to confirmed HIV 
seroconversion. Blood and vaginal fluid samples may be collected 
for measurement of dapivirine concentrations. Returned rings will 
be visually inspected by research centre staff and may also be 
analysed for residual amounts of dapivirine. Returned diary cards 
will be reviewed. Participants will be asked to complete a 
Participant Questionnaire. 
 
Exit visit - 1-2 months after ring discontinuation:  
On the day of the scheduled exit visit, participants will return to the 
research centre to receive results from their STI testing and safety 
laboratory assessments performed at the last product use visit, if 
applicable, and receive treatment or referral as needed. AEs, 
concomitant medications and possible social harms will be 
recorded at this visit. 
 
Participants will receive pre- and post-test counselling for HIV and 
undergo HIV testing. HIV/STI risk reduction counselling (including 
provision of male condoms, should they wish to receive them) and 
contraceptive counselling will also be provided at the exit visit. 
Contraception and STI treatment will be provided or the participant 
will be referred, if needed. The following procedures are not 
required, but may be conducted if clinically indicated: physical and 
pelvic examination, cervicovaginal sample collection for STI 
testing, provision of treatment and/or referral for STIs and other 
findings, laboratory testing for safety assessments, urine dipstick 
analysis (microscopy only if clinically indicated) and cervical 
sample collection for cytology (if no result is evident within the 
previous year, or abnormal at last cervical cytology). 
Blood samples will be collected for storage, and will be tested 
retrospectively by HIV-1 RNA PCR and HIV viral genotype 
resistance testing subsequent to confirmed HIV seroconversion. 
 
Participants will then be considered to have completed trial 
participation. 


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STATISTICAL CONSIDERATIONS: 
Sample Size:  
This is an open-label, follow-on trial to IPM 027 to evaluate the 
safety of and adherence to Dapivirine Vaginal Ring-004, inserted 
at monthly intervals in healthy, HIV-negative women who have 
participated in the IPM 027 trial. No formal sample size or power 
calculations have thus been performed. 
 
It is expected that approximately 70% of the participants enrolled 
in IPM 027 will participate in this trial. Therefore, a total sample 
size of approximately 1400 HIV-negative women is anticipated.  
 
Statistical Analyses:  
The primary analysis will focus on safety as well as adherence 
assessments, performed under the intent-to-treat (ITT) principle. 
As it is possible that the inclusion of non-adherent participants or 
participants who discontinued from ring use may artificially lower 
the rates of safety outcomes, additional analyses will be 
conducted on the per-protocol population, which will include only 
participants who were adherent to the protocol. 
 
A descriptive analysis of all AEs will be presented in tables and 
listings. AEs will be summarised by MedDRA System Organ Class 
(SOC) and Preferred Term (PT). The proportion of participants 
experiencing adverse events, including the proportion of 
participants experiencing product-related adverse events, Grade 3 
or 4 AEs, or SAEs, will be determined, and presented with 
corresponding 95% confidence intervals (CIs).  
 
Residual levels of dapivirine in returned rings, and/or plasma 
and/or vaginal fluid concentrations of dapivirine will be used as 
measures of adherence to ring use. The data will be listed, 
summarised and presented graphically. Participants will be 
categorized as either adherent or non-adherent, based on these 
measures. The ring residual levels and/or plasma and/or vaginal 
fluid concentrations of dapivirine associated with non-adherence 
will be informed by the results from IPM 027, and will be described 
in detail in the SAP, which will be finalised prior to final database 
lock.  The correlation between the amount of residual dapivirine in 
the used rings and the corresponding plasma and/or vaginal fluid 
levels of dapivirine will be explored graphically and summarised 
descriptively.  
 
For the secondary analysis, the number of HIV-1 seroconversions, 
the incidence density rate of HIV-1 seroconversion, i.e. HIV-1 
seroconversion rate per 100 woman-years of product use at the 
end of the ring use period, as well as a 95% confidence interval for 
the HIV-1 seroconversion rate per 100 woman-years based on the 
normal approximation of the Poisson distribution will be presented 
for each research centre and overall. Kaplan-Meier curves will 
also be presented, stratified by research centre. The analysis of 


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HIV-1 drug resistance will be primarily descriptive in nature, and 
will depend on the pattern of resistance mutations observed in the 
HIV-1 seroconverters.  A frequency tabulation of individual 
resistance mutations associated with the various classes of 
antiretrovirals, e.g. Protease Inhibitors, Nucleoside Reverse 
Transcriptase 
Inhibitors 
and 
Non-nucleoside 
Reverse 
Transcriptase Inhibitors, will be produced. The proportion of HIV-1 
seroconverters with at least one HIV-1 drug resistant mutation will 
be presented, with the corresponding 95% CI.  
 
Appropriate statistical analyses of the exploratory endpoints will be 
performed. 
 
 
 
 
Full details of the planned statistical analyses will be provided in a  
 
 
 
Statistical Analysis Plan (SAP) that will be finalised before final  
 
 
 
database lock. 
 
 
 
 
 
 


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1. Introduction 
1.1. Background 
Women continue to be affected disproportionately by HIV in sub-Saharan Africa, where 
they account for 58% of people living with HIV1. It is estimated that every hour, 50 young 
women are newly infected with HIV2. Unprotected heterosexual intercourse is currently 
the leading mode of HIV acquisition among women. Correct and consistent use of latex 
condoms is one proven method of preventing HIV acquisition. However, many women 
are unable to negotiate condom use with their partners. Most current HIV prevention 
methods require the consent (as well as some action or behaviour change) of the male 
partner3. Therefore, the ongoing development of safe and effective HIV prevention 
technologies that can be made easily accessible to developing countries remains a 
public health priority.  
 
Developing HIV prevention options that women can use therefore remains a global 
challenge. Antiretroviral (ARV) approaches to prevention have the potential to transform 
the response to the HIV/AIDS pandemic. For women, further research is needed on 
microbicides that contain different ARV compounds in different formulations and dosing 
strategies, in order to provide various options for HIV prevention. Vaginal microbicides, 
which are self-initiated, could offer women a critically needed new tool to prevent HIV, 
especially for those women who are not able to negotiate mutual monogamy or condom 
use4. ARV-based microbicides can be formulated in a number of dosage forms that 
allow them to be used in a variety of ways, such as around the time of sex, or daily or 
monthly, independent of sexual activity.  
 
In order for a microbicide to be most effective, it is essential that it is used correctly and 
consistently, and is acceptable to women and their male partners. A product used 
independently of sexual intercourse could be more convenient for women and provide 
long-term protection during anticipated and unanticipated sexual intercourse. Vaginal 
rings that need monthly replacement may therefore have benefits. The Dapivirine 
Vaginal Ring-004 is currently in Phase III clinical development.   
 
1.2. Dapivirine Vaginal Ring 
1.2.1. Dapivirine 
Dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is a di-amino-
pyrimidine 
(DAPY) 
derivative 
with 
the 
chemical 
name 
4-[[4-[(2,4,6-
trimethylphenyl)amino]-2-pyrimidinyl]amino] benzonitrile. NNRTIs bind directly to the HIV 
reverse transcriptase (RT) enzyme, preventing viral replication. Dapivirine was originally 
developed by Janssen Research and Development (formerly Tibotec Pharmaceuticals) 
as an oral antiretroviral compound and was tested in Phase I and II clinical trials in more 
than 200 participants. Although first conceived as an oral therapeutic, dapivirine is a 
promising candidate for development as a topical microbicide due to its proven in vitro 
and in vivo efficacy and favourable safety profile as well as its physical and chemical 
properties. Dapivirine has potent activity against wild-type HIV-1 strains and strains 
harbouring different resistance-inducing mutations. Dapivirine’s antiretroviral profile is 
superior to that of earlier NNRTI class compounds such as nevirapine, delavirdine, and 
efavirenz. In vitro tests have shown that dapivirine is inactive against HIV-2 and has no 
efficacy against common sexually transmitted infections. Dapivirine is therefore not 
intended to protect against HIV-2 or other sexually transmitted infections, nor does it 
have any contraceptive properties. 


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1.2.2. Formulation of a Silicone Elastomer Matrix ring containing 25 mg of  
 Dapivirine 
The dapivirine silicone elastomer vaginal matrix ring (Ring-004) is an off-white flexible 
ring containing 25 mg of dapivirine dispersed in a platinum-catalysed silicone matrix. The 
dimensions of the ring are 56 mm (outer diameter) and 7.7 mm (cross-sectional 
diameter). Details regarding the formulation and dimensions are provided in the 
Dapivirine Vaginal Ring-004 Investigator’s Brochure (IB)5. The dapivirine vaginal ring is 
designed to provide sustained release of dapivirine for a minimum of one month. 
 
1.3. Nonclinical Studies 
The potential of dapivirine as a microbicide for prevention of sexual transmission of HIV 
has been assessed in a variety of in vitro, ex vivo and in vivo models.  Furthermore, a 
comprehensive program of preclinical studies was used to evaluate the toxicity of 
dapivirine. The studies are described in the IB5. 
 
Virology: 
The activity of dapivirine against wild-type HIV-1, African isolates of HIV-1 (including 
subtype C virus), and a panel of NNRTI-resistant viruses has been established using in 
vitro models, with EC50 values ranging from 0.3 ng/mL (0.9 nM) against laboratory 
isolates to < 33 ng/mL (< 100 nM) for HIV-1 isolates encoding one or more known 
NNRTI resistance mutations. The anti-HIV activity was also confirmed in an ex vivo 
model of human cervical explant cultures and in an in vivo humanized severe combined 
immunodeficient (hu-SCID) mouse model. 
 
Nonclinical safety pharmacology: 
In a series of preclinical safety pharmacology studies, dapivirine was generally devoid of 
adverse effects on overt behaviour, reflexes and other body functions. Although safety 
pharmacology studies revealed no cardiovascular effects, there was evidence of an 
increase in QT interval during the 4- and 6-month oral toxicity study in dogs. However, 
this was only seen at ≥ 30 mg/kg/day, at which Cmax and AUC values were respectively 
more than 3800 and 2500 times the values achieved in women following use of the 
Dapivirine Vaginal Ring-004. 
 
Nonclinical pharmacokinetics:  
Systemic exposure to dapivirine was low following vaginal administration of dapivirine 
gels to rabbits. Much higher systemic exposures were obtained in single dose oral and 
subcutaneous toxicity studies in mice and rats, and in repeat dose oral toxicity studies in 
rats, dogs and monkeys. The free fraction of dapivirine in plasma was 0.19-0.34% in the 
male rat, 0.18-0.39% in the female rat, 0.21–0.22% in the dog and 0.15% in man. In rats, 
tissue to plasma AUC0-24 ratios following a single oral dose were 11 in liver, 7-8 in lung, 
kidney and adrenals, about 4 in spleen and lymph nodes, and 2-3 in brain, heart and 
muscle. Plasma/tissue equilibrium was rapid, and there was no undue retention of 
dapivirine in tissues.  
 
For virtually all tissues, maximal concentrations after vaginal dosing were < 1% of those 
after oral dosing. Preliminary metabolism studies demonstrated the presence of free and 
conjugated metabolites in rats, dogs, monkeys and humans, but the molecular structures 
have not been elucidated. There was evidence of extensive cytochrome P450 


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(particularly CYP3A4) mediated metabolism. 
 
Nonclinical toxicology:  
Dapivirine has been investigated in single and repeat dose toxicity studies, in a range of 
reproductive toxicity and mutagenicity studies, and in a carcinogenicity study. In vaginal 
studies in rabbits there were no significant local or systemic findings following repeat 
administration at up to 20 mg/mL for 14 days, up to 5 mg/mL for 13 weeks or up to 2 
mg/mL for 39 weeks, or in reproductive toxicity studies in rats and rabbits performed at 
concentrations up to 2 mg/mL (0.2%). In a 13-week study in sheep using Ring-004, there 
was no evidence of local or systemic toxicity. 
 
The no adverse effect level (NOAEL) in rats and dogs following oral administration was 
20 mg/kg/day. At higher dose levels, hepatotoxicity was observed in dogs and slight 
hematological and clinical chemistry changes were observed in rats. The NOAEL in oral 
reproductive toxicity studies in the rat was also 20 mg/kg/day, whereas in the rabbit no 
effects were seen at dosages up to 90 mg/kg/day. Dapivirine was considered to be non-
genotoxic. In the guinea pig, dapivirine (2 mg/mL) did not demonstrate any potential to 
cause contact sensitization. No treatment-related neoplastic or non-neoplastic findings 
were seen in a vaginal carcinogenicity study in rats at concentrations up to 5 mg/mL. 
 
1.4. Clinical Trials 
Multiple clinical trials have evaluated the safety of dapivirine in different formulations. 
Below is a summary of the data collected through these studies. More detailed 
information is available in the Dapivirine Vaginal Ring-004 IB5.  
 
Across all clinical trials with multiple ring configurations in healthy participants, the 
dapivirine vaginal ring was generally safe and well tolerated. No drug-related serious 
adverse events (SAEs) have been reported to date and no trials were stopped for safety 
reasons. Three Grade 3 SAEs (polytrauma event of thoracic vertebral fractures in IPM 
034, fracture of the right acetabulum in IPM 028 and tonsillitis in IPM 015), were reported 
for three participants who used the Dapivirine Vaginal Ring-004); all three events were 
regarded by the Investigator as unrelated to ring use. Six non-ring related SAEs were 
experienced by five participants using placebo rings in two Ring-004 trials (IPM 015 and 
IPM 024). One participant was discontinued from the Dapivirine Vaginal Ring-004 due to 
an investigational product-related adverse event (generalized pruritus) in IPM 013. 
 
1.4.1. Phase I and II 
To date, 27 Phase I and Phase I/II clinical trials of dapivirine have been completed: 8 
trials of dapivirine vaginal rings in 469 participants (298 using dapivirine rings and 183 
using placebo rings); 8 trials of dapivirine vaginal gel in 774 participants (491 using 
dapivirine gel and 283 using placebo gel); and 11 trials of oral dapivirine in which a total 
of 211 participants used oral dapivirine. Two Phase I clinical trials that evaluated a 
vaginal film formulation of dapivirine in 71 women have been conducted.  In addition, 
one Phase I clinical trial in male participants to assess the safety and tolerability of a 
dapivirine vaginal gel, following multiple topical penile exposures, was conducted in 48 
healthy, HIV-negative, adult males, 24 of whom were circumcised and 24 uncircumcised 
(MTN-012/IPM 010). The dapivirine gel formulation was well tolerated by the 
participants. No SAEs or discontinuations due to TEAEs were reported during this trial. 
 


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Based on information in the current IB5, across all completed Dapivirine Ring-004 trials 
(IPM 024, IPM 013, IPM 015, IPM 028 and IPM 034), the most commonly occurring 
TEAEs that were documented in at least 5% of participants in dapivirine versus 
placebo treated participants (n=259 using dapivirine rings and n=160 using placebo 
rings, respectively) were metrorrhagia (29.7% vs 24.4%), headache (15.1% vs 11.9%), 
gynaecological chlamydia infection (8.5% vs 13.4%), vaginal candidiasis (8.1% vs 7.5%), 
urinary tract infection (6.9% vs 8.8%), vaginal discharge (6.6% vs 6.3%), upper 
respiratory tract infection (5.8% vs 10.0%) and lower abdominal pain (5.4% vs 5.0%). 
 
 
Oral Dapivirine 
There have been 11 oral administration trials in which a total of 211 participants have 
been dosed with dapivirine. The maximum tolerated dose (MTD) established was 350 
mg for a single dose, and for multiple doses, 300 mg b.i.d. for 14 days. There were no 
deaths during the clinical trials of oral dapivirine, and no trials were stopped for safety 
reasons. A total of 10 participants stopped dapivirine treatment prior to trial completion 
for safety reasons, 6 of whom stopped due to a clear dose-dependent increase in central 
nervous system (CNS) and gastrointestinal TEAEs, thereby establishing the MTD at 300 
mg b.i.d. These TEAEs resolved within 1-2 days after discontinuation of use of oral 
dapivirine.  
 
Adverse events documented in 5 or more participants (> 2%) after oral exposure to 
dapivirine were headache, dizziness, nausea, diarrhoea, fatigue, tremor, somnolence, 
flatulence, and vomiting. Most (≥ 80%) of these TEAEs were Grade 1 or 2 (mild or 
moderate) and most (≥ 80%) were considered to be related to dapivirine. Grade 3 
(severe) TEAEs included headache, dizziness, injury, nausea, tremor, paraesthesia, 
disturbance in attention, abrasion, AST increased, ALT increased, polyuria, fever, 
diarrhoea, and vomiting. The increases in AST and ALT were transient and the Grade 3 
increases in AST and ALT occurred in a single participant who received 50 mg oral 
dapivirine as a twice daily dose.  
 
1.4.2. Phase III  
The Phase III clinical program of the dapivirine vaginal ring, containing 25 mg of 
dapivirine (Ring-004), consists of the MTN-020 and IPM 027 clinical trials. These trials 
are conducted in South Africa, Uganda, Zimbabwe and Malawi, to assess the safety and 
efficacy of the Dapivirine Vaginal Ring-004 in preventing the acquisition of HIV-1 
infection through male to female transmission in healthy, HIV-negative women.  
 
IPM 027 is a double-blind, multicentre, placebo-controlled trial that has been designed to 
assess the safety and efficacy of the Dapivirine Vaginal Ring-004, inserted once every 4 
weeks over a period of 24 months, in healthy, sexually active HIV-negative women, 18 to 
45 years of age, when compared to a placebo vaginal ring. It is conducted at 7 research 
centres, six in South Africa and one in Uganda. A total of 1959 eligible women were 
randomized in a 2:1 ratio to receive either the dapivirine vaginal ring or placebo vaginal 
ring. This trial was initiated in March 2012 and is expected to complete in 2016/2017.  
 
MTN-020 has been designed to assess the safety and effectiveness of the Dapivirine 
Vaginal Ring-004, inserted once every 4 weeks, in healthy, sexually active, HIV-negative 
women, 18 to 45 years of age, when compared to a placebo vaginal ring. It is conducted 
in Malawi, South Africa, Uganda and Zimbabwe. A total of 2629 women were 


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randomized. Each participant will use the investigational product until 120 events (HIV-1 
seroconversions) are observed in the trial. All participants are anticipated to use the 
investigational product for a minimum of 12 months. The trial was initiated in August 
2012 and clinical conduct completed in June 2015.  
 
 
1.4.3. Adherence to and Acceptability of the Dapivirine Vaginal Ring 
IPM 011 was an open-label, crossover trial conducted in South Africa and Tanzania 
among sexually active women to assess the safety and acceptability of a silicone 
elastomer placebo vaginal ring (containing no active ingredient), intended as a 
microbicide delivery method for the prevention of HIV infection. Participants were 
randomly assigned in a 1:1 ratio to one of two trial groups. Both groups participated in 
two regimens: a placebo vaginal ring regimen and an observational safety regimen (with 
no placebo vaginal ring). Each regimen had 12-week duration. Eighty-two percent (82%) 
of women in this trial reported no ring removals at all for the entire duration of the trial, 
across trial groups and visits, and 99% of participants reported wearing the ring for at 
least 80% of the days they were meant to. Eighteen percent (18%) of women self-
reported at least one ring removal or expulsion during the course of trial participation. 
This proportion increased to 22% when pharmacy records were incorporated. Many of 
the reported expulsions and removals were related to menses, e.g. heavy blood flow or 
concern about the ring becoming dirty or retaining odour, leading to removal. Ninety-five 
percent (95%) of women found the ring to be very comfortable. All questionnaire 
responders were willing to use the vaginal ring if shown to be effective for HIV 
prevention6. 
 
IPM 015 was a Phase I/II randomized, double-blind, placebo-controlled trial conducted at 
10 research centres in Kenya, Malawi, Tanzania and South Africa. The trial was 
performed in 280 HIV-negative, sexually active women, 18 to 40 years of age, to assess 
and compare the safety of 28-day use of Dapivirine Vaginal Ring-004, and a placebo 
vaginal ring, containing no dapivirine. Eligible women were randomly assigned in a 1:1 
ratio to the dapivirine ring or placebo ring,  inserted once every 28 days over a 12-week 
period.  In IPM 015, “perfect adherence” was reported by 92% of the female participants.  
Perfect adherence was defined as never having the ring out for more than an entire day. 
The most frequent activity associated with ring expulsion was urination/defecation and 
the most common reason reported by participants for removing the ring themselves was 
cleaning.  At the end of the trial, 96% of participants reported that the ring was usually 
comfortable to wear, and 97% reported that they would be willing to use it in the future if 
it were proven effective and they thought they were at risk for HIV infection. Just over 
60% of the participants in both arms reported that their male partners did not feel the ring 
at Visit 5 (study week 12). A further 22% reported that their partner felt the ring during 
sex, but that it was not a problem. Only a small number (3%) at Visit 3 (study week 4) 
and (1%) at Visit 5 (study week 12) reported that her male partner felt the ring and it 
might be, or definitely was a problem for her to continue ring use7. 
 
 
1.4.4. Condom Compatibility 
Two clinical condom functionality studies (one with male condoms [IPM 029] and one 
with female condoms [IPM 033]) were conducted with a placebo vaginal ring 
(silicone elastomer ring containing no active ingredient). Results from both studies 
showed that the difference between the total clinical failure rate between condom 
use with the vaginal ring and condom use without the vaginal ring was less than the 


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pre-defined non-inferiority margins (3% for the male condom study and 8% for the 
female condom study). Condom use was safe and well tolerated with vaginal ring 
use.  
 
Studies with dapivirine-containing vaginal gel formulations (0.05%, 2.5 g) were 
conducted on the following types of male and female condoms: 
• 
Non-lubricated latex condoms (male condom) 
• 
Silicone lubricated latex condoms (male and female condoms) 
• 
Aqueous lubricated latex condoms (male condom) 
• 
Polyurethane condoms with silicone lubricant (male and female condoms) 
• 
Nitrile condoms with silicone lubricant (female condom) 
 
All types of condoms met the acceptance criteria established in the protocol for the mean 
values of the treated samples after treatment with dapivirine gels. The results of condom 
compatibility testing indicate that dapivirine-containing vaginal gel formulations (0.05%, 
2.5 g) have no deleterious effects on the integrity of male or female condoms5. 
 
1.5. Rationale for Protocol IPM 032 
The potential of dapivirine as a safe and efficacious microbicide for prevention of sexual 
transmission of HIV has been evaluated in nonclinical studies (virology studies, 
secondary/safety pharmacology, pharmacokinetics, toxicology) using different in vitro, ex 
vivo and in vivo models, as well as Phase I-II clinical trials. Once results from the two 
pivotal Phase III clinical trials demonstrate that the dapivirine vaginal ring is safe and 
efficacious, these results will be communicated to the relevant local and international 
regulatory authorities, IRBs/IECs, community representatives, participants and key 
stakeholders, as appropriate, before activation of IPM 032. 
 
IPM 032, a Phase IIIb follow-on trial to IPM 027, has been designed as an open-label 
clinical trial to collect additional safety data and establish adherence to ring use of the 
Dapivirine (25 mg) Vaginal Ring-004 in healthy, HIV-negative women with monthly (at 
least one to a maximum of three months) followed by 3-monthly research centre follow-
up visits over 12 months. Further, IPM 032 will examine incidence of HIV-1 
seroconversion and monitor HIV-1 resistance in women who acquire HIV-1 infection. 
The assessment of the monthly visits (first one to three months) followed by 3-monthly 
research centre follow-up visits will provide insight into the feasibility of a 3-monthly 
scheduling strategy that would be less costly and time-consuming in a resource-limited 
environment such as sub-Saharan Africa.  
2. Trial Objectives 
2.1. Trial Objectives 
The primary trial objectives are: 
1. 
To assess the safety profile of the 25 mg Dapivirine Vaginal Ring-004, when 
inserted at monthly intervals, in an open-label trial  
2. To assess adherence to the use of the 25 mg Dapivirine Vaginal Ring-004 
inserted at monthly intervals, in an open-label trial  


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The secondary trial objectives are: 
1. To assess the incidence of HIV-1 seroconversion 
2. To assess the frequency of HIV-1 drug resistance in women who acquire HIV-1 
infection 
 
The exploratory trial objectives are: 
1. To assess the feasibility of  3-monthly follow-up visits, as a possible schedule for 
post-licensure vaginal ring clinical follow-up 
2. To explore the correlation between drug concentrations and results from the 
visual inspection of the returned vaginal rings by research staff between the 
monthly and 3-monthly research centre follow-up schedules 
3. To determine the proportion of participants  electing to undergo HIV rapid tests at 
the research centres between scheduled 3-monthly visits 
 
2.2. Trial Endpoints and Assessments 
The primary endpoints are: 
1. Safety  
• 
All Adverse Events (AEs) assessed by the investigator to be related to the 
Dapivirine Vaginal Ring-004 
• 
All Grade 3 and 4 AEs 
• 
All Serious Adverse Events (SAEs) 
 
2. Adherence 
• 
Residual amounts of dapivirine in returned rings; and/or dapivirine 
concentrations in plasma and/or dapivirine concentrations in vaginal fluid  
 
The primary endpoints will be assessed through: 
1. Safety  
• 
All product-related AEs, Grade 3 or 4 AEs, SAEs, physical examination, 
gynaecological 
assessments, 
including 
pelvic/speculum 
examination, 
laboratory tests and other indicated investigations 
2. Adherence 
• 
Determined dapivirine residual amounts in returned used vaginal rings and/or 
• 
Measured concentrations of dapivirine in plasma and/or 
• 
Measured concentrations of dapivirine in vaginal fluids 
 
The secondary endpoints are: 
• 
The HIV-1 seroconversion rate per 100 woman-years of product use at the 
end of the vaginal ring use period 
• 
HIV-1 drug resistance mutations among participants who acquire HIV-1 
infection 


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The secondary endpoints will be assessed through: 
• 
Rapid and specialised laboratory testing according to a pre-specified HIV 
testing algorithm 
• 
Viral genotype resistance testing methods 
 
 
The exploratory endpoints are: 
• 
Feasibility of 3-monthly clinical follow-up schedule 
• 
Dapivirine residual amounts in returned used vaginal rings and/or dapivirine 
concentrations in blood and/or vaginal fluid in correlation with results from the 
visual inspection of the returned used vaginal rings by research staff 
• 
Proportion of participants opting for HIV rapid tests at the research centre 
between scheduled 3-monthly research centre follow-up visits 
 
The exploratory endpoints will be assessed through: 
• 
Participant report of feasibility regarding a 3-monthly clinical follow-up 
schedule (Participant Questionnaire) 
• 
Number of women opting not to receive two additional rings at the 3-monthly 
visits 
• 
Proportion of returned rings (used and unused) during the 3-monthly clinical 
follow-up schedule 
• 
Dapivirine residual amounts in returned used vaginal rings and/or dapivirine 
concentrations in blood and/or vaginal fluid 
• 
Visual inspection of the returned used vaginal rings by research centre staff 
• 
Number of participants undergoing HIV rapid tests at the research centres 
between scheduled 3-monthly research centre follow-up visits 
3. Overall Trial Design 
3.1. Trial Design 
IPM 032 is a Phase IIIb, multi-centre follow-on open-label trial to evaluate the continued 
adherence to and safety of the Dapivirine Vaginal Ring-004, inserted at monthly intervals 
in healthy, HIV-negative women who have participated in the IPM 027 Phase III 
Dapivirine Vaginal Ring-004 trial. All women who have participated in IPM 027 and are 
HIV-negative at screening for IPM 032 will be eligible. An estimate of approximately 
1400 participants will be enrolled.  All participants will receive the dapivirine vaginal ring 
containing 25 mg dapivirine (Ring-004) at enrolment and will attend a research centre 
follow-up visit one month after enrolment.  Following this visit, at investigator’s discretion, 
a participant can continue on a 3-monthly visit schedule.   Monthly visits may however be 
extended up to the first three months of participation. Once the 3-monthly trial visit 
schedule commences, three rings will be dispensed.  One ring will be self-inserted at the 
research centre and two additional rings will be dispensed for the participant to take 
home, or dispensing will take place as arranged with the participant.  
 


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3.2. Trial Duration 
Each participant will engage in the screening process for up to 45 days prior to 
enrolment and will use the Dapivirine Vaginal Ring-004 for a period of up to 12 months. 
IPM will have the option to extend this trial period. Accrual will take place over 
approximately 6 months and those participants who are enrolled more than 6 months 
after the onset of the study site’s accrual period may have a shortened follow-up period. 
 
Each participant will have an exit visit 1-2 months after ring discontinuation, to assess 
safety and identify HIV seroconversions after product discontinuation.   
 
3.3. Trial Population 
Approximately 1400 HIV-negative women who have participated in the IPM 027 Phase 
III Dapivirine Vaginal Ring-004 trial, who understand the trial, and can provide informed 
consent are expected to enrol in this open-label trial.   
 
3.3.1. Inclusion Criteria 
Women must meet all the following criteria to be eligible to enrol in the trial: 
 
1. Previously enrolled in the IPM 027 trial 
2. Available for all visits and consent to follow all procedures scheduled for the trial 
3. Using an effective method of contraception at the Enrolment Visit, and intending 
to use an effective contraceptive method for the duration of trial participation, 
unless post-menopausal with no history of menses for one year prior to screening   
4. HIV-negative as determined by the HIV algorithm applied at Screening/Pre-
Enrolment 
5. Willing to refrain from participation in another research trial using drugs, vaccines, 
medical devices and microbicides for the duration of the IPM 032 trial 
6. Willing to provide adequate locator information for trial retention purposes and be 
reachable per local standard procedures (e.g., by home visit or telephone; or via 
family or close neighbour contacts); confidentiality to be maintained 
 
3.3.2. Exclusion Criteria 
Women who meet any of the following criteria are NOT eligible to enrol in the trial: 
 
1. Investigational product use permanently discontinued in response to an AE 
(where the AE was considered related to investigational product) or safety-related 
concern while taking part in the IPM 027 trial  
2. Participant self-report of taking post-exposure prophylaxis (PEP) within ≤ 2 
months at Screening Visit 
Note: Participants may be enrolled after completing the PEP regimen and a 
negative HIV test was documented at least 2 months prior to screening for IPM 
032 
3. Currently pregnant, intends to become pregnant or currently breast-feeding 
4. Known drug abuse or alcohol dependence in the 12 months prior to screening 


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5. Participated in another research trial (other than IPM 027) using drugs, medical 
devices, microbicides or oral pre-exposure prophylaxis agents within 30 days prior 
to screening 
6. Any new illness or condition(s), chronic condition(s) or abnormal laboratory 
finding(s) that, in the opinion of the investigator, might put the participant at risk, or 
interfere with the trial objectives or the participant’s adherence to trial 
requirements 
4. Trial Visits and Procedures 
4.1. Screening Visit  
NOTE: For potential participants who do not meet the eligibility criteria, screening 
procedures will be discontinued once ineligibility has been determined. Women who fail 
screening may be re-screened once and may be enrolled if they are found to meet ALL 
inclusion and NO exclusion criteria at the second screening visit.  
 
In the event that the IPM 027 trial is stopped prematurely and IPM 032 is activated at the 
research centre, the IPM 027 LPUV and the IPM 032 Screening and Enrolment Visits 
may be combined for participants who are eligible to enrol in the IPM 032. In these 
situations, a separate Screening visit will not be required, and only the procedures 
indicated in italics are required. 
 
a. Explain the screening, enrolment and trial procedures to the potential participant.  
b. If the potential participant agrees, obtain written informed consent. Illiterate 
participants may provide a thumbprint or mark witnessed and signed by a person 
independent from trial staff (refer to Section 5.1). A comprehension assessment 
checklist will be used to support the consent process (refer to Section 5.2).  
c. Assign a unique SCR-ID number to the potential participant.  
d. Conduct a review of inclusion/exclusion criteria with the potential participant.  
e. Collect demographic information from the potential participant.  
f. Obtain and record locator information.  
g. Record basic menses information, relevant medical history, and concomitant 
medication taken within the last 30 days (refer to Section 5.7 for more details 
about relevant medical history).  
h. Perform urine pregnancy testing. Refer pregnant women to local prenatal clinic 
for support services (refer to Section 5.6).  
i. 
Provide HIV/STI risk-reduction counselling (including provision of male condoms, 
should participants wish to receive them), contraceptive counselling and the 
provision of contraceptives, if necessary (refer to Sections 5.3.2 and 5.5).  
j. 
Provide HIV pre- and post-test counselling (refer to Section 5.3.1).  
k. Perform HIV rapid testing as detailed in Section 5.4.1.  
l. 
Collect a blood specimen by venepuncture for storage for possible HIV viral 
genotype resistance and HIV-RNA PCR testing (Blood volume specified in 
Appendix C). 
m. Perform general physical examination (refer to Section 5.8 for a description of the 
elements required in the general physical examination).  


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n. Perform a pelvic examination (refer to Section 5.9). If the pelvic examination 
indicates abnormal findings, e.g., any symptoms or evidence of genital infections, 
abrasions, ulcerations, etc., provide or refer for appropriate treatment.  
NOTE: If the participant is menstruating at this visit, the pelvic examination may 
be conducted as per investigator and participant discretion. If this is not possible, 
the participant will be asked to return 2 days after completion of menstruation.  
o. Collect cervicovaginal swabs for STI testing and a specimen for cervical cytology, 
if no result is evident within the previous year, or abnormal at last cervical 
cytology (refer to Sections 5.11.1 and 5.12).  
p. Provide treatment and/or referral for STIs and other findings, as necessary (refer 
to Section 5.11.2). 
q. Perform a urine dipstick analysis (microscopy only if clinically indicated). Collect 
blood samples by venepuncture for syphilis testing (RPR) and confirmatory test 
(if required), and the following safety laboratory tests (Blood volumes specified in 
Appendix C): haematology (FBC with differential and platelet count), and 
chemistry (creatinine, ALT, AST) (refer to Section 5.10).  
r. Other procedures, as clinically indicated and with prior approval from IPM. 
s. Schedule the Enrolment Visit within 45 days 
  
4.2. Enrolment Visit 
Note: The Enrolment Visit will occur within 45 days after the Screening Visit.  
 
In the event that the IPM 027 trial is stopped prematurely and the IPM 032 is activated at 
the research centre, the IPM 027 LPUV and the IPM 032 Screening and Enrolment Visits 
may be combined for participants who are eligible to enrol in IPM 032. Trial procedures 
conducted as part of the IPM 027 LPUV will not be repeated for the IPM 032 trial. Only 
the procedures indicated in italics are required. 
 
Pre-enrolment: 
a. Update locator, menses and pre-enrolment medical history information as 
necessary (refer to Section 5.7).  
b. Provide contraceptive counselling and contraceptives, if necessary (refer to 
Section 5.5).  
c. Provide HIV/STI risk reduction counselling, including provision of male condoms 
if the participant wishes to receive them (refer to Section 5.3.2).  
d. Record possible social harms (refer to Section 10.2)  
e. Obtain and record any concomitant medication information since the last visit.  
f. Perform urine pregnancy testing. Refer pregnant women to local prenatal clinic 
for support services (refer to Section 5.6).  
g. Provide HIV pre- and post-test counselling (refer to Section 5.3.1).  
h. Perform HIV rapid testing as detailed in Section 5.4.2.  
NOTE: Additional procedures for participants who test HIV-positive are also 
described in Section 5.4.2 of the protocol.  
i. 
Reassess and confirm eligibility. 


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Post-enrolment: 
j. 
Assign a unique PID number to the participant.   
k. Collect a blood specimen by venepuncture for storage for possible HIV viral 
genotype resistance and HIV-RNA PCR testing (Blood volume specified in 
Appendix C). 
l. 
Obtain and record any AE information.  
m. Provide adherence counselling, including adherence to trial visit schedule and 
requirements and vaginal ring adherence (refer to Section 5.15). At the 
Enrolment Visit, participants will be provided with feedback on the IPM 027 and 
MTN-020 trial results during the vaginal ring adherence counselling. Participants 
will be instructed to keep the ring inserted for a period of one month. Adherence 
counselling will include information on actions that should be taken in the event of 
expulsion or removal of the ring. If the ring comes out or is removed during this 
period, the participant should wash her hands, rinse the ring thoroughly in clean 
water and re-insert it.  
n. Provide and explain the use of the diary card to the participant (refer to Section 
5.19). 
o. Dispense one vaginal ring to each participant and provide vaginal ring use and 
storage instructions (refer to Sections 5.13 and 6.4). 
p. Instruct the participant to insert the vaginal ring (refer to Section 5.14). 
q. The following procedures are not required, but may be conducted if clinically 
indicated: physical and pelvic examination, cervicovaginal sample collection for 
STI testing, provision of treatment and/or referral for STIs and other findings, 
laboratory testing for safety assessments, urine dipstick analysis (microscopy 
only if clinically indicated) and cervical sample collection for cytology (if no result 
is evident within the previous year, or abnormal at last cervical cytology). 
r. Schedule the next visit. 
 
4.3. Trial Visits (Monthly research centre visits for the first one to three 
months, and 3-monthly research centre visits thereafter) 
Note: All visit dates will be calculated from the enrolment visit as baseline date. Each 
scheduled visit while the participant is on the IP has a window period of ± 7 days. 
 
a. Update locator and menses information as necessary.  
b. Obtain and record any AE and concomitant medication information since the last 
visit.  
c. Record possible social harms (refer to Section 10.2). 
d. Perform urine pregnancy test. Refer pregnant women to local prenatal clinic for 
support services (refer to Section 5.6).  
e. Provide HIV pre- and post-test counselling (refer to Section 5.3.1).  
f. Perform HIV rapid testing as detailed in Section 5.4.3.  
NOTE: Additional procedures for participants who test HIV-positive are also 
described in Section 5.4.3 of the protocol. 


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g. Collect a blood specimen by venepuncture for storage for possible HIV viral 
genotype resistance and HIV-RNA PCR testing (Blood volume specified in 
Appendix C). 
h. Collect blood (Blood volume specified in Appendix C) and vaginal fluid samples 
(refer to Section 5.17) for possible measurement of dapivirine concentrations. 
NOTE: For dapivirine concentration measurements, blood and vaginal fluid 
samples should preferably be collected prior to removal of the vaginal ring.   
i. 
Instruct the participant to remove the vaginal ring. Perform IP accountability and 
visual inspection of the returned ring(s). Returned rings may be analysed for 
residual amounts of dapivirine and will be stored until shipment to the analytical 
laboratory. 
Dispense one vaginal ring to participants during monthly visits and three vaginal 
rings during 3-monthly visits (or dispense as arranged with the participant) and 
provide vaginal ring use and storage instructions (refer to Sections 5.13 and 6.4).  
j. 
Instruct the participant to insert the vaginal ring during monthly visits.   Once the 
3-monthly trial visit schedule commences, one ring will be inserted at the 
research centre and two additional rings will be dispensed for the participant to 
take home (or dispense as arranged with the participant (refer to Section 5.14).  
k. Collect and review the diary card(s) and provide a new diary card(s) if applicable 
(refer to Section 5.19).  
l. 
Administer the Participant Questionnaire at every trial visit (refer to Section 5.16). 
m. Provide adherence counselling, including adherence to trial visit schedule and 
requirements, and vaginal ring adherence (refer to Section 5.15). Participants will 
be instructed to keep the ring inserted for a period of one month. Adherence 
counselling will include information on actions that should be taken in the event of 
expulsion or removal. If the ring comes out or is removed during this period, the 
participant should wash her hands, rinse the ring thoroughly in clean water and 
re-insert it.  
n. Provide contraceptive counselling and contraceptives, if necessary (refer to 
Section 5.5).  
o. Provide HIV/STI risk reduction counselling; including provision of male condoms 
if the participant wishes to receive them (refer to Section 5.3.2).  
p. The following procedures are not required, but may be conducted if clinically 
indicated: physical and pelvic examination, cervicovaginal sample collection for 
STI testing, provision of treatment and/or referral for STIs and other findings, 
laboratory testing for safety assessments, urine dipstick analysis (microscopy 
only if clinically indicated) and cervical sample collection for cytology (if no result 
is evident within the previous year, or abnormal at last cervical cytology). 
q. Schedule the next visit.  
 
4.4. Last Product Use Visit (LPUV) or Early Discontinuation Visit  
Note: LPUVs will be calculated from the enrolment visit as baseline date. This scheduled 
visit has a window period of ± 7 days. 
 
a. Update locator and menses information as necessary.  


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b. Obtain and record any AE and concomitant medication information since the last 
visit.  
c. Perform a pelvic examination (refer to Section 5.9). If the pelvic examination 
indicates abnormal findings, e.g., any symptoms or evidence of genital infections, 
abrasions, ulcerations, etc., provide the participant with or refer the participant for 
appropriate treatment.  
NOTE: If the participant is menstruating at this visit, the pelvic examination may 
be conducted as per investigator and participant discretion. If this is not possible, 
the participant will be asked to return 2 days after completion of menstruation.  
d. Record possible social harms (refer to Section 10.2)  
e. Perform a general physical examination (refer to Section 5.8 for a description of 
the elements required in the general physical examination).  
f. Instruct the participant to remove the vaginal ring. Perform IP accountability and 
visual inspection of the returned ring(s). Returned rings may be analysed for 
residual amounts of dapivirine and will be stored until shipment to the analytical 
laboratory. 
g. Collect and review the diary card(s).  
h. Administer the Participant Questionnaire (refer to Section 5.16). 
i. 
Provide HIV/STI risk reduction counselling; including provision of male condoms 
if the participant wishes to receive them (refer to Section 5.3.2).  
j. 
Perform contraceptive counselling and provide contraceptives, if necessary (refer 
to Section 5.5).  
k. Perform urine pregnancy test. Refer pregnant women to local prenatal clinic for 
support services (refer to Section 5.6).  
l. 
Collect cervicovaginal swabs for STI testing (refer to Sections 5.11.1).  
m. Provide STI treatment if needed (refer to Section 5.11.2). 
n. Provide HIV pre- and post-test counselling (refer to Section 5.3.1).  
o. Perform HIV rapid testing as detailed in Section 5.4.3.  
p. Collect a blood specimen by venepuncture for storage for possible HIV viral 
genotype resistance and HIV-RNA PCR testing (Blood volume specified in 
Appendix C). 
q. Collect blood (Blood volume specified in Appendix C) and vaginal fluid samples 
(refer to Section 5.17) for possible measurement of dapivirine concentrations. 
NOTE: For dapivirine concentration measurements, blood and vaginal fluid 
samples should preferably be collected prior to removal of the vaginal ring.   
r. The following procedures are not required, but may be conducted if clinically 
indicated: laboratory testing for safety assessments, urine dipstick analysis 
(microscopy only if clinically indicated) and cervical sample collection for cytology 
(if no result is evident within the previous year, or abnormal at last cervical 
cytology).  
s. Schedule the exit visit. 
 
 


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4.5. Exit Visit 
Note: Exit Visits will occur 1-2 months after ring discontinuation. If the outcome of 
confirmatory tests is pending, the exit visit may be conducted more than 2 months after 
the last product use visit, but should be performed as soon as possible after the results 
are available. Participants will be notified of any abnormal laboratory findings, and return 
to the research centre prior to the exit visit as needed for treatment and/or referral. 
Additional trial procedures for exit visits scheduled following HIV seroconversion are 
described in Section 5.4.4. 
 
a. Obtain and record any AE and concomitant medication information since the last 
visit.  
b. Record possible social harms (refer to Section 10.2). 
c. Perform contraceptive counselling and provide contraceptives, if necessary (refer 
to Section 5.5).  
d. Provide HIV/STI risk reduction counselling; including provision of male condoms 
if the participant wishes to receive them (refer to Section 5.3.2).  
e. Provide HIV pre- and post-test counselling (refer to Section 5.3.1).  
f. Perform HIV rapid testing as detailed in Section 5.4.4 (additional procedures for 
participants who test HIV-positive are also described in Section 5.4.4 of the 
protocol).  
g. Collect a blood specimen by venepuncture for storage for possible HIV viral 
genotype resistance and HIV-RNA PCR testing (Blood volume specified in 
Appendix C). 
h. Provide final safety and STI laboratory test results to participant.  
i. 
The following procedures are not required, but may be conducted if clinically 
indicated: physical and pelvic examination, cervicovaginal sample collection for 
STI testing, provision of treatment and/or referral for STIs and other findings, 
laboratory testing for safety assessments, urine dipstick analysis (microscopy 
only if clinically indicated) and cervical sample collection for cytology (if no result 
is evident within the previous year, or abnormal at last cervical cytology). 
j. 
Exit the participant from the trial.  
 
4.6. Unscheduled Visits 
Unscheduled visits may be performed at any time during the trial for HIV, STI or 
pregnancy testing, collection of an additional ring , or if the participant is experiencing 
any problems, e.g., vaginal complaints, difficulties with re-inserting the ring in cases of 
accidental expulsion or ring removal, or accidental loss of the ring. Participants will also 
be notified of any abnormal laboratory findings, and return to the research centre prior to 
the next scheduled visit as needed for treatment and/or referral to an outside medical 
facility. Additional laboratory testing to evaluate AEs that are suspected to be associated 
with use of the IP may be performed where indicated, in consultation with the IPM 
Clinical Physician. 
 
All unscheduled visits will be documented in the source documents and applicable case 
report forms (CRFs). 
 


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4.7. Missed and Late Visits 
Trial staff will make every effort to contact participants to return to the research centre for 
scheduled visits. If a participant does not return to the research centre for a scheduled 
visit during the trial window, e.g., within ± 7 days of a scheduled visit, continued attempts 
to contact the participant will be made as per local standard operating procedure (SOP) 
and documented in the source documents. 
 
If the participant does not return to the research centre for a scheduled visit prior to the 
start of the trial window of the next visit, the visit will be considered missed. For example, 
if a participant does not return for Visit 2 by the time the trial window has begun for Visit 
3, i.e., within 7 days from Visit 3, Visit 2 will be considered missed. Trial procedures will 
be performed as scheduled for the current visit (e.g. Visit 3 in this instance) or as 
deemed necessary by the investigator or IPM Clinical Physician (or designee). Missed 
visits will be documented as protocol deviations. Trial staff should ensure that all used or 
unused vaginal rings that were to be returned at the missed visit are retrieved as soon as 
possible. 
 
In the event that a participant will be away and unable to attend one of the Trial Visits 
where new vaginal rings would be dispensed, the investigator or designee could 
dispense additional ring(s) on a case-by-case basis. Research centre staff will enquire 
about adverse events and concomitant medication over the telephone; and other 
information will be collected as applicable.  
 
If a participant presents for a visit outside the window for a scheduled trial visit but prior 
to the start of the window for the next visit, it will be treated as a late visit and 
documented as a protocol deviation. All trial procedures scheduled for the late 
scheduled visit will still be performed. The participant will then resume her original visit 
schedule. 
 
If a LPUV is missed, STI testing should be performed at the Exit Visit. 
 
4.8. Protocol Deviations 
A protocol deviation is defined as any change, non-compliance or divergence from the 
approved protocol. The non-compliance may be either on the part of the participant, the 
investigator, the research centre staff or laboratory staff. It is the responsibility of the 
research centre to identify and report protocol deviations according to the guidelines of 
the sponsor and the local IRB/IEC. The research centre must report protocol deviations 
to IPM using designated forms. The principal investigator and research centre staff are 
responsible for being familiar with and adhering to their IRB/IEC requirements. In 
response to noted protocol deviations, research centre personnel are to promptly 
implement corrective actions. 
 
4.9. Early Discontinuation Visits 
Participants may be discontinued early from the trial prior to completion of the last trial 
visit for any of the following reasons: 
• 
Participant withdraws her consent. 
• 
Participant fails to follow protocol requirements which are deemed to be 
serious enough by the investigator to warrant a discontinuation, e.g., in the 


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absence of an AE or discomfort, participant refuses to keep vaginal ring 
inserted for duration of the trial. 
• 
Participant is lost to follow-up, i.e., research centre is unsuccessful (following 
reasonable attempts as defined in the research centre SOP) in contacting 
participant or bringing the participant back to the research centre. 
• 
Participant tests HIV-positive according to the HIV-testing algorithm in 
Appendix B.  
• 
If, for safety reasons, the investigator considers it in the best interest of the 
participant to discontinue her from the trial.  
• 
At the discretion of the investigator, Sponsor, IRB/IEC or the government 
health authority. 
The date and reason for permanent trial discontinuation will be noted in the source 
documents and applicable CRFs. All participants who are prematurely discontinued from 
the trial will be encouraged to return to the research centre for a final evaluation, at 
which time all trial procedures scheduled for the last product use visit will be performed. 
An optional exit visit 1-2 months after product discontinuation can be completed. 
 
Participants who are considered lost to follow-up will be temporarily discontinued from 
the trial. Reasonable contact attempts will be made according to the locator information 
provided by the participant and local SOPs, and temporarily early trial termination will be 
documented in the source documents and applicable CRFs. If a participant already 
considered lost to follow-up returns to the research centre prior to the centre’s trial 
completion, the participant’s file (including CRFs) may be re-opened to perform trial 
discontinuation procedures. The participant may be considered for continuation on the 
trial at the discretion of the principal investigator in consultation with the IPM Clinical 
Project Manager, depending on the reason for the missed visits. A final trial termination 
will be documented in the source documents and applicable CRFs during the trial 
closure for all temporarily early trial terminations. 
 
4.10. Premature Discontinuation of the Trial 
IPM has the right to terminate this trial at any time for any reason. If the trial is 
prematurely terminated, the investigator must promptly inform the participants and the 
IRBs/IECs, and ensure proper medical follow-up of participants in consultation with IPM. 
If the trial is prematurely terminated, all procedures and requirements pertaining to the 
archiving of the trial documents will be observed. IPM will provide the research centres 
with instructions on the proper disposition of any clinical supplies at the centre.  
5. Trial Procedure Details  
5.1. Informed Consent 
The informed consent documents will include all the information about the trial required 
by GCP and will make provision for the dated signatures of the participant, the principal 
investigator or designated trial staff conducting the informed consent process, and when 
required, also for a dated signature by an impartial witness. The informed consent 
process will be administered at the Screening Visit. 
 
The informed consent process will include adequate time for each potential participant to 


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have any trial related questions answered by appropriately qualified and trained trial staff 
as designated by the investigator, and the entire process will be documented in the 
source documents. 
 
At screening, potential participants who agree to participate in the trial will sign and date 
the ICF. The ICF will also be signed and dated by the trial staff administering the consent 
process as delegated by the principal investigator according to the research centre SOP. 
If a potential participant is functionally illiterate, the informed consent document(s) and 
any written study-related materials must be read to her in the language best understood 
by the potential participant in the presence of an impartial literate witness. After the 
illiterate participant has orally consented to participate in the trial, and, if capable of 
doing so, has signed the ICF or provided a thumbprint or mark that was witnessed by the 
impartial witness, this impartial witness must sign and personally date the ICF. By 
signing the ICF the impartial witness attests that the information in the participant 
information sheet and any other written information was explained to, and apparently 
understood by, the participant or the participant’s legally acceptable representative and 
that informed consent was freely given by the participant or the participant’s legally 
acceptable representative. 
 
The signed and dated ICFs will be retained at the research centre. A copy of the signed 
and dated ICFs will be offered to the participant. If the participant is not willing to receive 
the documents, the second copy will be retained at the research centre. Likewise, during 
the trial, signed and dated ICF updates and any amendments to written trial-related 
materials to be given to participants will be offered to the participant but retained at the 
research centre if the participant is unwilling to receive the documents. Documentation of 
the participant’s refusal to accept a copy of the ICF(s) or other trial-related materials will 
be noted in the source documents.  
 
The consent documents and any trial-related materials given to the participant will be 
translated and back-translated in the local languages according to local IRB/IEC 
requirements and regulatory authority guidelines. Information in the informed consent 
documents and trial-related material will be verbally communicated by trial staff, in the 
language preferred by the participant, and copies of the documents and trial-related 
materials will be offered to her in her preferred language. Documentation will be required 
to verify who performed translation/back-translation of the materials as well as a written 
statement by the translator indicating that the consent form(s) is an accurate translation 
of the accompanying English version. This is the principal investigator’s responsibility. 
 
All research centre-specific informed consent documents will first be reviewed and 
approved by IPM and then approved by the responsible IRB and/or local IEC prior to 
administration to the participants. 
 
If new information becomes available which may be relevant to the participant’s 
willingness to continue trial participation, the information will be provided via IRB and/or 
IEC-approved revised informed consent documents or addenda to the original informed 
consent documents in a timely manner and will be signed and dated by the participant in 
the same manner described above. 
 
 


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5.2. Comprehension Assessment Checklist  
Trial staff will assess the potential participant’s understanding of informed consent 
information prior to obtaining a signature on the ICF at the Screening Visit. This 
assessment will be done using a standardised comprehension assessment checklist. All 
comprehension problems that are discovered during the assessment will be discussed 
until staff member(s) are satisfied that the participant can verbalise her understanding of 
the issue. This process will be documented on the comprehension assessment checklist. 
This checklist will be recorded in source documentation at the research centre. A 
participant who cannot demonstrate comprehension of the informed consent information 
will not be enrolled in the trial. 
 
5.3. HIV Counselling 
5.3.1. HIV Pre-and post-Test Counselling 
At all visits where HIV testing is performed, pre- and post-test counselling will be 
provided according to the National Guidelines for HIV Counselling and Testing. 
Adaptations of these guidelines in accordance with locally accepted standards of 
practice are allowed. Each research centre will document the counselling policies and 
procedures prior to trial implementation for purposes of staff training, quality assurance, 
and trial monitoring. 
 
A comprehensive package of post-test counselling and psychosocial support will be 
provided to women who test HIV reactive at any point during trial participation. Initial 
counselling services will be provided at the research centre and women will be referred 
for additional counselling, support services and treatment. These services will be 
identified by the research centres prior to trial initiation and referral procedures will be 
documented in writing by the centre. 
 
5.3.2. HIV/STI Risk Reduction Counselling 
HIV/STI risk reduction counselling will be in accordance with local guidelines. 
Counselling will be provided at all research centre visits. Efforts will be made to ensure 
standardisation of risk reduction counselling at the trial research centres. 
 
NOTE: Risk reduction counselling will include recommendation of male condom use. 
Participants will be provided with a supply of male non-spermicidal condoms during each 
trial visit, if they are willing to accept them. The use of female condoms is permitted in 
this trial. 
 
5.4. HIV Testing and Management 
The research centres will inform IPM Medical Safety of any new HIV seroconversions 
within 48 hours of diagnosis. The applicable regulatory authorities and independent 
ethics committees who require expedited notification of HIV seroconversion will be 
notified by either IPM or the research centre in accordance with standard operating 
procedures and policies of the regulatory authorities or independent ethics committees. 
The details of the HIV rapid test kits will be specified in the Laboratory Manual, as part of 
the SOM. Participants will be tested for HIV using two highly sensitive antibody rapid 
tests (Test 1 and Test 2). 
 


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5.4.1. Screening Visit 
If both test results are non-reactive, the participant could potentially be enrolled in the 
trial if she is otherwise eligible.  
 
If both Test 1 and Test 2 are reactive at screening, the potential participant is considered 
to be HIV seropositive and not eligible for enrolment. Initial counselling services will be 
provided at the research centre and the participant will be referred for additional 
counselling, support services and treatment. These referral systems will be implemented 
by research centres prior to trial start. It is the participant’s responsibility to follow up with 
relevant medical services once referral has been initiated by the research centre. 
 
If Test 1 and Test 2 yield discordant results, a highly specific HIV antibody Test 3 will be 
performed. If Test 3 is reactive then the potential participant is considered to be HIV-
seropositive and is not eligible for enrolment. If Test 3 is non-reactive, the person is 
considered to be potentially HIV-seronegative and can be given a date for enrolment into 
the trial. Refer to Appendix B: HIV Testing Algorithms. 
 
A blood sample will be obtained by venepuncture to be sent for sample storage locally or 
at a central laboratory, for potential HIV-1 RNA PCR and viral genotype resistance 
testing if the participant seroconverts (blood volume specified in Appendix C). Storage 
samples for participants who do not enrol will be destroyed according to research centre 
SOPs. 
 
NOTE: For the purposes of HIV rapid testing at screening, blood may be obtained by 
finger prick or venous sampling. If the national regulatory authority of the country in 
which the research centre is situated requires that a national testing algorithm be used 
during the screening process, this will be performed, in addition to the IPM 032 HIV 
testing algorithm, as part of the screening process and documented as such. 
 
5.4.2. Enrolment Visit 
On the scheduled day of possible enrolment, the participant will be tested for HIV and 
will only be enrolled if the results are considered to be HIV-seronegative and the 
participant is otherwise eligible.  
 
Test 1 and Test 2 will be performed. If both test results are non-reactive and there is no 
history to suggest recent exposure that could be masked during the window period, the 
potential participant will be considered HIV-seronegative and eligible for enrolment. A 
blood sample will be obtained by venepuncture to be sent for sample storage locally or 
at a central laboratory, for potential HIV-1 RNA PCR and viral genotype resistance 
testing if the participant seroconverts (blood volume specified in Appendix C). Storage 
samples for participants who do not enrol will be destroyed according to local SOPs. 
 
If both Test 1 and Test 2 are reactive, the participant is considered to be HIV 
seropositive and not eligible for enrolment. Initial counselling services will be provided at 
the research centre and the woman will be referred for additional counselling, support 
services and treatment. 
 
A rapid Test 3 will be performed for all discordant rapid test results. If Test 3 is reactive 
then the potential participant is considered to be HIV-seropositive and not eligible for 


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enrolment. If Test 3 is non-reactive, the participant is considered to most likely be HIV-
seronegative, and a sample will be collected for HIV-1 RNA PCR testing and the 
Enrolment Visit should be re-scheduled within the screening window period (split visit). If 
the HIV-1 RNA PCR does not detect HIV RNA copies, the participant can be enrolled. 
Storage samples should be collected on the second day of the split visit. If the HIV-1 
RNA PCR does detect HIV RNA copies then she is not eligible for enrolment. She will be 
counselled and referred to the local health facilities for appropriate follow-up. Refer to 
Appendix B: HIV Testing Algorithms. 
 
5.4.3. Trial Visits and LPUV 
The rapid and confirmatory laboratory tests used in the HIV-testing algorithm will detect 
both subtypes, HIV-1 and HIV-2. The testing algorithm (refer to Appendix B) will be 
applied for all Trial Visits and LPUV. HIV testing while the participant is enrolled in the 
trial will be performed on blood samples obtained by venepuncture (blood volumes 
specified in Appendix C). 
 
If both the HIV rapid tests (Test 1 and Test 2) are non-reactive, the participant will be 
considered HIV-seronegative and continue using the IP. If both HIV rapid tests are 
reactive, IP will be withheld until HIV infection has been confirmed. Trial procedures 
relevant to the LPUV will be performed. Additional confirmatory testing will be performed 
by Western Blot and other confirmatory tests, where appropriate. IP may be re-
introduced after consultation with IPM, if confirmatory test(s) indicate(s) that the 
participant is not HIV infected. The participant must have a negative pregnancy test prior 
to re-introduction of IP. A pelvic examination should be performed according 
investigator’s discretion prior to re-introduction of IP if clinical indicated. If confirmatory 
test(s) indicate(s) that the participant is HIV infected, the participant will be permanently 
discontinued from IP and the trial. 
 
If the Test 1 and Test 2 results are discordant, a HIV rapid Test 3 will be performed on 
the same blood sample as used for Test 1 and Test 2. If Test 3 is reactive, IP will be 
withheld until HIV infection has been confirmed. Trial procedures relevant to the LPUV 
will be performed. Additional confirmatory testing will be performed by Western Blot and 
other confirmatory tests, where appropriate. IP may be re-introduced after consultation 
with IPM, if confirmatory test(s) indicate(s) that the participant is not HIV infected. The 
participant must have a negative pregnancy test result prior to re-introduction of IP. A 
pelvic examination should be performed according investigator’s discretion prior to re-
introduction of IP, if clinical indicated.  Nucleic acid-amplification testing (NAAT) by a 
HIV-1 RNA PCR test will be performed on stored samples in reverse sequential order to 
estimate the time point of HIV infection. The participant will be counselled and referred 
for appropriate counselling and care. 
 
If Test 3 is non-reactive, the participant is considered to be HIV-seronegative. The 
participants who have discordant HIV test results at Trial Visits will continue on IP and be 
requested to return for repeat HIV rapid testing after two weeks. In such cases the 
research centre will notify the IPM Clinical Project Manager or designee. Additional 
confirmatory tests may be indicated at any stage in consultation with the IPM Clinical 
Project Manager or designee. If a similar result is obtained on testing after two weeks, a 
sample should be collected for a quantitative HIV-1 PCR test and the research centre 
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If the HIV-1 RNA PCR result is undetectable: 
• 
The participant is considered to not be HIV-infected. 
• 
The participant should continue in the trial with HIV rapid testing only 
performed at scheduled visits, even if the same pattern of discordant results 
continues. It will not be necessary to recall the participant for 2-weekly 
testing. 
• 
The research centre will notify the IPM Clinical Project Manager or designee 
of the outcome. 
 
If the HIV-1 RNA PCR result is detectable: 
• 
The participant should be considered HIV-infected and IP should be 
discontinued immediately. The research centre will notify the IPM Clinical 
Project Manager or designee immediately. 
 
All enrolled participants will in addition, have blood samples collected at each trial visit to 
be stored locally or at a central laboratory, for possible viral genotype resistance testing 
and HIV-1 RNA PCR testing. If a participant subsequently seroconverts (i.e. is confirmed 
HIV-positive) while on the IP, the stored samples will be tested in reverse sequential 
order until an undetectable PCR test result is obtained. This will be conducted to 
approximate the period of HIV infection. If the enrolment HIV-1 RNA PCR test result is 
positive, the participant is not considered to have been infected while using the IP. 
Blood (blood volume as specified in Appendix C) and vaginal fluid samples will also be 
obtained for dapivirine measurement at the point of HIV seroconversion according to the 
HIV testing algorithm described above. Stored samples (blood and vaginal fluids) will be 
analysed retrospectively as described in Section 5.17. 
 
Any participant who is confirmed HIV-infected while on the trial will be permanently 
discontinued from IP and the trial. An exit visit will be scheduled approximately 1-2 
months following IP discontinuation. Initial counselling services will be provided at the 
research centre and women will be referred for additional counselling, support services 
and treatment. In addition, these women will be offered the option of enrolling for IPM’s 
seroconverter protocol. 
 
In an instance where a participant is determined to be HIV-seropositive (as determined 
by HIV rapid tests, Western Blot; and any other confirmatory tests, if applicable), but 
cannot be confirmed as HIV-infected (HIV RNA PCR) the participant will be discontinued 
from IP and the protocol-required procedures as per original  trial visit schedule will be 
conducted at the investigator’s discretion. Samples for measurement of dapivirine levels 
will no longer be collected. Additional testing to demonstrate HIV infection may be 
performed. Participants will be followed up until the exit visit according to the original 
enrolment date. 
 
5.4.4. Exit Visit  
For participants confirmed as HIV-negative prior to the exit visit 
If both HIV rapid tests (Test 1 and Test 2) are non-reactive, the participant will be 
considered HIV-seronegative. If both Test 1 and Test 2 are reactive, additional 
confirmatory testing will be performed by Western Blot and other confirmatory tests, 
where appropriate. Samples for possible viral genotype resistance testing and HIV-1 


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RNA PCR testing will be collected. Once HIV infection has been confirmed, this will be 
considered an HIV seroconversion after product discontinuation and may be a 
combination of both women infected during IP use who seroconverted after IP 
discontinuation, as well as women infected after IP use. Nucleic acid-amplification 
testing (NAAT) by a HIV-1 RNA PCR test will be performed on stored samples in reverse 
sequential order to estimate the time point of HIV infection. 
 
Initial counselling services will be provided at the research centre and women will be 
referred for additional counselling, support services and treatment. 
 
A HIV rapid Test 3 will be performed for discordant rapid Test 1 and Test 2 results. If 
Test 3 is reactive then the participant will be considered to be HIV-seropositive. 
Additional confirmatory testing will be performed by Western Blot and other confirmatory 
tests, where appropriate. Samples for possible viral genotype resistance testing and 
HIV-1 RNA PCR testing will be collected. The participant will be counselled and referred 
to local health facilities for social support or other medical services as clinically indicated. 
If Test 3 is non-reactive, the participant is considered to be HIV-seronegative and will be 
counselled appropriately. Refer to Appendix B: HIV Testing Algorithms, and Appendix C: 
Visit Schedule and Blood Volumes. 
 
For participants confirmed as HIV-infected prior to the exit visit 
As stated in Section 5.4.3 above, an exit visit will be scheduled approximately 1-2 
months following confirmed HIV-seroconversion and IP discontinuation. Blood samples 
for viral genotype resistance testing and HIV-1 RNA PCR will be collected from these 
participants, but no further HIV counselling and testing will be done unless indicated for 
additional confirmatory testing. 
 
Participants who become infected with HIV during the course of an IPM trial will be 
referred for appropriate HIV-related care and ARV therapy as above. The threshold for 
initiation of ARV treatment will be determined with reference to the WHO treatment 
guidelines if no country specific guidelines are available. Women who become pregnant 
and HIV positive during the trial will be referred for appropriate Prevention of Mother-to-
Child Transmission (PMTCT) services. 
 
The research centres will inform IPM Medical Safety of any new HIV infections within 48 
hours of diagnosis. The applicable regulatory authorities and ethics committees who 
require expedited notification of HIV seroconversion will be notified by either IPM or the 
research centre in accordance with standard operating procedures and policies of the 
regulatory authorities or ethics committees. 
 
5.5. Contraceptive Counselling and Management of Contraception  
Contraceptive counselling will be provided at all research centre visits. Counselling will 
be tailored per research centre, depending on local community and regional guidelines 
and will be detailed in research centre procedures. Counselling will include information 
about medication side effects and interactions, the importance of contraceptive 
adherence for the duration of the trial; what to do in the event of accidental non-
adherence and advice on how to remain adherent. 
 
Participants will also be counselled that if they become pregnant during the trial, they will 
immediately discontinue the IP and be referred to the local prenatal services for support 


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and further management of the pregnancy. Refer to Pregnancy Testing and 
Management below in Section 5.6. 
 
To meet eligibility criteria, unless postmenopausal with no history of menses for one year 
prior to screening, participants must be on an effective method of contraception prior to 
enrolment, have demonstrated adherence to her chosen method of contraception and 
have no significant resultant problems.  
 
In order to address challenges that participants may experience in consistently obtaining 
an effective method of contraception, research centres will provide participants with 
contraceptives from screening for the duration of the trial, if required. The contraceptives 
provided will be consistent with what is available locally. Alternatively, participants will be 
referred to the local family planning clinic or continue accessing contraception from local 
family planning clinics. Under supervision of the investigator or designated qualified 
personnel, enrolled participants may switch from one contraceptive method to another, if 
effective contraception is maintained. 
 
5.6. Pregnancy Testing and Management 
A urine pregnancy test will be performed at all scheduled trial visits, except for the Exit 
Visit, and can be performed additionally at unscheduled visits if any reason exists to 
suspect pregnancy or, in the event of a participant defaulting on her contraception, prior 
to recommencing contraception. 
 
If a potential participant tests positive for pregnancy during screening, she is not eligible 
to enrol in the trial, but will receive referrals to prenatal clinics or other appropriate 
facilities. 
 
A product hold will be implemented if a woman tests positive for pregnancy while on IP. 
Vaginal ring(s) will be retrieved from the participant, but the participant will not be 
withdrawn from the study. Protocol-specified visit schedule and procedures will continue 
except for IP-related procedures and other examinations if contra-indicated by 
pregnancy. The participant will be referred to a local prenatal clinic for medical services. 
The research centres will be asked to report all pregnancies to IPM within 48 hours of a 
positive pregnancy test or a confirmatory serum pregnancy test, if indicated. A 
confirmatory serum pregnancy test may be requested at the discretion of the investigator 
or a designated qualified member of the trial staff if reason exists to suspect a false 
positive urine pregnancy test. If the serum pregnancy test is negative, the investigator 
can consider recommencing use of the ring. If the participant indicates a change in 
pregnancy status or the participant’s clinical history indicates a change in her pregnancy 
status after the product hold (birth or termination), a urine pregnancy test may be 
performed. A confirmatory serum pregnancy test may be requested at the discretion of 
the investigator or a designated qualified member of the trial staff if reason exists to 
suspect a false positive urine pregnancy test. If the urine pregnancy test is negative, the 
investigator can consider recommencing IP. The participant must have a negative urine 
pregnancy test prior to re-introduction of IP, and should not be breast-feeding. A pelvic 
examination should be performed prior to re-introduction of IP. 
Women who become pregnant and HIV-positive during the trial will be referred for 
appropriate PMTCT services. 
 
 


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Should a participant have a positive pregnancy test in an instance where she was 
determined to be HIV-seropositive but could not be confirmed as HIV-infected, was 
discontinued from IP use and consented to continued participation in the trial without IP, 
she will be allowed to continue in the trial to allow for continued follow-up and evaluation 
of her HIV status until the Exit Visit according to the original enrolment date. 
 
The research centres will be required to provide quarterly updates on the progress and 
outcome of the pregnancy as well as the first year of life of the child for inclusion in the 
Sponsor maintained pregnancy registry. This requirement may vary, depending on 
country-specific regulations. 
 
5.7. Demographics and Medical History 
At the Screening Visit basic demographic information will be collected. A confidential 
master log of participants, with demographic and locator information will be maintained.  
 
At both the Screening and Enrolment Visits (pre-enrolment) relevant medical history will 
be obtained, including but not limited to history of STIs, gynaecological conditions, 
hospitalisations, surgery, allergies, any conditions requiring prescription or chronic 
medication, i.e. > 2 weeks in duration, and acute conditions occurring prior to enrolment. 
 
5.8. Physical Examination 
A general physical examination will be conducted at screening and the LPUV, and will 
include weight, vital signs (body temperature, pulse rate, respiration rate, blood 
pressure), and examination of skin, respiratory, cardiovascular, central nervous and 
abdominal systems, as well as an assessment of cervical and axillary lymph nodes. 
Height will be measured only at the Screening Visit. A symptom-directed physical 
examination will be conducted at any visit if clinically indicated. 
 
5.9. Pelvic Examination 
A pelvic examination will be performed at screening and LPUV, or at any visit if clinically 
indicated. On-trial examinations will be performed to assess safety, i.e., any local vaginal 
reactions. 
 
If the participant is menstruating on the day of a visit where pelvic examination is due, all 
procedures, including the pelvic examination can be conducted as per investigator and 
participant discretion. If this is not possible, the participant will be asked to return 2 days 
after completion of menstruation, within the window period of the visit. 
 
Any unexpected or abnormal vaginal bleeding should be investigated to identify the 
possible source. A follow-up pelvic examination should be performed to ensure 
resolution of the condition as indicated. 
 
5.10. Laboratory testing for safety assessments and urine dipstick analysis 
Safety laboratory assessments and urine dipstick analysis (microscopy only if clinically 
indicated) will be conducted at the screening visit, or any other trial visit if clinically 
indicated.  Blood specimens for laboratory testing (haematology and chemistry testing) 
will be obtained by venepuncture. Haematology will include a full blood count, 


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differential, and platelet count. Chemistry tests will include creatinine, AST and ALT. 
Details of blood volumes are specified in Appendix C. At the discretion of the investigator 
or designee, each potential participant may be retested once for safety laboratory tests 
during the screening period. 
 
Additional tests may be performed at the investigator’s discretion after discussion with 
the IPM Clinical Physician (or designee) based on symptomatology and clinical 
assessment of participants. Additional descriptive information regarding specimen 
collection and processing for all tests will be detailed in the SOM. 
 
All laboratory results will be reviewed by the investigator or appropriately qualified and 
trained trial staff as designated by the investigator, and documented on the original 
laboratory report itself. 
 
5.11. STI Testing and Management 
5.11.1. STI Testing 
Cervicovaginal samples will be collected for STI testing at screening and the LPUV, or 
any other trial visit if clinical indicated. All participants will be evaluated for Trichomonas 
vaginalis (TV), Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT). At 
screening, blood will be collected by venepuncture for Syphilis (RPR) testing (Blood 
volume specified in Appendix C). TPHA/TPPA testing will be performed if the RPR is 
reactive. 
 
Additional descriptive information regarding specimen collection to test for STIs and 
processing of all tests will be detailed in the Laboratory Manual, as part of the SOM. 
 
NOTE: Documentation will be made in applicable CRFs for all cervicovaginal samples 
obtained in the presence of cervicovaginal blood. 
 
The investigator or appropriately qualified and trained trial staff as designated by the 
investigator will review all results, including rapid and laboratory tests, and the review will 
be documented by the reviewer on the original laboratory report itself. 
 
5.11.2. STI Management 
All participants who present with STIs will be managed appropriately as clinically 
indicated at the research centre or referred to a local health facility, according to local 
STI Treatment Guidelines.  Cervicovaginal swabs may be collected from these 
participants, at the investigator’s discretion or when required by local standard of care. 
Aetiological management may be applicable following STI testing, according to the 
aetiological diagnosis. 
 
The Clinical Management of Genital Diagnoses will be detailed in the SOM for guidelines 
to determine whether the vaginal ring requires temporary or permanent removal and to 
provide guidance regarding follow up recommendations.  
 
5.12. Cervical Cytology 
A cervical cytology sample will be collected at the Screening Visit if not done within the 
previous year, or if the result was abnormal at the last point of testing. Further details will 


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be provided in the Laboratory Manual, as part of the SOM. 
 
Women with abnormal cytology findings will be referred for appropriate medical services 
based on local standard of care for management of abnormal cervical cytology. 
Research centres will implement these referral systems prior to trial start.  
 
5.13. Vaginal Ring Dispensing 
Vaginal rings will be dispensed at the Enrolment Visit and subsequent Trial Visits. In the 
event that a participant will be away and unable to attend one of the Trial Visits where 
new vaginal ring(s) would be dispensed, the investigator or designee could dispense 
additional ring(s) on a case-by-case basis. All such circumstances must be documented 
fully by the investigator as described in the IPM 032 SOM. If a participant requires an 
additional ring at a time other than when they are scheduled to receive one, they will be 
required to attend the clinic for an interim visit.  During the monthly trial visit period, the 
participants will be instructed to self-insert the newly-dispensed vaginal ring at the 
research centre and to remove the ring at the next scheduled visit. During the 3-monthly 
trial visit period, the participants should self-insert one ring during the trial visit and each 
of the two additional rings at monthly intervals until their next scheduled research centre 
visit. Vaginal ring bags will be provided to participants during the 3-monthly trial visit 
period for the storage of the used rings, together with instructions on the storage of the 
unused and used rings. 
 
During the 3-monthly trial visit period, optional vaginal ring dispensing and return 
arrangement will be made with participants who prefer not to have additional vaginal 
rings in their possession. These participants will be provided with the option to return 
used vaginal rings and to collect new rings at the research centres at time intervals 
suitable to them, provided that the intervals allow for new vaginal rings to be inserted 
monthly. Optional HIV rapid tests will be offered to participants during these interim visits 
and will be conducted according to the Trial Visits HIV algorithm (refer to Appendix B). 
Participants’ preference regarding the intervals for product dispensing and return will be 
documented in the source document and applicable CRFs. 
 
5.14. Vaginal Ring Insertion and Ring Removal 
At the Enrolment and Trial Visits, participants will insert the vaginal rings under research 
centre supervision. The participant will be instructed to thoroughly wash her hands, 
relax, and get into a comfortable position either standing with one foot on a chair, lying 
on her back with her knees up, or squatting. After opening the folds of skin around the 
vagina, she will gently squeeze the ring into an oval shape and push it upwards and 
backwards towards the back as far as it will go, thereby depositing the ring in the vagina. 
She will then be instructed to thoroughly wash her hands again. At all research centre 
visits during which a pelvic examination is performed, the participant will remove the ring 
prior to the examination. 
 
If the participant requests help with either removal or insertion of the vaginal ring, or after 
she has made several attempts to remove/insert the ring without success, trained trial 
staff may give assistance. Re-education of the participant on ring removal/re-insertion 
will be given. This will be noted in the source documents and applicable CRFs. 
Additional instructions about ring use will be provided in the SOM. 
 


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All rings that are removed will be inspected visually, and an assessment will be made by 
the principal investigator or designee as to whether the ring appears to have been used 
or not, together with a reason for the assessment. The rings should then be rinsed in 
running water, patted dry, placed in a ring return bag, and stored between 15°C and 
30°C until shipment to the analytical laboratory for testing of residual dapivirine amounts. 
 
5.15. Vaginal Ring Adherence Counselling 
At the Enrolment and Trial Visits, participants will receive vaginal ring adherence 
counselling, including adherence to trial visit schedule and requirements. At the 
Enrolment Visit, participants will be provided with feedback on the IPM 027 and MTN-
020 trials, which will include information on trial adherence trends, as part of the vaginal 
ring adherence counselling. Research centre staff will counsel participants to refrain from 
removing the ring (except as directed during research centre visits) and will provide 
instructions to all participants in case of accidental ring expulsion (e.g., during sex or 
exercise), or removal, and guidance will be provided on how the ring should be handled 
when it is out of the vagina. Research centre staff will also provide instructions to the 
participants during the 3-monthly trial visit period for insertion of a new ring after a month 
and the participants will be counselled on how to store the used and unused rings at 
home, if applicable.  
 
If, for any reason, the participant is non-adherent to the use of the vaginal ring (i.e. she 
removes the ring for any purpose other than as instructed at a trial visit), this should be 
documented according to the guidelines specified in the SOM.  
 
5.16. Participant Questionnaire 
The Participant Questionnaire will be administered at every trial visit and the LPUV. This 
questionnaire includes acceptability questions about the monthly and 3-monthly 
research centre follow-up during the trial. 
 
5.17. Sample Storage and Analysis 
Blood (blood volume as specified in Appendix C) and vaginal fluid samples will be 
collected for storage locally or at a central laboratory at all research centre visits. Blood 
samples for HIV viral genotype resistance testing and HIV-1 RNA PCR will be stored at 
the Screening Visit, the Enrolment Visit, every Trial Visit, LPUV and Exit Visit and will be 
tested subsequent to confirmed HIV-1 seroconversion, according to the HIV testing 
algorithm described in Section 5.4. Testing will also be conducted on a random sample 
of HIV-negative participants. For possible dapivirine concentration measurements, 
plasma and vaginal fluid samples should preferably be collected prior to removal of the 
vaginal ring. Further details regarding these procedures will be provided in the 
Laboratory Manual, as part of the SOM. 
 
All specimens will be collected and analysed according to methods described in the 
Laboratory Manual and research centre SOPs for proper collection, processing, 
labelling, and transport of specimens to the laboratories conducting the analysis. Where 
possible and appropriate, stored specimens will be re-tested to assess validity of 
unusual or unexpected assay results. 
 
 


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Any residual specimens will be destroyed at the end of the trial after all protocol-required 
and quality control testing has been completed. 
 
5.18. Screening Identification (SCR-ID) and Participant Identification (PID) 
Numbers 
After informed consent is obtained, a SCR-ID number will be assigned to each 
participant for identification purposes and the participant will be screened to assess 
eligibility for the trial. As each new participant enters the trial, a unique PID number will 
be assigned in consecutive order, starting with the lowest number available at the 
research centre at the time. 
 
5.19. Diary cards 
Participants will be provided with diary cards at enrolment and at trial visits, as 
applicable, except the LPUVs and Exit Visits. The diary cards are meant to be completed 
by the participants, and returned to the research centre at each Trial Visit and the LPUV 
to serve as a memory aid for participants to review during their scheduled visits and 
adherence counselling. The diary card will be used to document the removal and 
insertion date of the additional rings and for documenting AEs experienced and 
concomitant medications taken between trial visits. Participants will be requested to 
document the details of all cases of accidental ring expulsion or removal. Additional 
instructions on diary cards will be provided in the SOM. 
 
5.20. Reimbursement 
Participants will be reimbursed for any travel costs incurred in compliance with local 
regulations. Reimbursements will be made after the completion of each trial visit. 
Research centre specific reimbursement amounts will be documented in the trial ICF 
approved by the applicable IRB/IEC. Upfront reimbursement for travel expenses may be 
made if this has been approved by the relevant ethics committee. 
Note: During the 3-monthly trial visit period, participants who choose to not receive the 
two additional vaginal rings during trial visits, will be responsible for the travel costs 
incurred during the optional vaginal ring collection/return visits to the research centre. 
 
5.21. Participant Compensation 
If a participant in an IPM clinical trial becomes ill or injured as a result of participation in 
the trial, medical treatment for the adverse reaction or injury will be provided 
appropriately. The research centre staff will refer the participant for ongoing treatment for 
the injury, if needed. The Sponsor will be responsible for compensation for appropriate 
medical expenses for treatment of any such illness or injury. An HIV infection that occurs 
during the course of the trial will not be considered an injury or illness caused by trial 
participation. 
 
5.22. Participant Responsibility 
Referral systems to local medical services will be implemented by research centres prior 
to trial start. It remains the participant’s responsibility to follow up with relevant medical 
services once referral has been initiated by the research centre. 


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5.23. Study Operations Manual (SOM) 
A SOM will be supplied to all research centres to provide general guidance on the 
conduct of trial procedures. The Laboratory Manual is contained within the SOM. 
6. Investigational Product  
6.1. Investigational Product Composition 
The dapivirine silicone elastomer vaginal matrix ring is an off-white flexible ring 
containing 25 mg of dapivirine dispersed in a platinum-catalysed silicone matrix. The 
dimensions of the ring are 56 mm (outer diameter) and 7.7 mm (cross sectional 
diameter). The dapivirine silicone elastomer vaginal matrix ring is designed to provide 
sustained release of dapivirine over a minimum of one month. 
 
The Dapivirine Vaginal Ring-004 is comprised of dapivirine, the polydimethylsiloxane 
liquid MED-360 and the silicone MED-4870. The safety of dapivirine has been 
established in a comprehensive nonclinical and clinical development programme 
described in the IB5. Both the silicone elastomers and the liquid silicone dispersant have 
been evaluated in in vitro cytotoxicity, haemolysis tests, cytogenic damage and 
genotoxicity assays, and in in vivo systemic toxicity studies, intracutaneous toxicity 
studies, pyrogen studies and delayed contact sensitisation studies. The silicone 
elastomer was also evaluated in muscle implantation studies of up to 12 weeks duration. 
In addition, a number of preclinical tests were performed on the finished Dapivirine 
Vaginal Ring-004, including a panel of biocompatibility tests (in vitro cytotoxicity and 
genotoxicity assays, and in vivo vaginal irritation and sensitisation studies) using extracts 
of the ring, and a study in sheep, in which Dapivirine Vaginal Ring-004 containing 25 mg 
dapivirine was inserted into the vagina (up to 3 consecutive rings; each ring for a period 
of 30 days). None of these tests identified any significant safety concerns. 
 
6.2. Packaging and Labelling 
IPM will bear the responsibility for primary and secondary packaging and labelling. The 
packaged rings will be labelled according to local regulatory requirements. 
 
6.3. Investigational Product Storage 
The recommended storage condition for the dapivirine ring is 15°C to 30°C, excursions 
permitted. The proposed shelf life is 48 months when stored in the original packaging 
under the recommended storage conditions. In the event that the IP has been subjected 
to different storage conditions than specified above, the affected IP will not be used 
(unless IPM or its designee provides written authorisation for use). IPM should be 
notified immediately in the event that IP storage conditions have been breached. 
 
The investigator (or pharmacist) will maintain an inventory and acknowledge receipt of all 
shipments of IP. More information on IP storage will be provided in the SOM. 
 
Participants will be provided with instructions on storage of used and unused rings 
during the 3-monthly trial visit schedule. 
 


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6.4. Investigational Product Administration  
The participants will be instructed to self-insert the Dapivirine Vaginal Ring-004 at the 
Enrolment Visit, and monthly thereafter. The participants will be reminded of proper 
vaginal ring insertion and removal procedures.  
 
During the 3-monthly trial visit schedule, participants will be instructed to remove the 
vaginal rings and self-insert each of the two additional rings at monthly intervals until 
their next scheduled research centre visit. The self-insertion and removal of the rings 
should take place at the research centres during the months that the participants attend 
their scheduled trial visits.  Participants should be advised to continue ring use through 
menses. 
 
6.5. Investigational Product Expulsion or Loss 
If a participant accidentally expels the ring, e.g., during sex or exercise, she will be 
instructed to rinse the vaginal ring thoroughly in clean water and re-insert the ring as 
soon as possible. If the vaginal ring is expelled and cannot be successfully reinserted, 
the ring should be appropriately rinsed, patted dry and stored in the bag provided for this 
purpose, until the earliest possible opportunity the participant can return for help with the 
reinsertion of a ring at the research centre.  
 
During monthly visits, if the ring is expelled in such a manner that the participant is 
unwilling to re-insert it, e.g., during urination or a bowel movement, or if the ring is lost, 
the participant should return to the research centre at the earliest possible opportunity to 
receive a replacement ring.  
 
During the 3-monthly trial visit schedule, participants will be instructed that if the ring is 
expelled in such a manner that the participant is unwilling to re-insert it, e.g., during 
urination or a bowel movement, or if the ring is lost, the participant should use one of the 
unused, additional rings dispensed. If the expelled ring was the last of the additional 
vaginal rings dispensed, the participant should return to the research centre at the 
earliest possible opportunity to receive a replacement ring.  
 
Also, in cases where a ring is removed due to a genital infection, a new ring will be 
inserted or dispensed. Visits associated with expulsion or loss of rings will be regarded 
as unscheduled visits unless the visit is within the 7-day window period of the next 
scheduled visit. 
 
6.6. Retrieval of Investigational Product 
All participants who are prematurely discontinued from the trial will be encouraged to 
return to the research centre for a final evaluation, at which time all vaginal rings in the 
participant’s possession should be retrieved. If the participant does not return her used 
or unused vaginal ring at this visit, it should be retrieved as soon as possible after this 
visit, either by the participant returning it to the trial staff, or by trial staff conducting a 
home visit. 
 
For participants who are considered lost to follow-up and permanently discontinued from 
the trial, reasonable contact attempts will be made according to the locator information 
provided by the participant and local SOPs. Any used or unused vaginal rings that could 
not be retrieved will be documented in the source documents and applicable CRFs. 


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6.7. Investigational Product (IP) Accountability 
The principal investigator or designee will be responsible for adequate and accurate 
accounting, handling, storage and dispensing of the IP. The IP will be stored safely and 
properly in a secure location with access available only to the principal investigator and 
designated trial personnel. IP and clinical supplies are to be dispensed only in 
accordance with the protocol. Accurate records of IP received from IPM, the amount 
dispensed to the participants, the amount returned by the participants, the quantity 
remaining at the conclusion of the trial and any wasted or expired IP will be maintained. 
 
Unused and used rings not analysed for residual amounts of dapivirine will be destroyed 
according to IPM instruction and local regulatory requirements. 
 
6.8. Concomitant Medications and Products 
Prescription and non-prescription medications will be recorded on the source documents 
and applicable CRFs. Vaginal products and practices including the use of spermicides, 
intravaginal medication, douches, lubricants, tampons and female condoms may be 
used during the trial and will be captured. Further details will be provided in the SOM. 
7. Adverse Events 
7.1. Definition 
An AE is any untoward medical occurrence during the course of a trial in a participant 
who received an IP at any dose, which does not necessarily have a causal relationship 
with the IP. An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom or disease temporally associated with the use of 
an IP, whether or not considered related to the IP. This definition includes inter-current 
illnesses or injuries and exacerbation of pre-existing conditions. 
 
An unexpected adverse event is an adverse event, the nature or severity (intensity) of 
which is not consistent with the applicable product information (i.e. IB, package insert, or 
summary of product characteristics). Final determination of whether an event is 
considered unexpected will be made by the Sponsor, however, the investigator should 
be knowledgeable of the contents of the IB. 
 
Whenever possible, the laboratory abnormalities should be considered in the context of 
the primary clinical diagnosis and should be reported as such (e.g. acute hepatitis with 
increased bilirubin). Clinically significant laboratory abnormalities will be considered AEs 
and graded for severity based on the Division of AIDS (DAIDS Table for Grading 
Severity of Adult and Pediatric Adverse Events) as appropriate. 
 
Any condition occurring prior to enrolment will be reported as a pre-existing condition 
under Medical or Gynaecological History. All AEs occurring during the trial will be 
recorded in the source documents and applicable CRFs.  All AEs will be reported and 
graded according to the latest version of the DAIDS Table for Grading Severity of Adult 
and Pediatric Adverse Events and Female Genital Grading Table for Use in Microbicide 
Studies (which will be provided to research centres in the SOM). A vaginal bleeding 
abnormality thought to be due to contraception, asymptomatic BV and asymptomatic 
candidiasis will not be reported as an AE for this trial. 
 


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If a unifying diagnosis is possible, the investigator should record a specific disease or 
syndrome rather than individual associated signs and symptoms. However, if an 
observed or reported sign, symptom, or clinically significant laboratory abnormality is not 
considered a component of a specific disease or syndrome by the investigator, it should 
be recorded as a separate AE. 
 
All AEs will be monitored until resolution and/or the cause are identified, or until the 
investigator does not expect any improvement or worsening of condition/symptoms. If a 
SAE, urogenital AE or related AE remains unresolved at the participant’s Exit Visit, the 
research centre investigator will make a clinical assessment with the IPM Clinical 
Physician to determine whether continued follow-up of the AE is warranted. All other AEs 
that are not serious, not urogenital and assessed to be unrelated to IP will be noted as 
ongoing at trial end if the outcome is not yet determined at the time of the exit visit. 
 
7.2. Assessment of Adverse Event Severity 
The investigator is responsible for assessing the severity of AEs occurring on trial. All 
AEs except genital complaints will be graded according to the latest version of the 
DAIDS Table for Grading Severity of Adult and Pediatric Adverse Events. All genital 
complaints will be graded according to the latest version of the Female Genital Grading 
Table for Use in Microbicide Studies, which will be provided to research centres in the 
SOM. 
 
For AEs not listed on either of these tables, the following criteria will be used to estimate 
the grade of severity: 
• 
Mild 
Symptoms causing no or minimal interference with usual social and functional 
activities 
• 
Moderate 
Symptoms causing greater than minimal interference with usual social and 
functional activities 
• 
Severe 
Symptoms causing inability to perform usual social and functional activities 
• 
Potentially Life-threatening 
Symptoms causing inability to perform basic self-care functions OR medical 
or operative intervention indicated to prevent permanent impairment, 
persistent inability, or death 
 
7.3. Relationship to Investigational Product 
The investigator is responsible for determining the relationship of all AEs occurring 
during the trial and will assess AEs based on the following criteria: 
• 
Not Related 
There is not a temporal relationship or a reasonable possibility of a causal 
relationship (i.e. some level of evidence is lacking) to administration of the 
investigational product. The AE is clearly explained by another cause 
(concurrent disease, concomitant medication, environmental or toxic factors, 


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etc.). 
• 
Related 
There is a reasonable possibility of a causal relationship between the 
investigational product and the AE, (i.e. there is some level of evidence as to 
the causal association). The event may respond to withdrawal of the 
investigational product (dechallenge), and recurs with rechallenge by 
administration of the investigational product. In other cases the AE is clearly 
related and most likely explained by the administration of the investigational 
product. 
 
7.4. Serious Adverse Event 
7.4.1. Serious Adverse Event Definition 
A serious adverse event (SAE) or reaction is any untoward medical occurrence that at 
any dose: 
• 
Results in death. 
• 
Is life-threatening. 
This criterion applies if the participant is at immediate risk of death from the 
event as it occurred, in the opinion of the investigator; it does not refer to an 
event which hypothetically might have caused death if it were more severe. 
• 
Requires in patient hospitalisation or prolongation of existing 
hospitalisation. 
This criterion applies if the event requires inpatient hospitalisation and results 
in an overnight stay in hospital or, if in the opinion of the investigator, 
prolongs 
an 
existing 
hospitalisation. 
A 
hospitalisation 
(including 
hospitalisation for an elective procedure or routinely scheduled treatment not 
associated with an adverse event) for a pre-existing condition which has not 
worsened does not constitute an SAE. 
• 
Results in persistent or significant disability/incapacity. 
This criterion applies if the event causes a substantial disruption of a person’s 
ability to conduct normal life functions. 
• 
Is a congenital anomaly/birth defect. 
This criterion applies if a participant gives birth to a child with a congenital 
anomaly or birth defect or if the anomaly/birth defect is diagnosed by any 
prenatal tests. 
• 
Important medical events (medically significant) that may not be 
immediately life-threatening or result in death or hospitalisation but may 
jeopardize the participant or may require intervention in order to prevent one 
of the outcomes listed above should also be considered serious; e.g., 
bronchospasm requiring intensive treatment in an emergency room or at 
home. 
NOTE: A SAE does not have to be severe in nature to meet any of the above criteria. 
 
 
 
 


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All SAEs that occur from the time the participant is enrolled through the duration of the 
trial, whether considered associated with the IP or not, must be reported to the IPM 
Medical Safety Physician and/or designee within 24 hours of the centre becoming aware 
of the event. All SAEs should be recorded in the source documents and the relevant 
CRFs and reported using the Immediately Reportable Events (IRE) Form provided. 
 
The IRE Report Form should be completed with all the available information at the time 
of reporting. The investigator is required to write a detailed report and complete SAE 
follow up in a timely manner until the SAE has resolved, the participant returns to normal 
health, or until the investigator does not expect any further improvement or worsening of 
the condition. Medical Records may be requested by IPM to assist in assessing 
relatedness and severity of the SAE, and for possible submission to the Regulatory or 
Health Authorities as appropriate. To maintain confidentiality, the participant’s name 
must be blacked out on any medical records submitted and replaced with the PID 
number and the initials. 
 
More details on SAE reporting requirements and processes are described in the Safety 
Reporting Plan (provided in the SOM) provided to the research centres. 
 
7.4.2. Serious Adverse Event Contact Information 
 
SAEs will be reported to IPM or designee within 24 hours of any research centre staff 
member becoming aware of the event. If the SAE is related, and life-threatening or fatal, 
IPM Medical Safety should additionally be notified immediately by email or telephone. 
 
The following email will be used for communication with the IPM Medical Safety team 
regarding any IREs: safetyreports@ipmglobal.org. Contact details of relevant safety 
personnel will be provided in the Safety Reporting Plan. 
 
IPM will process all safety events. The IPM Medical Safety Physician will review all SAEs 
and generate the necessary queries. Further SAE reporting guidelines will be specified 
in the Safety Reporting Plan. 
 
7.4.3. Sponsor Notification of SAEs to the Regulatory Agencies 
Any unexpected serious adverse events which are deemed related to investigational 
product, will be considered “associated with the use of investigational product” and, as 
such, IPM will notify the appropriate regulatory authorities of the event in an expedited 
manner unless policies of the local regulatory authorities mandate such reporting by the 
research centre.  
 
Any unexpected SAE deemed to be unrelated to the IP will not be reported to the 
regulatory authorities in an expedited manner, unless policies of the local regulatory 
authorities mandate such reporting. 
 
7.4.4. Research Centre Notification of SAEs to Local Independent Ethics 
 Committee or Local Health and Regulatory Authorities 
The investigator will report all SAEs to the local IEC and/or regulatory or health 
authorities in accordance with standard operating procedures and policies of the IEC 
and/or regulatory or health authorities. 


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7.5. Immediately Reportable Events 
These are events which, while not necessarily meeting criteria for seriousness, are 
considered important by IPM and as such warrant immediate reporting to IPM. The 
following events should be reported to the Sponsor within 48 hours of any research 
centre staff member becoming aware of the event: 
• 
Pregnancy: Although not considered an AE, pregnancy must be reported if it 
occurs at any time while on IP during the trial;  
• 
HIV infection any time during the trial;  
• 
Any non-serious AE (including laboratory abnormalities) leading to permanent 
discontinuation of the investigational product.  
 
All IREs that occur from the time the participant is enrolled should be reported to IPM 
within the time periods specified above. All IREs should be recorded in the source 
documents and the relevant CRFs and should be reported to the IPM Medical Safety 
Physician using the IRE Form provided. 
 
As with SAEs, the IRE form should be completed with all available information at the 
time of reporting. The investigator is required to follow up the IRE in a timely manner 
until such time as it is deemed appropriate by IPM that all relevant information has been 
collected, or until such time as the participant is lost to follow up. 
 
7.6. Safety Monitoring 
The IPM 032 trial team will monitor safety and participant recruitment throughout the trial 
for all participants.  
 
7.7. Data Handling at Research Centres 
All trial data will first be collected on designated source documents and then recorded on 
CRFs with the exception of the Participant Questionnaire, for which the CRFs will serve 
as the source document, unless otherwise specified by IPM. Research centre staff 
responsible for completing the CRFs will receive appropriate training prior to the start of 
the trial, and will follow standardised procedures. Data must be legibly entered onto the 
CRFs. Data corrections will be made in accordance with standard procedures provided 
by IPM or its designee. Instructions for CRF completion will be provided on the back of 
the CRF pages, as well as in the SOM.  
 
The investigator will maintain, and store in a secure manner, complete, accurate and 
current trial records throughout the trial. Standard GCP practices will be followed to 
ensure accurate, reliable and consistent data collection. 
 
7.8. Source Data Verification 
All trial data must be verifiable to the source documentation (which includes original 
recordings, laboratory requisitions and reports, medical records, etc.). Source 
documentation will be made available to the IPM or representative(s) for review to 
ensure that the collected data is consistent with CRFs and has been completely and 
accurately reported as required by the trial protocol. 


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8. Statistical Methods  
IPM 032 is a Phase IIIb, multi-centre, open-label follow-on trial to IPM 027 to evaluate 
the safety of and adherence to Dapivirine Vaginal Ring-004, inserted at monthly intervals 
in healthy, HIV-negative women who have participated in the IPM 027 trial.  
 
Individuals meeting all inclusion criteria and no exclusion criteria will be eligible to 
receive the Dapivirine Vaginal Ring-004 with monthly research centre follow-up for one 
month (which may be extended to three months  at the investigator’s discretion) followed 
by  3-monthly research centre follow-up visits.  
 
Approximately 1400 participants are expected to be enrolled in the trial. 
 
Participants will self-insert the vaginal rings. Once participants commence the period of 
3-monthly follow up visits, two additional rings will be dispensed at each trial visit, the 
first of which the participants should self-insert one month later, and the second ring one 
month after that, before returning to the research centre for their next scheduled visit.  
 
An exit visit will be conducted 1-2 months after removal of the last ring (last product use 
visit).  
  
8.1. Trial Endpoints  
The primary and secondary trial endpoints are described in detail in Section 2.2 of the 
protocol. 
 
8.2. Primary Trial Hypotheses 
From previous clinical and safety trials of dapivirine, there is reason to believe that the 
Dapivirine Vaginal Ring-004 is safe and well tolerated. Thus, it is hypothesised that the 
Dapivirine Vaginal Ring-004 will be safe and well tolerated in healthy HIV-negative 
women over a 12-month period of exposure.  
 
8.3. Sample Size and Power Calculations 
This trial will be conducted in healthy, HIV-negative women who have participated in the 
IPM 027 trial. No formal sample size or power calculations have thus been performed. 
 
It is expected that approximately 70% of the participants enrolled in IPM 027 will 
participate in this trial. Therefore, a total sample size of approximately 1400 HIV-negative 
women is anticipated.  
 
8.4. Statistical Analyses 
The primary analysis will focus on safety as well as adherence assessments.  
 
The primary analysis will be performed under the intent-to-treat (ITT) principle, which will 
include all participants enrolled in the trial.  As it is possible that the inclusion of non-
adherent participants or participants who discontinued from the IP may artificially lower 
the rates of safety outcomes, additional analyses will be conducted on the per-protocol 
population, which will include only participants who were adherent to the protocol. 
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used to examine the exploratory objectives and other technical aspects of these 
analyses will be provided in a SAP, which will be finalised prior to final database lock. 
 
The analysis of the secondary safety assessments will be mainly descriptive in nature. 
The incidence density rate of HIV-1 seroconversion and the frequency of HIV-1 drug 
resistance in women who seroconvert will be summarised descriptively.   
 
The data will be presented using appropriate statistical measures including, but not 
limited to: mean, standard deviation, median, and interquartile range for continuous data; 
frequency and relative frequency for categorical data. When appropriate, 95% 
confidence intervals will be presented.       
 
8.4.1. Primary Safety Analysis 
A descriptive analysis of all AEs will be presented in tables and listings. AEs will be 
summarised by MedDRA System Organ Class (SOC) and Preferred term (PT). The 
proportion of participants experiencing adverse events, including the proportion of 
participants experiencing product-related adverse events, Grade 3 or 4 AEs, or SAEs, 
will be determined, and presented with corresponding 95% CIs.  
All data will be presented by research centre, and overall across research centres.  
 
8.4.2. Primary Adherence Analysis 
Residual levels of dapivirine in returned rings and/or plasma and/or vaginal fluid 
concentrations of dapivirine will be used as measures of adherence to ring use. The data 
will be listed, summarised and presented graphically. Participants will be categorized as 
either adherent or non-adherent, based on these measures. The ring residual levels 
and/or plasma and/or vaginal fluid concentrations of dapivirine associated with non-
adherence will be informed by the results from IPM 027, and will be described in detail in 
the SAP, which will be finalised prior to final database lock.  The correlation between the 
amount of residual dapivirine in the used rings and the corresponding plasma and/or 
vaginal fluid levels of dapivirine will be explored graphically and summarised 
descriptively.  
 
8.4.3. Secondary Analyses 
 
Incidence of HIV-1 seroconversion 
The incidence of HIV-1 seroconversions, the incidence density rate of HIV-1 
seroconversion, i.e. HIV-1 seroconversion rate per 100 woman-years of product use at 
the end of the ring use period, as well as a 95% CI for the HIV-1 seroconversion rate per 
100 woman-years based on the normal approximation of the Poisson distribution will be 
presented for each research centre, and overall. Kaplan-Meier curves will be presented, 
stratified by research centre.  
 
 
HIV-1 drug resistance 
The analysis of HIV-1 drug resistance will be primarily descriptive in nature, and will 
depend on the pattern of resistance mutations observed in the HIV-1 seroconverters.  
The resistance associated mutations observed will be listed by participant, and a 
frequency tabulation of individual resistance mutations associated with the various 


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classes of antiretrovirals, e.g. Protease Inhibitors, Nucleoside Reverse Transcriptase 
Inhibitors and Non-nucleoside Reverse Transcriptase Inhibitors, will be produced. The 
proportion of HIV-1 seroconverters with at least one HIV-1 drug resistant mutation will be 
presented, with the corresponding 95% CI. 
 
8.4.4. Interim Analysis 
No interim analysis is planned for this trial. However, the Sponsor will review the 
treatment emergent safety data at regular intervals during the conduct of the trial.  
 
8.5. Data and Safety Monitoring Board 
This clinical trial will not be subject to DSMB overview. 
 
8.6. Handling of Missing Data and Dropouts 
Some degree of missing data, primarily associated with missed visits, is expected. The 
amount of missing data will be explored and incorporated into the analyses, where 
appropriate. For the analysis of adherence to monthly ring use, patterns of missing data 
may be informative. Depending on the proportion of participants who discontinue early, 
an analysis of time to discontinuation may be conducted. Such an analysis would allow 
investigation of the covariates associated with early discontinuation and could provide 
information that would be useful in designing future trials of other microbicide rings. 
Patterns of missing data may also provide further insight into participants’ preference for 
monthly or 3-monthly follow-up visits to research centres. 
9.  Investigator Requirements 
9.1. Trial Initiation 
The trial can be initiated at the research centre once all relevant IRB/IEC and regulatory 
approvals have been obtained in compliance with country specific requirements, and the 
relevant essential documents are available on file. Following IPM approval, IPM will 
notify the research centre in writing via letter correspondence to begin trial operations 
according to the protocol. 
 
9.2. Institutional Review Boards or Independent Ethics Committee Approval 
This protocol, the informed consent document, and relevant supporting information will 
be submitted to the IRBs/IECs for review and must be approved before the trial is 
initiated. 
 
The principal investigator is responsible for communicating with IRBs/IECs regarding the 
progress of the trial and changes made to the protocol as deemed appropriate, at least 
once a year. The principal investigator will also keep the IRBs/IECs informed of any 
significant AEs and SAEs, in accordance with standard operating procedures and 
policies of the IRB/IEC. 
 
 


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9.3. Trial Monitoring and Audits 
Trial monitors will regularly visit participating research centres to review trial documents 
including, but not limited to individual participant records, consent forms, source 
documents, CRFs, supporting data, laboratory specimen records and medical records 
(physicians’ progress notes, nurses’ notes, individuals’ hospital charts) to ensure 
protection of trial participants, compliance with the protocol, and accuracy and 
completeness of records. The trial monitors will also inspect the research centre’s 
regulatory files to ensure that regulatory requirements are being followed; the research 
centre’s pharmacies to review product storage, management, and drug accountability; 
and the research centre’s laboratory and other clinical supplies to ensure proper storage 
and continued viability of supplies. All applicable trial documents should be readily 
available for review during the visits. The trial monitors will also check that clinical trial 
procedures are observed and will discuss any problems with investigator or designee as 
applicable. 
 
During or after the clinical trial, the governmental regulatory authorities, local IRB/IEC 
and/or representatives of the IPM may request access to all trial documents for on-
research centre audit or inspection. 
 
9.4. Case Report Forms (CRFs) 
CRFs will be supplied by IPM or its designee and will be handled in accordance with 
instructions from IPM. 
 
All CRFs will be completed by the designated trial staff in accordance with the 
instructions provided by IPM. Upon trial completion, the CRF is reviewed, signed, and 
dated by an investigator listed on the Statement of Investigator, Form FDA 1572. 
 
All CRFs will be completed in a neat, legible manner to ensure accurate interpretation of 
data. Black ink is required to ensure clarity. When making changes or corrections, the 
original entry will be crossed out with a single line, and the change initialled and dated. 
Erasures, overwriting, and correction fluid are NOT allowed on the CRFs. 
 
9.5. Disclosure of Data 
Participant medical information is confidential and disclosure to third parties other than 
those described in Section 9.3 is strictly prohibited. All trial data will be stored securely at 
the research centre. All participant information including laboratory reports, forms, lists, 
logbooks, appointment books and administrative forms will be stored in locked file 
cabinets or rooms in areas with access limited to trial staff. 
 
Participants’ trial information will not be released without written permission of the 
participant, except as necessary for monitoring by the Sponsor, Sponsor’s designated 
monitors, regulatory authorities, or local IRBs/IECs. 
 
9.6. Record Retention 
The principal investigator will retain in a secure manner, complete, accurate and current 
trial records for a minimum of two years after marketing approval or termination of 
product development. Trial records include administrative documentation, including 
research centre registration documents and all reports and correspondence relating to 


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the trial, as well as documentation related to each participant screened and/or enrolled in 
the trial, including ICFs, CRFs, notations of all contacts with the participant, and all other 
source documents. All records must be retained on-site throughout the trial’s period of 
performance. IPM will provide the research centre with written instructions for long-term 
record storage at the completion of the trial. 
 
No records should be destroyed without prior written permission from IPM. 
10. Ethical Considerations 
10.1. Ethical Review 
This protocol, research centre-specific informed consent documents, participant 
education, outreach, recruitment materials and any other requested documents or 
subsequent modifications will be reviewed and approved by the ethical review bodies 
responsible for oversight of research conducted at the research centre. 
 
Subsequent to initial review and approval, the local IRB and/or IEC will be notified about 
trial completion within three months following trial termination or completion. This trial will 
be conducted in accordance with: 
• 
World Medical Association Declaration of Helsinki8 
• 
ICH GCP guidelines9 
• 
Applicable national ethics and regulatory requirements in countries where the 
trial is being conducted, e.g. Guidelines for Good Practice in the Conduct of 
Clinical Trials in Human Participants in South Africa10. 
 
10.2. Reporting and Management of Social Harms related to trial participation 
Social harms, e.g., disruption of family or personal relationships may result due to 
participation in this trial becoming known to others. In addition, IP use could potentially 
be unacceptable to the participant’s sex partner and result in difficulties with her sex 
partner. If a participant is or becomes HIV-infected, she may also experience social 
harms. 
 
During each HIV counselling session, enrolled participants will be asked questions to 
assess the occurrence of social harms related to trial participation. Participants who 
experience social harms considered to be related to trial participation will be counselled 
accordingly and provided with assistance to mitigate the circumstances if possible. This 
will be recorded in the source documents and applicable CRFs. 
 
10.3. Community Engagement 
Community Liaison Officers have been appointed at each research centre to oversee the 
information provided to local stakeholders, target population and general community. 
They have been tasked with capturing, monitoring and evaluating feedback from the 
community. Comments will be captured in various ways at each research centre using 
methods such as suggestion boxes, door-to-door campaigns, group level discussions, 
pre/post-tests, distributed feedback forms, etc. Each research centre has a process for 
consulting with the community. The primary vehicle for this consultation is through formal 
structures such as the Community Advisory Boards/Groups/Committees. These systems 


IPM 032 
 
   22 October 2015 
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allow investigators and communities to identify and respond rapidly to concerns raised. 
11.  Publications 
Any presentation, abstract, or manuscript shall be reviewed and approved by the 
Sponsor prior to submission. Publication of the results of this trial will be governed by the 
IPM’s clinical trial agreement with the investigator.  Authorship criteria will be based on 
contributions to the design, work, and analysis of the trial. 
 
 
 


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12. References 
 
 
1 Regional Fact Sheet 2012. Sub-Saharan Africa. 
http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2012/gr2
012/2012_FS_regional_ssa_en.pdf 
 
2 AIDS by the numbers; UNAIDS 2013. 
http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspublication/201
3/20131120_AIDSbynumbers_A5brochure_en.pdf 
 
3 Elias CJ, Coggins C. Female-controlled methods to prevent sexual transmission of 
HIV. AIDS 1996;10:S43-S51. 
 
4 Karim SSA, Richardson BA, et al. Safety and effectiveness of BufferGel and 0.5% 
PRO2000 gel for the prevention of HIV infection in women. AIDS 2011; 25(7):957. 
 
5 Dapivirine Vaginal Ring Investigator’s Brochure, Version 9.0, 3 December 2014  
 
6 IPM 011; Clinical Study Report;  Version 1.0, 15 March 2011 
 
7 IPM 015; Clinical Study Report;  Version 1.0, 06 July 2012 
 
8 World Medical Association Declaration of Helsinki. Ethical Principles for Medical 
Research Involving Human Subjects; WMA General Assembly, Fortaleza, Brazil, October 
2013. Available at:  http://www.wma.net/en/30publications/10policies/b3/index.html 
 
9 Guidance for Industry: E6 Good Clinical Practice: Consolidated Guidance. 
 (http://www.fda.gov/downloads/Drugs/Guidances/ucm073122.pdf) 
 
10 Guidelines for Good Practice in the Conduct of Clinical Trials in Human Participants in 
South Africa. 
(http://www.kznhealth.gov.za/research/guideline2.pdf) 
 
 


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APPENDIX A: SCHEDULE OF PROCEDURES 
Visits 
Screening 
Enrolment 
Trial Visits 
LPUV 
Exit Visit 
As needed 
Trial Months 
Screening 
must occur 
within 45 
days of 
enrolmentk 
0 
 Months 1-11h,i 
Month 12i 
Months 13-
14i 
Informed Consent 
X 
 
 
 
 
 
Comprehension Assessment 
X 
 
 
 
 
 
Assign Screening Identification Number 
X 
 
 
 
 
 
Assign Participant Identification Number  
 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Medical History 
X 
X 
 
 
 
 
Concomitant Medication Evaluation 
X 
X 
X 
X 
X 
X 
Inclusion/Exclusion Criteria  
X 
X 
 
 
 
 
Locator Information 
X 
X 
X 
X 
 
 
Basic Menses Information 
X 
X 
X 
X 
 
 
Physical Examination 
X 
 
 
X 
 
X 
Adverse Event Evaluation 
 
X 
X 
X 
X 
X 
Social Harms Assessment 
 
X 
X 
X 
X 
X 
Pelvic Exam 
X 
 
 
X 
 
X 
Vaginal Ring Dispensing and Insertion 
 
X 
X 
 
 
 
Vaginal Ring Return / Collection 
 
 
X 
X 
 
 
Visual  Inspection of Returned Ring(s) 
 
 
X 
X 
 
 
Provision of Vaginal Ring Use and Storage Instructions 
 
X 
X 
 
 
 
Vaginal Ring Adherence Counselling 
 
X 
X 
 
 
 
Provision of Diary Card(s) 
 
X 
Xj 
 
 
 
Collection of Diary Card(s) 
 
 
X 
X 
 
 
Participant Questionnaire 
 
 
Xa 
X 
 
 
HIV/STI Risk Reduction Counselling 
X 
X 
X 
X 
X 
 
Contraceptive Counselling 
X 
X 
X 
X 
X 
X 
Provision of and/or referral for Contraceptives 
X 
X 
X 
X 
X 
X 
Provision of Male Condoms (if participant wishes to 
receive them) 
X 
X 
X 
X 
X 
 
Urine Pregnancy Test (hCG)  
X 
X 
X 
X 
 
X 
Cervicovaginal 
Sample 
Collection 
for 
STI 
Tests 
Trichomonas vaginalis (TV), Neisseria gonorrhoeae (NG) 
and Chlamydia trachomatis (CT) 
X 
 
 
 
X 
 
X 
Provision of treatment and/or referral for STIs and Other 
Findings 
 
 
 
 
 
X 
HIV Pre- & Post-Test Counselling 
X 
X 
X 
X 
X 
 


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Visits 
Screening 
Enrolment 
Trial Visits 
LPUV 
Exit Visit 
As needed 
Trial Months 
Screening 
must occur 
within 45 
days of 
enrolmentk 
0 
 Months 1-11h,i 
Month 12i 
Months 13-
14i 
HIV Rapid Tests b 
X 
X 
X 
X 
X 
X 
HIV-1 RNA PCR Test c, d 
X 
X 
X 
X 
X 
 
Plasma Viral Genotype Sample c, d 
X 
X 
X 
X 
X 
 
Plasma Dapivirine Concentrations 
 
 
X 
X 
 
 
Vaginal Fluid Dapivirine Concentrations 
 
 
X 
X 
 
 
Laboratory Testing for Safety Assessments e 
X 
 
 
 
 
X 
Urine Dipstick Analysis (Urine Microscopy If Clinically 
Indicated Only) 
X 
 
 
 
 
X 
RPR f 
X 
 
 
 
 
 
Cervical Sample Collection for Cytology g 
X 
 
 
 
 
X 
Final Laboratory results provided 
 
 
 
 
X 
 
 
a) 
Participant Questionnaire will be administered at all Trial Visits. 
b) 
Performed in accordance with HIV testing algorithm 
c) 
Sample will be stored and will only undergo testing subsequently or after confirmation of seroconversion and at every visit for seroconverters. 
d) 
Sample will be obtained at the point of two reactive HIV rapid tests and analysed subsequently or after confirmation of seroconversion. 
e) 
Blood draw by venepuncture for laboratory testing (haematology and chemistry). Haematology will include full blood counts, differential, and platelet count. Chemistry tests 
will include creatinine, AST and ALT. 
f) 
TPHA/TPPA should be performed if RPR positive. 
g) 
Cervical sample collection for cytology may be conducted at any study visit if no result is evident within the previous year, or abnormal at last cervical cytology. 
h) 
All women will attend a research centre follow-up visit one month after enrolment.  Following this visit, at investigator’s discretion, a participant can continue on a 3-monthly 
visit schedule.   Monthly visits may however be extended up to the first three months of participation. 
i) 
IPM will have the option to extend the trial period. 
j) 
Participants will receive a diary card at enrolment and at trial visits, as applicable.  Returned diary cards will be reviewed at all scheduled trial visits.  
k) 
Only procedures in italics required for participants rolling over directly from LPUV at IPM 027 to IPM 032. 
   


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APPENDIX B: HIV TESTING ALGORITHM 
 
Figure 1: Screening Algorithm 
 
 
 
 
Not eligible for 
enrolment; 
Refer for appropriate 
counselling and care 
TEST 1 
Non-reactive 
HIV-seronegative 
Discordant 
TEST 3 
Reactive 
HIV-seropositive 
 
Non-reactive 
HIV-seronegative 
 
Potentially eligible 
for enrolment 
Potentially eligible  
for enrolment 
TEST 2 
Reactive 
HIV-seropositive 


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Figure 2: Pre-Enrolment Algorithm 
 
 
Not eligible for 
enrolment; 
Refer for appropriate 
counselling and care 
TEST 1 
Non-reactive 
HIV-seronegative 
Discordant 
TEST 3 
Reactive 
HIV-seropositive 
 
Non-reactive 
HIV-seronegative 
Perform PCR Test 
If undetectable: 
Enrol; 
Sample for storage 
taken 
Enrol 
Sample for storage 
taken 
TEST 2 
Reactive 
HIV-seropositive 
If detectable: 
Not eligible for 
enrolment; 
Counsel as 
appropriate 


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Figure 3: Trial Visits Algorithm 
 
 
TEST 1 
Non-reactive 
HIV-seronegative 
Discordant 
TEST 3 
Reactive 
HIV-seropositive 
 
Non-reactive 
HIV-seronegative 
 
Undetectable HIV-1 RNA PCR result: 
Not infected; Continue IP  
 
HIV testing performed only at scheduled visits even 
if same pattern of discordant results continues 
Continue IP 
Sample for storage 
taken 
TEST 2 
Discontinue IP;  
Draw sample for 
endpoint confirmation 
by WB and other 
confirmatory tests; 
Analysis of stored 
samples 
Reactive 
HIV-seropositive 
Detectable HIV-1 RNA PCR result: 
 
HIV-infected; Discontinue IP 
Refer for appropriate counselling and care; 
Option to enrol in seroconverter protocol 
 
Continue IP and 
repeat testing in 2 
weeks 
At 2-week follow up visit: 
If same pattern of HIV rapid test results (discordant), 
collect a sample for quantitative HIV-1 RNA PCR 


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Figure 4: LPUV Algorithm 
 
 
 
 
TEST 1 
Non-reactive 
HIV-seronegative 
Discordant 
TEST 3 
Reactive 
HIV-seropositive 
 
Non-reactive 
HIV-seronegative 
 
HIV-negative 
Sample for storage 
taken 
TEST 2 
Reactive 
HIV-seropositive 
Draw sample for 
endpoint confirmation 
WB;  
Analysis of stored 
samples 
 
Refer for appropriate 
counselling and care; 
Option to enrol in 
seroconverter protocol 


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TEST 1 
Non-reactive 
HIV-seronegative 
Discordant 
TEST 3 
Reactive 
HIV-seropositive 
 
Non-reactive 
HIV-seronegative 
 
HIV-negative 
TEST 2 
Figure 5: Exit Visit Algorithm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Reactive 
HIV-seropositive 
Draw sample for 
endpoint confirmation 
WB; 
Analysis of stored 
samples 
 
Refer for appropriate 
counselling and care 


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APPENDIX C: VISIT SCHEDULE AND APPROXIMATE BLOOD VOLUMES 
 
Visit 
Test and 
volume 
(mL) 
Test and 
volume 
(mL) 
Test and 
volume 
(mL) 
Test and 
volume 
(mL) 
Test and 
volume 
(mL) 
Total 
Blood 
Volume 
Screening 
HIV rapid* 
5 mL 
 
Chemistry 
5 mL 
Haematology 
5 mL 
RPR 
5 mL 
HIV viral 
genotype 
resistance#  
10 mL 
HIV PCR# 
5 mL 
35mL 
 
 
 
 
 
 
 
Enrolment 
HIV rapid 
5 mL 
 
 
HIV viral 
genotype 
resistance#  
10 mL 
HIV PCR# 
5 mL 
20 mL 
 
 
 
 
 
 
 
Trial Visits 
HIV rapid 
5 mL 
Dapivirine 
levels# 
6 mL 
 
HIV viral 
genotype 
resistance#  
10 mL 
HIV PCR# 
5 mL 
26 mL 
 
 
 
 
 
 
 
LPUV 
HIV rapid 
5 mL 
Dapivirine 
levels# 
6 mL 
 
HIV viral 
genotype 
resistance#  
10 mL 
HIV PCR# 
5 mL 
26 mL 
 
 
 
 
 
 
 
Exit Visit 
HIV rapid^ 
5 mL 
 
 
HIV viral 
genotype 
resistance## 
10 mL 
HIV PCR# / 
## 
5 mL 
5 mL or 
15 mL## 
 
 
 
 
 
 
 
Seroconverter 
tests+ 
Western 
blot 
5mL 
Dapivirine 
levels++ 
6 mL 
 
HIV viral 
genotype 
resistance#  
10 mL 
HIV PCR# 
5 mL 
20 mL++ or 
26 mL 
 
• * Depending on the research centre SOP on HIV testing, sampling may be performed 
by finger prick or venepuncture.  
• # Stored plasma samples; tested retrospectively to evaluate different parameters at 
the time of seroconversion.  
• ## Blood samples for viral genotype resistance and HIV-1 RNA PCR testing will be 
collected at the scheduled exit visit following seroconversion.  
• ^ HIV rapid testing will not be conducted at the scheduled exit visit following 
seroconversion.  
• 
+ At the point of seroconversion, these samples will be collected and tested in addition 
to relevant visit-specific tests, but no samples should be duplicated during the same 
visit. No additional storage samples will be collected.  
NOTE: Additional tests may be also performed, as required.  
• 
++ Test sample for possible dapivirine measurements will not be required if the 
seroconversion occurs at the Exit Visit. 


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APPENDIX D: TRIAL DESIGN 
 
 
 
 
 
 
 
   
 
 
 
 
 
MONTH 12 
RING USE DISCONTINUED 
 
DAY 0 
RING INSERTION 
LPUV 
EXIT VISIT 
1-2 months 
≤ 45 days 
Monthly trial visit schedule 
 
First month after enrolment  
(or up to 3 months after enrolment at 
investigator’s discretion) 
3-monthly trial visit schedule 
2 additional rings dispensed at each trial visit, or 
dispensed as arranged 
ENROLMENT 
Approximately 
1400 women 
SCREENING 

SAP_003.pdf: 
 
IPM 032 
Statistical Analysis Plan 
 
CONFIDENTIAL 
CLIN-TEM-GEN-0001.00, 13Jan2016 
 
Page 1 of 1 
 
NCT02862171 
 
IPM 032 
 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF AND 
ADHERENCE TO THE DAPIVIRINE (25 mg) VAGINAL RING-004 IN HEALTHY, HIV-NEGATIVE 
WOMEN  
 
• 
Statistical Analysis Plan v1.0 dated 29 March 2019 
• 
SAP Appendix 13.1 – 13.7 
 
• 
Virology Addendum Analysis v1.0 dated 24 May 2021 
• 
Virology Addendum SAP, Appendix 1, Tables and Listings Shells, v1.0 dated  
24 May 2021 
 


IPM 032 
Statistical Analysis Plan, Draft, Version 1.0 
Version Dated: 29 Mar 2019 
 Page 1 of 39 
  
STATISTICAL ANALYSIS 
PLAN 
 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS 
CONTINUED SAFETY OF AND 
ADHERENCE TO THE DAPIVIRINE (25 mg) 
VAGINAL RING-004 IN HEALTHY, 
HIV-NEGATIVE WOMEN 
 
 
 
IPM 032  
(Based on: Protocol Version 2.0, Amendment 2.0, dated 16 January 2017) 
 
 
Version 1.0 
 
 
International Partnership for Microbicides 
8405 Colesville Road, Suite 600 
Silver Spring, MD 20910 USA 
 
 


IPM 032 
Statistical Analysis Plan, Draft, Version 1.0 
Version Dated: 29 Mar 2019 
 Page 2 of 39 
APPROVAL SIGNATURE PAGE 
IPM 032 – Statistical Analysis Plan 
 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF AND 
ADHERENCE TO THE DAPIVIRINE (25 mg) VAGINAL RING-004 IN HEALTHY, 
HIV-NEGATIVE WOMEN 
I have read the above referenced Statistical Analysis Plan and approve its contents. 
 
 
 
 
_________________________ 
 
Annaléne Nel, MBChB PhD  
 
Executive Vice President, Chief Medical Officer 
International Partnership for Microbicides 
 
 
 
 
_______________________ 
Date 
 
 
 
 
_________________________ 
 
Roland Klopper, MCom 
 
 
Statistics Manager 
Clindata Research Innovation 
 
 
 
 
_______________________ 
Date 
 
 
 
 
_________________________ 
 
Neliëtte van Niekerk, MCom  
 
Senior Director, Biometrics 
International Partnership for Microbicides 
 
 
 
 
_______________________ 
Date 
 
 
 


IPM 032 
Statistical Analysis Plan, Draft, Version 1.0 
Version Dated: 29 Mar 2019 
 Page 3 of 39 
Abbreviations 
AE 
 
 
 
Adverse Event 
ALT 
 
Alanine Aminotransferase 
AST 
 
 
 
Aspartate Aminotransferase  
ATC 
 
 
 
Anatomical Therapeutic Chemical 
BMI 
 
 
 
Body Mass Index 
CRF 
 
 
 
Case Report Form 
CSR 
 
 
 
Clinical Study Report 
DAIDS 
 
 
 
Division of Acquired Immunodeficiency Syndrome  
DSMB 
 
 
 
Data and Safety Monitoring Board 
EMA 
 
 
 
European Medicines Agency 
HIV 
  
 
 
Human Immunodeficiency Virus 
ICH 
 
 
 
International Conference on Harmonisation 
IP 
 
 
 
Investigational Product 
IPM 
 
 
 
International Partnership for Microbicides 
IRE 
 
 
 
Immediately Reportable Event   
ITT 
 
 
 
Intent-to-Treat 
MedDRA  
 
 
Medical Dictionary for Regulatory Activities  
m-ITT 
 
 
 
Modified Intent-to-Treat 
NRTI 
 
 
 
Nucleoside Reverse Transcriptase Inhibitor 
NNRTI 
 
 
 
Non-nucleoside Reverse Transcriptase Inhibitor 
PCR 
 
 
 
Polymerase Chain Reaction 
PI 
 
 
 
Protease Inhibitor 
PID 
 
 
 
Participant Identification Number 
PK 
 
 
 
Pharmacokinetic 
PP 
 
 
 
Per-Protocol 
PT 
 
 
 
Preferred Term 
QM&C 
 
 
 
Quality Management and Compliance 
RAM 
 
 
 
Resistance Associated Mutation 
RBC 
 
 
 
Red Blood Cells 
RNA 
 
 
 
Ribonucleic Acid 
RPR 
 
 
 
Rapid Plasma Reagin 
SAE 
 
 
 
Serious Adverse Event 


IPM 032 
Statistical Analysis Plan, Draft, Version 1.0 
Version Dated: 29 Mar 2019 
 Page 4 of 39 
SAP 
 
 
 
Statistical Analysis Plan 
SD 
 
 
 
Standard Deviation 
SOC 
 
 
 
System Organ Class 
STI 
 
 
 
Sexually Transmitted Infection 
TEAE 
 
 
 
Treatment Emergent Adverse Event 
TPHA 
 
 
 
Treponema Pallidum Haemagglutination Test 
TPPA 
 
 
 
Treponema Pallidum Particle Agglutination Assay 
WBC 
 
 
 
White Blood Cells 
WHO DDE 
 
 
World Health Organization Drug Dictionary Enhanced 


IPM 032 
Statistical Analysis Plan, Draft, Version 1.0 
Version Dated: 29 Mar 2019 
 Page 5 of 39 
Table of Contents 
1. 
INTRODUCTION ................................................................................................................ 8 
2. 
TRIAL OBJECTIVES .......................................................................................................... 9 
2.1 
Primary Objectives ....................................................................................................... 9 
2.2 
Secondary Objectives .................................................................................................. 9 
2.3 
Exploratory Objectives ................................................................................................. 9 
2.4 
Assessment of Objectives ............................................................................................ 9 
3 
TRIAL DESIGN ..................................................................................................................11 
3.1 
General Design and Plan ............................................................................................11 
3.2 
Sample Size................................................................................................................12 
3.3 
Randomisation ............................................................................................................12 
3.4 
Blinding .......................................................................................................................12 
4 
SEQUENCE OF PLANNED ANALYSES............................................................................12 
4.1 
Safety Monitoring ........................................................................................................12 
4.2 
Interim Analyses .........................................................................................................12 
4.3 
Final Analysis and Reporting ......................................................................................13 
5 
ANALYSIS POPULATIONS ...............................................................................................13 
5.1 
Safety Population ........................................................................................................13 
5.2 
Modified Intent-to-Treat (m-ITT) Population ................................................................13 
5.3 
Virology Population .....................................................................................................13 
5.4 
Per-Protocol (PP) Population ......................................................................................13 
6 
GENERAL STATISTICAL CONSIDERATIONS..................................................................14 
6.1 
Analysis Software .......................................................................................................14 
6.2 
Methods for Handling Missing Data ............................................................................14 
6.3 
Multiple Comparisons and Multiplicity .........................................................................14 
6.4 
Multicentre Trials ........................................................................................................14 
6.5 
Planned Subgroups, Interactions, and Covariates ......................................................14 
6.6 
Data Presentations .....................................................................................................15 
7 
TRIAL PARTICIPANTS ......................................................................................................16 
7.1 
Disposition of Trial Participants ...................................................................................16 


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7.2 
Protocol Deviations .....................................................................................................17 
7.3 
Adherence to Ring Regimen .......................................................................................18 
7.3.1 
Dapivirine Ring Residual Levels in Used Rings ....................................................18 
7.3.2 
Self-reported Adherence ......................................................................................18 
8 
EVALUATION OF DEMOGRAPHIC AND BASELINE CHARACTERISTICS ......................18 
8.1 
Baseline Demographics ..............................................................................................19 
8.2 
Baseline Medical History .............................................................................................19 
8.3 
Baseline Screening Assessments ...............................................................................19 
8.4 
Prior Therapies and Medications .................................................................................20 
9 
EVALUATION OF TRIAL ENDPOINTS ..............................................................................20 
9.1 
Primary Endpoint 1 – Safety .......................................................................................20 
9.2 
Primary Endpoint 2 – Adherence ................................................................................20 
9.3 
Secondary Endpoints ..................................................................................................22 
9.3.1 
Secondary Endpoint 1: HIV-1 seroconversion rate per 100 person-years of product 
use 
22 
9.3.2 
Secondary Endpoint 2: HIV-1 drug resistance mutations among participants who 
acquire HIV-1 .....................................................................................................................24 
9.4 
Exploratory Endpoints .................................................................................................26 
9.4.1 
Exploratory Endpoint 1: Participant report of feasibility of 3-monthly clinical follow-
up schedule .......................................................................................................................26 
9.4.2 
Exploratory Endpoint 2: Correlation between dapivirine residual amounts in 
returned used vaginal rings and/or drug concentrations, and results from visual inspection 
of returned vaginal rings .....................................................................................................27 
9.4.3 
Exploratory Endpoint 3: Proportion of participants opting for HIV rapid tests at the 
research centre between scheduled 3-monthly visits .........................................................28 
9.4.4 
Exploratory Endpoint 4: Self-reported acceptability and adherence to vaginal ring 
use 
28 
10 EVALUATION OF SAFETY PARAMETERS ......................................................................29 
10.1 
Adverse Events .......................................................................................................29 
10.1.1 
Treatment Emergent Adverse Events (TEAEs) ....................................................30 
 
TEAEs are defined as AEs which occurred/worsened after the first insertion of the 
IP, up to  six weeks after last ring use. Only TEAEs are reported in the AE CRF. ..............30 


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10.1.2 
Product-related Adverse Events...........................................................................30 
10.2 
Clinical Laboratory Evaluation .................................................................................33 
10.3 
Pelvic examinations .................................................................................................34 
10.3.1 
Assessments .......................................................................................................34 
10.3.2 
Summary Tables ..................................................................................................34 
10.4 
Cervical cytology .....................................................................................................35 
10.4.1 
Assessments .......................................................................................................35 
10.4.2 
Summary Tables ..................................................................................................35 
10.5 
STI assessments .....................................................................................................35 
10.5.1 
Assessments .......................................................................................................35 
10.5.2 
Summary Tables ..................................................................................................35 
10.6 
Immediately Reportable Events ...............................................................................36 
10.6.1 
Assessments .......................................................................................................36 
10.6.2 
Summary Tables ..................................................................................................36 
10.7 
Concomitant Medications ........................................................................................37 
10.8 
Physical Examination Findings and Vital Signs........................................................38 
10.9 
Social Harms ...........................................................................................................38 
11 CHANGES IN THE PROTOCOL-PLANNED ANALYSES ..................................................39 
12 REFERENCES ..................................................................................................................39 
13 APPENDICES ....................................................................................................................39 
13.1 
Appendix 1 – Table Shells .......................................................................................39 
13.2 
Appendix 2 – Figure Shells ......................................................................................39 
13.3 
Appendix 3 – Individual Participant Listing Shells ....................................................39 
13.4 
Appendix 4 –  Stanfort HIV-1 Drug Resistance (database version 8.4 – dated 2017-
06-16) 
39 
13.5 
Protocol deviation criteria ........................................................................................39 
 
 
 


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Statistical Analysis Plan, Draft, Version 1.0 
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1. INTRODUCTION 
This document serves as the Statistical Analysis Plan (SAP) for the protocol pre-specified 
primary, secondary and exploratory endpoints for IPM 032, the Phase IIIb follow-on trial 
to IPM 027. Specifically, this document describes the statistical methods that will be used 
to analyse the final data from IPM 032 to support the completion of the Clinical Study 
Report (CSR). The planned analyses described in this SAP will form the basis for the 
assessment of safety and adherence to the use of the Dapivirine Vaginal Ring-004, as 
determined in the follow-on trial, and will be included in regulatory submissions and/or 
future manuscripts. Also, exploratory analyses not necessarily identified in this SAP may 
be performed. 
Table shells, example figures, and listing shells that will accompany the analysis are 
provided in Appendices 1, 2, and 3, respectively. The appendices are viewed as 
supporting material of the analysis and will not require signature approval if formatting 
changes are made.  
This document is based on the current version of the IPM 032 trial protocol, Version 2.0, 
Amendment 2.0, which was approved on 16 January 2017. However, due to changes in 
the global donor environment, not all planned changes from protocol Version 2.0, 
Amendment 1.0 (dated 22 October 2015) were implemented. The sections in protocol 
Version 2.0, Amendment 2.0 that have been implemented are detailed in Appendix 6.  
This analysis plan refers to Case Report Forms (CRFs) Version 1.0, dated 16 May 2016, 
and additional CRFs for capturing screen failure information (Version 2.0, dated 23 May 
2016). The following CRFs were updated during the trial:  
• 
Contraceptive/menstrual/obstetric history (CMO) CRF, end of trial inventory (ETI) 
CRF, menses information and pregnancy test results (PTR) CRF, pregnancy 
outcome 1 (PO1) CRF, ring insertion/removal (RL) log CRF, and HIV 
seroconversion evaluation (SERCON) CRF (Version 1.0, dated 16 May 2016, and 
Version 2.0, dated 27 April 2017 used starting 16 October 2017). 
The following CRFs were developed during the course of the trial and implemented as 
indicated: 
• 
Narrative log (NARR) CRF, returned ring log (RRL) CRF, seroconversion – HIV 
RNA PCR testing (SER PCR) CRF, and screening and enrollment (SEL) log CRF 
(Version 1.0, dated 27 April 2017 implemented starting 16 October 2017); 
participant transfer (PTRAN) CRF (Version 1.0, dated 28 June 2017, implemented 


IPM 032 
Statistical Analysis Plan, Draft, Version 1.0 
Version Dated: 29 Mar 2019 
 Page 9 of 39 
starting 20 July 2017); and participant receipt (PREC) CRF (Version 1.0, dated 28 
June 2017, implemented starting 15 August 2017).  
2. TRIAL OBJECTIVES 
2.1 Primary Objectives 
The primary trial objectives are: 
• 
To assess the safety profile of the 25 mg Dapivirine Vaginal Ring-004, when 
inserted at monthly intervals, in an open-label trial. 
• 
To assess adherence to the use of the 25 mg Dapivirine Vaginal Ring-004 inserted 
at monthly intervals, in an open-label trial. 
2.2 Secondary Objectives 
The secondary trial objectives are: 
• 
To assess the incidence of HIV-1 seroconversion. 
• 
To assess the frequency of HIV-1 drug resistance in women who acquire HIV-1 
infection. 
2.3 Exploratory Objectives 
The exploratory trial objectives are: 
• 
To assess the feasibility of 3-monthly follow-up visits, as a possible schedule for 
post-licensure vaginal ring clinical follow-up. 
• 
To explore the correlation between drug concentrations and results from the visual 
inspection of the returned vaginal rings by research staff between the monthly and 
3-monthly research centre follow-up schedules. 
• 
To determine the proportion of participants electing to undergo HIV rapid tests at 
the research centres between scheduled 3-monthly visits. 
• 
To characterize the IPM 027 participants who decline enrollment into IPM 032 
(Decliner Population) [Not implemented.] 
• 
To explore self-reported acceptability of and adherence to the 25 mg Dapivirine 
Vaginal Ring-004. 
 
Note: Objectives indicated as “Not implemented” above, are not addressed in this 
analysis plan. 
2.4 Assessment of Objectives 
Consistent with the primary objectives, the primary endpoints are: 
Safety 
• 
All Adverse Events (AEs) assessed by the investigator to be related to the 
Dapivirine Vaginal Ring-004. 


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• 
All Grade 3 and 4 AEs. 
• 
All Serious Adverse Events (SAEs). 
Adherence 
Residual amounts of dapivirine in returned rings and/or dapivirine concentrations in 
plasma and/or dapivirine concentrations in vaginal fluid. 
The primary endpoints will be assessed through: 
Safety 
All product-related AEs, Grade 3 or 4 AEs, SAEs, physical examination, 
gynaecological assessments, including pelvic/speculum examination, laboratory tests 
and other indicated investigations. 
Adherence 
• 
Determined dapivirine residual amounts in returned used vaginal rings and/or 
• 
Measured concentrations of dapivirine in plasma [Not implemented] and/or  
• 
Measured concentrations of dapivirine in vaginal fluids [Not implemented.] 
Consistent with the secondary objectives, the secondary endpoints are: 
• 
The HIV-1 seroconversion rate per 100 woman-years of product use at the end of 
the vaginal ring use period. 
• 
HIV-1 drug resistance mutations among participants who acquire HIV-1 infection. 
The secondary endpoints will be assessed through: 
• 
Rapid and specialised laboratory testing according to a pre-specified HIV testing 
algorithm. 
• 
Viral genotype resistance testing methods which include sensitive methods to 
detect low frequency drug-resistant variants (only population genotyping will be 
done.) 
Consistent with the exploratory objectives, the exploratory endpoints include: 
• 
Feasibility of a 3-monthly clinical follow-up schedule. 
• 
Dapivirine residual amounts in returned used vaginal rings and/or dapivirine 
concentrations in plasma and/or vaginal fluid in correlation with results from the 
visual inspection of the returned used vaginal rings by research staff. 
• 
Proportion of participants opting for HIV rapid tests at the research centre between 
scheduled 3-monthly research centre follow-up visits. 
• 
The proportion of women who report the use of the vaginal ring as acceptable. 
• 
Participant self-reported patterns of ring use. 
The exploratory endpoints will be assessed through:  


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• 
Participant report of feasibility regarding a 3-monthly clinical follow-up schedule 
(Participant Questionnaire). 
• 
Number of women opting not to receive two additional rings at the 3-monthly visits. 
• 
Proportion of returned rings (used and unused) during the 3-monthly clinical follow-
up schedule. 
• 
Dapivirine residual amounts in returned used vaginal rings and/or dapivirine 
concentrations in blood and/or vaginal fluid. 
• 
Visual inspection of the returned used vaginal rings by research centre staff. 
• 
Number of participants undergoing HIV rapid tests at the research centre between 
scheduled 3-monthly research centre follow-up visits. 
• 
Qualitative data regarding ring acceptability and self-reported patterns of ring use. 
 
Note: Although collected and stored, blood and vaginal fluid samples were not 
analysed for dapivirine, as dapivirine concentrations were found in the Phase III 
program to have limited value as adherence measures. There is currently no 
biomarker to indicate whether the ring was used at the time of an HIV risk event; the 
best measure of ring use during the prescribed 1-month use period is dapivirine ring 
residual levels in used rings. 
3 TRIAL DESIGN 
3.1 General Design and Plan 
IPM 032 is a Phase IIIb, multi-centre follow-on open-label trial to evaluate the 
continued adherence to and safety of the Dapivirine Vaginal Ring-004 inserted at 
monthly intervals in healthy, HIV-negative women who have participated in the  
IPM 027 Phase III Dapivirine Vaginal Ring-004 trial. All women who have participated 
in IPM 027 and are HIV-negative at screening for IPM 032, will be eligible. It was 
estimated that approximately 1400 participants will be enrolled. 
All participants will attend a research centre follow-up visit one month after enrollment. 
Following this visit, at the investigator’s discretion, a participant can continue on a 3-
monthly visit schedule. Monthly visits may however be extended up to the first three 
months of participation. Once the 3-monthly trial visit schedule commences, three 
rings will be dispensed to the participant. One ring will be self-inserted at the research 
centre and two additional rings will be dispensed for the participant to take home, or 
dispensing will take place as arranged with the participant. 
Each participant will engage in the screening process for up to 45 days prior to 
enrollment and will use the Dapivirine Vaginal Ring-004 for a period of up to 12 months. 
IPM will have the option to extend this trial period. Accrual was expected to take place 
over approximately 6 months; participants enrolled more than 6 months after the onset 
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Each participant will have an exit visit 1 to 2 months after ring discontinuation, to 
assess safety and identify HIV-1 seroconversions after product discontinuation.  
 
3.2 Sample Size 
This is an open-label, follow-on trial to IPM 027 to evaluate the safety of and adherence 
to the Dapivirine Vaginal Ring-004, inserted at monthly intervals in healthy, HIV-
negative women who have participated in the IPM 027 trial. No formal sample size or 
power calculations have thus been performed. It was expected that approximately 
70% of the participants enrolled in IPM 027 will participate in this trial. Therefore, a 
total sample size of approximately 1400 HIV-negative women was anticipated. 
3.3 Randomisation 
This is an open-label, follow-on trial. No randomisation will be done. 
3.4 Blinding 
This is an open-label study. No blinding will be performed. 
4 SEQUENCE OF PLANNED ANALYSES 
4.1 Safety Monitoring  
Safety data from the trial were to be evaluated by an independent Data and Safety 
Monitoring Board (DSMB). The first scheduled meeting was to take place 
approximately six months after all research centres had been activated; subsequent 
meetings were held at approximately annual intervals for the duration of IPM 032. 
Based on the review of the data, the DSMB was required to provide recommendations 
about continuation, pausing, termination or other modifications to the trial, including 
changes to the information provided to participants for obtaining their informed 
consent. An IPM 032 DSMB charter was developed to describe the roles and 
responsibilities of the DSMB, its composition, data to be provided to the DSMB, the 
process for disseminating trial data to the DSMB, and the communication plan 
between the DSMB and IPM. 
4.2 Interim Analyses 
No interim analysis was planned for this trial. However, the Sponsor reviewed the 
treatment emergent safety data at regular intervals during the conduct of the trial. 
Note: Although no formal interim analysis was planned or conducted for IPM 032, two 
summary reports of available data as of 30 April 2018 and 08 November 2018, 
respectively, were prepared and submitted to the European Medicines Agency (EMA), 
in response to requests by EMA during their review of the Dapivirine Vaginal Ring 
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4.3 Final Analysis and Reporting 
This SAP will be approved before final database lock. All final and planned analyses 
identified in the protocol and in this SAP will be performed only after the database has 
been locked. A review of the data will be performed prior to database lock for data 
quality purposes and for classification of protocol deviations as minor or major. 
5 ANALYSIS POPULATIONS 
Four analysis populations have been defined for this trial: a Safety population, Modified 
Intent-to-treat (m-ITT) population, Virology population and a Per-protocol (PP) or 
Protocol-adherent population. The number of participants valid for each population, 
and when appropriate, the reasons for excluding trial participants from these 
populations, will be presented overall and by research centre using relevant summary 
statistics. 
5.1 Safety Population 
The safety population will include all participants who were enrolled, and received and 
inserted at least one Dapivirine Vaginal Ring 
5.2 Modified Intent-to-Treat (m-ITT) Population 
Some participants recently infected with HIV-1 may not yet have detectable levels of 
HIV-1 antibodies at the enrollment visit, and therefore, HIV-infected women who are 
assumed to be HIV-negative may be enrolled in the trial. To accommodate this 
situation, an m-ITT population will be determined and used for the analysis of HIV-1 
seroconversion rate. This population will exclude all participants who are included in 
the safety population but who were found to have been HIV-1 infected at the 
enrollment visit (i.e. women who have seroconverted after enrollment but were 
retrospectively found to be HIV-1 RNA positive at enrollment).  
Virology Population 
The virology population includes all participants in the m-ITT population, with the 
exception of those participants who seroconverted after the last product use visit 
(LPUV). That is, women who were still HIV-1 RNA negative at LPUV, and who became 
infected after discontinuation of ring use, will be excluded. Genotypic analyses from 
the small numbers of participants with infection at enrolment, or with no detectable 
HIV-1 RNA at the LPUV but with seroconversion at the Exit visit, will be described 
separately. 
5.3 Per-Protocol (PP) Population 
The PP (or protocol-adherent) population is a subset of the m-ITT population, i.e. all 
trial participants who are confirmed as HIV-1 negative at the enrollment visit, with no 
major protocol deviations, as defined in Section 7.2. 


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6 GENERAL STATISTICAL CONSIDERATIONS 
6.1 Analysis Software 
Statistical analyses will be conducted by an external statistical service provider 
(Clindata Research Innovation) and reviewed by the International Partnership for 
Microbicides (IPM). The analyses will be performed using SAS® for Windows (version 
9.3 or higher, SAS Institute Inc., Cary, North Carolina, USA).  
6.2 Methods for Handling Missing Data 
While every effort will be made to minimise the amount of missing data, some degree 
of missing data, primarily associated with missed visits, is expected. The amount of 
missing data will be explored and incorporated into the analyses, where appropriate. 
For the analysis of adherence to monthly ring use, patterns of missing data may be 
informative. Depending on the proportion of participants who discontinue early, an 
analysis of time to discontinuation may be conducted. Such an analysis would allow 
investigation of the covariates associated with early discontinuation. Patterns of 
missing data may also provide further insight into participants’ preference for monthly 
or 3-monthly follow-up visits to research centres. 
6.3 Multiple Comparisons and Multiplicity 
The primary safety analysis is a descriptive analysis of the proportion of participants 
experiencing AEs. The primary adherence analysis is also descriptive in nature. As a 
result, no adjustments are required for multiplicity.  
6.4 Multicentre Trials 
Differences in participant safety and adherence to the dapivirine vaginal ring across 
research centres will be explored graphically and descriptively. The safety and 
adherence analyses will be summarised overall and for each research centre 
separately.   
6.5 Planned Subgroups, Interactions, and Covariates 
The analysis of the HIV-1 seroconversion rate will be based on the m-ITT population, 
and the primary virology analysis of drug resistance will be based on the virology 
population. It is expected that women with pre-existing conditions (e.g. women with 
STIs at Screening) will be treated and evaluated before or at enrolment into the trial, 
therefore no baseline adjustments are planned prospectively; however, all data will be 
reviewed to assess any potentially relevant baseline imbalances between research 
centres.  
Unless specified otherwise, statistical models will include research centre as main 
effect. Kaplan-Meier survival curves will be produced overall and by research centre, 
if possible. 
The following subgroup analysis will be performed for the primary safety endpoint (AEs 
related to Investigational Product (IP), Grade 3 and 4 AEs and SAEs):  


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1. Participants in the age group < 25 years, and ≥ 25 years 
The following subgroup analysis will be performed for the primary adherence endpoint 
(residual amounts of dapivirine in returned rings): 
1. Participant age at baseline (< 25 versus ≥ 25 years) 
2. Marital status at baseline (married versus not married) 
3. Has a main sex partner at baseline (yes versus no) 
4. Presence of genital symptoms/Sexually Transmitted Infections (STIs) at baseline 
(yes versus no) 
6.6 Data Presentations 
Descriptive statistics will be presented overall and by research centre.  
For continuous variables, the descriptive statistics will include, but not be limited to, 
mean and standard deviation (SD) (when appropriate), quartiles, range, and number 
of observations. For categorical variables, descriptive statistics may include 
frequencies, relative frequencies, and the number of observations. 
Derived data where it is known in advance the result will be an integer (e.g. study day) 
will be presented with no decimal places. Means, medians and quartiles will be 
displayed to one more decimal place than the source data, dispersion statistics (e.g. 
standard deviation) will have two more decimal places, and the minimum and 
maximum will be displayed to the same number of decimal places as reported in the 
raw data. Percentages will be presented to one decimal place (excluding 0 and 100%). 
When appropriate, 95% confidence intervals will be presented.  
The subsequent sections discuss the planned analyses beyond the listings and simple 
descriptive analyses.  
Baseline is defined as the last available measurement before the first insertion of the 
IP. All visit dates will be calculated from the enrollment visit as baseline date. 
Missing or partial dates will be imputed for AEs or concomitant medication dates. No 
other date imputations will be performed. For AEs or concomitant medication start 
dates, the following conventions will be applied: 
2. If only the month and year are known, then the 15th of the month will be used (i.e. 
“15” will be imputed as the day of the month) unless the month and the year equal 
the month and the year of the first insertion of the ring. In such cases, the same 
day as the day of first ring insertion will be used (to ensure that the AE or 
concomitant medication is considered as treatment-emergent) 
3. If only the year is known, then the first day of January will be used (i.e. “01JAN” 
will be imputed as the day and month) unless the year equals the year of first ring 
insertion, in which case the date will be imputed with the date of first ring insertion. 
For concomitant medication end dates, the following conventions will be applied: 


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4. If only the month and the year are known, then the last day of the month will be 
used 
5. If only the year is known, then the last day of December (i.e. “31DEC”) or the date 
of trial completion/discontinuation will be used (whichever comes first). 
In instances where the date of IP initiation, i.e. the start date of ring use, is missing or 
unknown, the missing date will be imputed with the date of the enrollment visit. 
In accordance with the protocol, each scheduled visit has a window period of ± 7 days. 
If the participant does not return to the research centre for a scheduled visit prior to 
the start of the trial window of the next visit, the visit will be considered missed. If a 
participant presents for a visit outside the window for a scheduled trial visit, but prior 
to the start of the window for the next visit, it will be treated as a late visit. Missed visits 
and late visits will be documented as protocol deviations (refer to Section 7.2). Data 
recorded at late visits will be analysed as pertaining to the scheduled visit. 
Unscheduled visits may be performed at any time during the trial. If an unscheduled 
visit takes place within any given window period and any repeat observations are made 
within the given window period, the repeat values will be captured as pertaining to the 
unscheduled visit. Data from scheduled and unscheduled visits will be shown in the 
participant listings, and listings will be appropriately labelled when data arise from 
unscheduled visits. Data from scheduled visits will be presented in the summary 
tables.  
Visit Schedule A will consist of participants who attend Trial Month Visits 1, 4, 7, 10, 
13, and 16/Exit; Visit Schedule B will consist of participants who attend Trial Month 
Visits 1, 2, 5, 8, 11, 14, and 17/Exit; and Visit Schedule C will consist of participants 
who attend Trial Month Visits 1, 2, 3, 6, 9, 12, and 15/Exit. 
Tables, figures, and listings of trial results will accompany the text of the CSR. Listings 
of all clinical data recorded in the CRFs will be provided, except for those CRFs which 
are used for administrative purposes, such as the Participant Encounter Form (PEN) 
and the End of Trial Inventory (ETI). Listings will be sorted by research centre and 
participant identification number (PID), and key variables such as visit date and/or trial 
visit number will be presented in each listing. 
7 TRIAL PARTICIPANTS 
All participants who provide informed consent for this trial will be accounted for, in 
accordance with ICH guideline E3 (Structure and Content of Clinical Study Reports)2. 
7.1 
Disposition of Trial Participants 
The number and percentage of trial participants who were screened, enrolled, 
received IP, permanently discontinued IP, permanently discontinued the trial, and who 
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For those participants who were prematurely discontinued from the trial, the time to 
permanent discontinuation of IP and the time to permanent discontinuation from the 
trial will be calculated, and presented together with Kaplan-Meier curves overall and, 
if appropriate, by research centre, and baseline covariates where appropriate (refer to 
Section 6.5; subgroups 1 to 4). Two separate probability curves will be presented;  
• 
All reasons for premature discontinuation combined; and 
• 
All reasons for premature discontinuation excluding seroconversion.  
For participants that do not discontinue prematurely, the time to event duration will be 
censored as follows: 
• 
For time to premature discontinuation of IP, the event date will be censored at 
the date of last known IP use 
• 
For time to premature discontinuation from the trial, the event date will be 
censored at the date of last contact 
For all participants the time to discontinuation from the trial (scheduled or premature) 
will be calculated and presented together with Kaplan-Meier curves overall and if 
appropriate by research centre, and baseline covariates where appropriate.  
The time to an event will be calculated as follows: 
• 
Time 
to 
event 
(days) 
= 
(Date 
of 
IP 
discontinuation/trial 
discontinuation/Censoring Date – Date of first ring use) + 1 
A listing reflecting each participant’s screening date, enrollment date, and scheduled 
and unscheduled visit dates, as documented in the PEN CRF, will be provided.  
7.2 
Protocol Deviations  
All recorded protocol deviations will be listed and summarised overall and by research 
centre. 
The IPM Clinical Trial Physician(s) (one or more IPM physicians assigned to 
continually monitor trial data during the course of the trial) will establish protocol 
deviation criteria for the trial, in conjunction with the IPM Head of Quality Management 
and Compliance (QM&C), the Head of Biometrics and other clinical team members, 
as appropriate. The final list of protocol deviation criteria will be approved by the IPM 
Chief Medical Officer. Before database lock and statistical analysis, all reported 
protocol deviations will be reviewed by the IPM Clinical Trial Physician(s), Head of 
QM&C and Head of Biometrics, in conjunction with the trial statistician (from Clindata 
Research Innovation), to determine the impact of each deviation on the analysis, and 
to compile a final list of major protocol deviations for purposes of defining the PP 
analysis population. The final list will be signed off by the IPM Chief Medical Officer.  
Major protocol deviations that will result in exclusion of a participant from the PP 
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• 
Inappropriate enrollment into the trial (e.g. participant met an exclusion 
criterion, or participant failed to meet all inclusion criteria) as documented in 
the Deviations Log (DL) CRF. A major deviation will exclude the participant 
completely from the population. 
• 
IP-related deviations (e.g. IP was incorrectly withheld from participants, 
participants incorrectly resumed IP use, or inappropriate IP was dispensed to 
a participant). The data of such participants will be censored at the date of the 
last negative HIV-1 test result prior to the occurrence of the deviation. 
• 
The participant demonstrated non-adherence to IP use, evident from any 
missed 3-monthly research centre visits. The data of such participants will be 
censored at the date of the last negative HIV-1 test result prior to the first 
missed 3-monthly visit.    
• 
Any other major protocol deviation identified during review of the data that may 
impact the integrity of the data. The decision whether the participant should be 
excluded entirely from the population or whether the data of the participant 
should be censored will be made during the review of the protocol deviations. 
The number of participants with minor and major protocol deviations will be presented 
using appropriate summary statistics, overall and by research centre.   
7.3 
Adherence to Ring Regimen 
The data collected in IPM 032 allows for both objective and subjective assessments 
of adherence to ring use by the participants in this trial.  
Dapivirine residual levels in returned used rings are used as objective, quantitative 
measure of adherence to ring use in this trial. 
Subjective adherence measures include self-reported ring use as collected on the 
Accidental Expulsion/Removal Log (EXP) CRF. Missed clinical trial visits are also used 
as an indicator of non-adherence to prescribed product use.  
7.3.1 
Dapivirine Ring Residual Levels in Used Rings 
A comprehensive description of the planned analysis of dapivirine ring residual levels 
is provided in Section 9.2. 
7.3.2 
Self-reported Adherence 
A comprehensive description of the planned analysis of self-reported adherence to the 
ring regimen is provided in Section 9.4.4. 
8 EVALUATION OF DEMOGRAPHIC AND BASELINE CHARACTERISTICS 
Unless otherwise specified, baseline characteristics, including medical history (MED), 
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at the Screening and Enrollment visits, will be summarised descriptively, overall and by 
research centre, using appropriate summary statistics as described in Section 6.6.  
8.1 
Baseline Demographics  
The following baseline demographic characteristics will be listed and summarised:  
age, race, height, weight and body mass index (BMI), education level, relationship 
status, current residential status with main sex partner, information on vaginal sex 
once a week or more, usual number of vaginal sex acts, genital STIs at baseline, 
number of male sex partners at baseline, partner knowledge of ring use and whether 
the participant has children or not. Age and BMI will be derived as described in Table 
1 below. 
Table 1 Derived and Computed Demographic Variables 
Variable 
Name 
Description 
Computation Methods, Notes, or 
Equation(s) 
Age 
Age (years) 
INT((date of enrollment – date of birth)/365.25) 
BMI 
Body Mass Index (kg/m2) 
(Participant body weight in kg)/  
(Participant height in m)2 
Qualitative demographic characteristics (nominal or ordinal categories) will be 
summarised using absolute and relative frequencies. Quantitative demographic 
characteristics (continuous) will be summarised using the appropriate summary 
statistics, namely number of participants, mean, SD, quartiles, and range.  
The demographic characteristics will be summarised by research centre, IPM 027 
treatment arm, seroconversion status and overall. An additional table will be created 
to summarise the demographic characteristics by research centre, overall and IPM 
032 enrollment status (IPM 027 participants enrolled into IPM 032 vs not enrolled in 
IPM 032).  
All demographic and baseline characteristics will be presented in participant listings.   
8.2 
Baseline Medical History 
Medical history will be collected during the Screening visit and Trial Visit 0 (pre-
enrollment). Medical history will be presented in tabular form using appropriate 
descriptive statistics. All medical history will be listed. 
8.3 
Baseline Screening Assessments 
Laboratory assessments conducted at baseline, including cytology, syphilis testing 
(Rapid Plasma Reagin [RPR]; confirmatory Treponema Pallidum Haemagglutination 
Test/Treponema Pallidum Particle Agglutination Assay [TPHA/TPPA]), haematology, 
biochemistry, urinalysis, urine pregnancy tests, and HIV rapid tests will be presented 
for all participants. General physical examination and pelvic examination results will 
be presented at the Screening visit for all participants.   


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Obstetrics and gynaecological history will be collected during the Screening visit, and 
gynaecological conditions will be coded using Version 19.0 of the Medical Dictionary 
for Regulatory Activities (MedDRA). Obstetrics and gynaecological history will be 
presented in tabular form with absolute and relative frequencies, and gynaecological 
conditions will be classified using System Organ Class (SOC) and Preferred Term 
(PT).   
8.4 
Prior Therapies and Medications 
Prior medication is defined as any medication that started and ended before the first 
insertion of IP. Medications will be coded using the World Health Organization Drug 
Dictionary Enhanced (WHO DDE) (version June 2017). A table summarising the 
number and percentage of participants using drugs, by Anatomical Therapeutic 
Chemical (ATC) level 2 classification and preferred name, will be presented.  
9 EVALUATION OF TRIAL ENDPOINTS 
9.1 
Primary Endpoint 1 – Safety 
The analysis of AEs will be mainly descriptive in nature. That is, the number and 
percentage of participants experiencing AEs will be presented per SOC and PT, 
overall and by research centre. The proportion of participants experiencing the 
following will be determined and summarized: 
• 
AEs considered by the Investigator as related to IP 
• 
Grade 3 or 4 AEs 
• 
SAEs 
For these three endpoints, and for the most frequently reported AEs (i.e. AEs occurring 
in at least 5% of participants overall) the proportion and the corresponding 95% 
confidence interval will be presented for the overall counts. The confidence interval 
will be determined using Fisher’s exact test.  
Separate tabulations will be created for AEs of special interest (selected urogenital 
AEs and STIs). For this purpose, PTs may be grouped into categories of interest (refer 
to Appendix 5). 
9.2 
Primary Endpoint 2 – Adherence 
Dapivirine residual levels in used rings will be determined for all participants receiving 
IP, as a measure of adherence to ring use. The data will be listed, summarised and 
presented graphically, as described below. 
Dapivirine Residual Levels in Used Rings 
All used vaginal rings that are returned to the research centres at each trial visit are 
collected and shipped at regular, pre-defined intervals to an analytical laboratory, 


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where the rings are analysed to determine the residual amounts of dapivirine in the 
rings. 
For this trial, a reported ring residual level of > 23.5 mg dapivirine will be used as an 
indication of non-adherence to ring use over the 30-day period (± 7 days) that a woman 
was to keep the ring in situ. Based on the data from the Phase III program, the cut-off 
value of > 23.5 mg for dapivirine ring residual levels was shown to be a good measure 
of non-adherence to ring use, indicating no or very little ring use. 
The following summaries and graphical presentations will be produced for these data: 
• 
A summary of ring residual levels at each trial visit and at the time of 
seroconversion, the time of first HIV-1 RNA positive as well as the time of last 
HIV-1 RNA negative will be presented with standard descriptive statistics – 
presented overall, by IPM 027 treatment arm, and by research centre. 
Corresponding box plots will be prepared. 
• 
A descriptive summary of the ring residual levels by trial visit and by category 
of residual amount (< 20 mg, 20 – 21 mg, > 21 – 22 mg, > 22 – 23.5 mg, and 
> 23.5 mg). This summary will be prepared overall, by IPM 027 treatment arm 
and by research centre, with corresponding bar charts. 
• 
A summary relating the ring residual levels to time intervals (in days) between 
consecutive ring replacements (< 23 days, 23 – 37 days, > 37 – 84 days, and 
> 84 days). Corresponding box plots will be prepared. 
 
Note: All summaries and graphical presentations will be produced for both 
uncorrected dapivirine ring residual levels (as reported by the analytical laboratory) 
and residual levels corrected for manufacturing and assay variability, unless 
otherwise specified.  
The aforementioned graphical presentations will be repeated for the ring residuals 
from the IPM 027 and IPM 032 trials, and will be based only on the participants from 
IPM 027 who enrolled in IPM 032. However, only the uncorrected ring residual levels 
will be used. 
In addition, a listing will be produced for those trial participants who HIV-1 
seroconverted, with HIV-1 infection estimated to have occurred on IP, listing the date 
of the last negative HIV RNA PCR test, the date of the first positive HIV RNA PCR 
test, the number of days in-between, the time to first positive HIV-1 RNA, the 
corresponding corrected and uncorrected dapivirine ring residual levels, and the 
appearance and colour of the rings.  
A summary table, listing and scatter plot of the residual levels of dapivirine in the last 
three rings returned by these participants prior to HIV-1 seroconversion will be 
produced and compared visually with the average ring residual levels of those 
participants who remained HIV-negative over the duration of the trial. If possible, the 


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summary table and plot will also be produced by categories of the appearance and 
colour of these rings. 
Finally, a summary table, listing and scatter plot of the residual levels of dapivirine in 
the last two rings prior to the first positive HIV-1 RNA will be produced and compared 
visually with the average ring residual levels of those participants who remained HIV-
negative over the duration of the trial. 
9.3 
Secondary Endpoints 
9.3.1 
Secondary Endpoint 1: HIV-1 seroconversion rate per 100 person-
years of product use  
Consistent with secondary objective 1, secondary endpoint 1 is the HIV-1 
seroconversion rate per 100 person-years of product use at the end of the vaginal ring 
use period.   
Assessments 
Trial participants will be tested for HIV-1 infection at all trial visits until the last product 
use visit, and at the exit visit, 1-2 months after ring discontinuation. HIV-1 
seroconversion will be determined per the HIV testing algorithm presented in the  
IPM 032 protocol (Appendix B) and assessed by the Principal investigator or dedicated 
sub-investigator at the research centre and the IPM clinical physician to confirm HIV-
1 seroconversion and estimated point of infection5. The HSMC was established to act 
in advisory capacity as IPM 032 secondary endpoints did not require independent 
evaluation of HIV-1 seroconversions and/or HIV-1 trial endpoints. The HSMC was 
consulted on an ad hoc basis, e.g. regarding inconclusive or atypical HIV test results. 
The point of HIV-1 infection was estimated by performing reverse sequential HIV 
Ribonucleic Acid (RNA) Polymerase Chain Reaction (PCR) testing (on stored samples 
collected at each visit) until a negative test result is achieved.  
Statistical methods 
Participants who are not diagnosed with HIV-1 using seroconversion testing at the end 
of the trial participation period will be censored at the last HIV-1 test date, at or prior 
to the last product use visit.  
If HIV-1 is detected at the Exit visit, HIV-1 RNA PCR testing will be performed on stored 
samples in reverse sequential order to estimate the time point of HIV-1 infection.  
• 
If HIV-1 infection is detected at or prior to the last product use visit, the participant 
will be included in the analysis as an HIV-1 seroconverter.  
• 
If the time of infection is determined to be after completion of product use, the 
participant will be censored on the last HIV-1 test date at or prior to the last product 
use visit.  


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This analysis (Analysis 1) will be performed on the m-ITT population, as well as on the 
PP population.  
Three additional analyses of HIV-1 seroconversion rate will be performed: 
• 
Analysis 2: In instances where it cannot be ruled out that HIV-1 infection may 
have occurred during IP use due to atypical/inconclusive HIV RNA PCR test 
results or extended periods of non-product use, such participants will be 
considered as HIV-1 infected on product in this analysis. 
• 
Analysis 3: All confirmed HIV-1 seroconverters determined to have been  HIV-
1 infected after enrollment will be considered as infected on product, even in 
instances where HIV-1 seroconversion and estimated point of infection was 
determined to be after the last product use visit. 
• 
Analysis 4 (HIV-1 infection rate): Similar to Analysis 1, but based on time to 
first positive HIV-1 RNA.  
All additional analyses will be performed on the m-ITT population. 
For the number of participants included in the m-ITT analysis in IPM 032, matching 
placebo participants will be resampled with replacement from the IPM 027 trial, based 
on research center, age and STI prevalence at screening. These factors were selected 
because of their strong association with HIV incidence. 
Age categories (18-24, and ≥ 25 years) will be used to ensure that a sufficient number 
of participants are represented in each combination of categories of age, center and 
STI prevalence at screening (Yes/No). This resampling will be repeated 10 000 times; 
by ordering the 10 000 incidence rates and taking the 250th and 9750th value, a 95% 
confidence interval can be established. The placebo ring data of the complete double-
blind period of IPM 027 will be used for this simulation. 
The incidence of HIV-1 seroconversions, the incidence density rate of HIV-1 
seroconversion (i.e. HIV-1 seroconversion rate per 100 person-years of product use 
at the end of the ring use period) as well as a 95% confidence interval for the HIV-1 
seroconversion rate per 100 person-years (based on the normal approximation of the 
Poisson distribution) may be presented for the simulated placebo and treatment arm, 
overall and for each research centre. Similarly, the incidence of HIV-1 
seroconversions, the incidence density rate and 95% CI will be presented by visit 
schedule (A, B or C) and overall. The 95% CI will be calculated using the formula 
below: 
95% confidence interval = [(n/PY) ± 1.96 x ([n/PY] / PY)½] x 100    
where:  
n = number of HIV-1 seroconversions 


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PY = total number of person-years of product use  
Kaplan-Meier curves, of time to HIV-1 seroconversion will be presented, overall and 
by research centre using PROC LIFETEST in SAS®. 
The time to event will be calculated as follows: 
Time to event (days) = (Date of seroconversion/Censoring Date – Date of first 
ring use) + 1 
Individual participant profiles for participants that seroconverted (listings and/or 
graphical presentations) may be produced, including potential prognostic factors (age, 
marital status, number of male partners, presence of STIs at baseline, number of sex 
acts, condom use during last round of vaginal sex, anal sex since last visit), occurrence 
of urogenital AEs, dapivirine ring residual levels over time, colour and appearance of 
returned rings, the estimated point of HIV-1 infection, and point of HIV-1 
seroconversion. 
9.3.2 
Secondary Endpoint 2: HIV-1 drug resistance mutations among 
participants who acquire HIV-1 
Consistent with the secondary objective to evaluate HIV-1 drug resistance mutations 
among participants who acquire HIV-1 in the trial, secondary endpoint 2 is the 
proportion of HIV-1 seroconverters with drug resistant mutations. 
Assessments 
HIV viral genotyping will be performed on all HIV-1 seroconverters. 
Statistical methods 
The analysis of HIV-1 drug resistance will be primarily descriptive in nature, and will 
depend on the pattern of resistance-associated mutations (RAMs) observed in the 
HIV-1 seroconverters. The Stanford NNRTI Resistance Mutation Scores of Drug 
Resistance Mutations in HIV-1 (database version 8.4 - dated 2017-06-16) is provided 
in Appendix 4. 
The number of RAMs observed will be listed by participant, and a frequency tabulation 
of individual RAMs associated with the various classes of antiretrovirals 
(Protease Inhibitors [PIs], Nucleoside Reverse Transcriptase Inhibitors [NRTIs] and 
Non-nucleoside Reverse Transcriptase Inhibitors [NNRTIs]) will be produced. The 
proportion of HIV-1 seroconverters with at least one HIV-1 drug resistant mutation will 
be presented overall, and by research centre, if possible, with corresponding 95% 
confidence intervals (using the Fisher's exact test).  
If the data allows, the following frequency tabulations will be created: 
• 
The number (and percentage) of participants who had a resistance test 
performed (pre-seroconversion, at seroconversion and at the Exit visit.) 


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• 
Reasons why a resistance test was not performed (if available in the 
database.) 
• 
The number (and percentage) of participants with each individual mutation by 
class (NNRTI, NRTI, major PI.) 
• 
The number (and percentage) of participants with 0, 1, 2, and ≥ 3 mutations 
by class (NNRTI, NRTI, major PI.) 
• 
The number (and percentage) of participants with different mutational patterns 
(including single mutations), by class (NNRTI, NRTI, major PI.) 
• 
Additional mutations (e.g. those selected by dapivirine in vitro but not included 
in the Stanford HIV database set) will be described. 
In addition, for each NNRTI drug, the resistance mutation scores for NNRTIs efavirenz, 
etravirine, nevirapine and rilpivirine, will be calculated according to the Stanford 
database version 8.4, dated 2017-06-16 (see Appendix 4), per genotype by summing 
the individual scores associated with individual mutations (and the additional scores 
for combinations of mutations where applicable.) Based on the resistance mutation 
score, virus from participants will be classified as susceptible, potential low-level 
resistant, low-level resistant, intermediate resistant or high-level resistant for each 
NNRTI drug, based on the following cut-offs: 
NNRTI resistance 
mutation score 
Level of resistance 
<10 
Susceptible 
10 - <15 
Potential low-level 
resistant 
15 - < 30 
Low-level resistant 
30 - < 60 
Intermediate resistant 
≥ 60 
High-level resistant 
For each approved NNRTI drug (efavirenz, etravirine, nevirapine and rilpivirine), 
descriptive statistics will be presented on the total NNRTI resistance mutation score 
and a frequency tabulation will be presented on the resistance level.  
Note: Only results at time of HIV-1 seroconversion will be included in tabulations. 
Listings of all individual data will be created and will include all participant resistance 
assessments. 
These analyses will be performed overall, by HIV-1 RNA level at HIV-1 seroconversion  
(≥ 2000 copies/mL , < 2000 copies/mL), treatment schedule (A, B or C) and by HIV-1 
subtype (C, other). 


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There will be an additional analysis to determine the number and timing of samples 
analysed prior to and after HIV-1 seroconversion. Any changes of genotype between 
the prior- and after- HIV-1 seroconversion samples will be described. 
Finally, the primary analysis will be repeated for the Virology Population, for all 
samples analysed at any time during the period of the first positive HIV-1 RNA visit 
and the Exit visit.  This is to ensure that all mutations are accounted for. 
9.4 
Exploratory Endpoints 
9.4.1 
Exploratory Endpoint 1: Participant report of feasibility of 3-monthly 
clinical follow-up schedule 
Consistent with exploratory objective 1, exploratory endpoint 1 is the participant report 
of feasibility regarding a 3-monthly clinical follow-up schedule (Participant 
Questionnaire). 
Assessments 
Participants will complete a Participant Questionnaire at all trial visits until the last 
product use visit. In particular, the following items will be captured: 
Participant Questionnaire Part A (month 1, 2 and 3): 
Item 1: As per investigator decision are you coming to the research centre next month 
or in three months for your next visit? 
Item 2: Will you take your extra rings with you today or will you come back to the 
research centre each month to pick up your new ring? 
Item 3: What are your reasons for leaving the rings at the research centre today? 
Participant Questionnaire Part B (month 2 and 3): 
Item 10: If you were not in a study, would you prefer to come to the health care clinic 
/ provider for new rings each month, or every three months?  
Item 11: If you were not in a study, would you prefer to come to the health care clinic 
/ provider for an HIV test each month, or every three months? 
Participant Questionnaire (3 month follow-up): 
Item 1: Will you take your extra rings with you today or will you come back to the 
research centre each month to pick up your new ring? 
Item 2: What are your reasons for leaving the rings at the research centre today? 
Item 16: If you were not in a study, would you prefer to come to the health care clinic 
/ provider for new rings each month, or every three months?  
Item 17: If you were not in a study, would you prefer to come to the health care clinic 
/ provider for an HIV test each month, or every three months? 
Participant Questionnaire (last product use visit): 


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Item 1: When you were doing your three monthly visits, did you take your extra rings 
with you or did you come back to the research centre each month to pick up your new 
ring? 
Item 2: What were your reasons for leaving the rings at the research centre? 
Item 16: If you were not in a study, would you prefer to come to the health care clinic 
/ provider for new rings each month, or every three months?  
Item 17: If you were not in a study, would you prefer to come to the health care clinic 
/ provider for an HIV test each month, or every three months? 
At all trial visits and the last product use visit, the RL CRF will be completed, indicating 
the rings dispensed at each trial visit (items 1 and 2) and the used / unused rings 
returned at each trial visit (items 7 and 8). 
Statistical methods 
The analysis of feasibility of the 3-monthly clinical follow-up schedule will be primarily 
descriptive in nature, and will include absolute and relative frequencies for each trial 
visit for Participant Questionnaire items listed above, overall and by Visit Schedule (A, 
B or C). In particular, the number and percentage of women opting not to receive two 
additional rings at the 3-monthly clinical follow-up schedule will be reported.  
The proportion of returned rings (used and unused) during the 3-monthly clinical 
follow-up schedule will also be reported. This will be calculated as the number of 
used/unused rings returned divided by the number of rings dispensed. 
9.4.2 
Exploratory Endpoint 2: Correlation between dapivirine residual 
amounts in returned used vaginal rings and/or drug concentrations, 
and results from visual inspection of returned vaginal rings 
Consistent with exploratory objective 2, exploratory endpoint 2 is the dapivirine ring 
residual levels in returned used vaginal rings and/or dapivirine concentrations in 
plasma and/or vaginal fluid (not assayed) in correlation with results from the visual 
inspection of the returned used vaginal rings by research staff.  
Assessments 
At all trial visits and the last product use visit, the RL CRF will be completed, indicating 
the rings dispensed at each trial visit (items 1 and 2) and the appearance of 
used/unused rings returned at each trial visit (items 7, 8 and 9).  
Residual levels of dapivirine in used rings will be determined for all participants 
receiving IP at each trial visit. 
Statistical methods 
The correlation between the amount of corrected residual dapivirine in the used 
vaginal rings and the corresponding results from the visual inspection of the returned 
used vaginal rings, will be explored descriptively by producing summary statistics and 


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a corresponding scatter plot of the dapivirine levels for each category of appearance 
and colour of the returned ring.  
9.4.3 
Exploratory Endpoint 3: Proportion of participants opting for HIV rapid 
tests at the research centre between scheduled 3-monthly visits 
Consistent with exploratory objective 3, exploratory endpoint 3 is the proportion of 
participants opting for HIV rapid tests at the research centre between scheduled 3-
monthly research centre follow-up visits.  
Assessments 
Trial participants will have HIV rapid tests performed at the research centre at all trial 
visits until the last product use visit, and at the exit visit, 1-2 months after ring 
discontinuation, and as needed. 
Statistical methods 
The proportion of participants undergoing HIV rapid tests at the research centre 
between scheduled 3-monthly follow up visits will be calculated as the number of 
participants with at least one HIV rapid test performed at an unscheduled visit divided 
by the total number of participants with at least one HIV rapid test performed at any 
visit.  
9.4.4 
Exploratory Endpoint 4: Self-reported acceptability and adherence to 
vaginal ring use 
Consistent with exploratory objective 4, exploratory endpoints 4 and 5 are the 
proportion of participants who respond positively to questions on ring acceptability at 
the last product use visit, and participant self-reported patterns of ring use, 
respectively. 
Assessments – Self-reported acceptability 
Participant questionnaires will be administered at every trial visit after enrollment, until 
the last product use visit. 
Statistical methods – Self-reported acceptability 
The proportion of participants among all trial participants who respond positively (i.e. 
Yes) to the following two questions at the last product use visit:  
• 
“Do you think it is possible for women to use the ring as requested (i.e. without 
removing it)?” 
• 
“Do you think women in your community would want to use this ring if it were 
available?” 
A participant will be classified as having found the vaginal ring acceptable if she 
responds positively to the first question, about keeping the ring inserted as prescribed. 
Community acceptability will be demonstrated by positive responses to the second 
question. For each question, the proportion of participants who responded positively, 


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and the corresponding Fisher’s exact 95% confidence interval, will be calculated and 
presented.  
Summary tables with descriptive statistics will be presented for the socio-demographic 
variables and psycho-social variables collected in the participant questionnaires. 
Note: Additional explanatory analyses will utilise the qualitative data from focus group 
discussions and individual interviews; these analyses will be performed separately 
from the analyses described in this analysis plan, and will be discussed in the Clinical 
Study Report. 
Assessments – Self-reported adherence 
Information on rings dispensed and returned are recorded at each trial visit on the RL 
CRF. Participant self-reports of accidental ring expulsions and removals are recorded 
on the EXP CRF. 
Statistical methods – Self-reported adherence 
Self-reported adherence to the ring regimen will be calculated per visit, and presented 
descriptively overall and by research centre. The adherence rate per visit will be 
calculated as:  
• 
100 x (number of days that the participant reportedly wore the ring / the total 
number of days that the participant was expected to wear the ring). 
The number of days that the participant reportedly wore the ring is based on data 
captured in the Ring Insertion/Removal Log (RL) CRF and the EXP CRF at the 
scheduled visit and any preceding unscheduled visit between the current and the 
previous scheduled visit. The total number of days that the participant was expected 
to wear the ring is a calendar month (30 days) from the insertion date. 
The self-reported adherence rates will be presented in the following categories: 
• 
≥ 90% 
• 
≥ 80% to < 90% 
• 
< 80%. 
Summary tables with descriptive statistics will be presented for accidental ring 
expulsions and removals by the participant for reasons other than instructed by the 
research centre staff. 
10 EVALUATION OF SAFETY PARAMETERS 
10.1 
Adverse Events 
An AE is defined as any untoward medical occurrence in a clinical trial participant. An 
AE can therefore be any unfavourable and unintended sign (including an abnormal 


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laboratory assessment finding), symptom or disease temporally associated with the 
participation in this trial, whether or not considered related to the IP. All AEs will be 
coded using MedDRA (Version 19.0). 
10.1.1 
Treatment Emergent Adverse Events (TEAEs) 
TEAEs are defined as AEs which occurred/worsened after the first insertion of the IP, 
up to six weeks after last ring use.  
10.1.2 
Product-related Adverse Events 
Product-relatedness is reported as “Related” or “Not Related”. While every effort is 
made to ensure that this field is not missing through data reviews and queries, if the 
relationship with the IP is missing on the CRF, it will be assumed that the AE was 
“Related” to the IP.   
Summary Tables 
A summary table of TEAEs will be presented, indicating the frequency and proportion 
of participants with: 
• 
At least one TEAE 
• 
At least one serious TEAE 
• 
At least one Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 
or 4 TEAE 
• 
At least one product-related TEAE 
• 
At least one serious product-related TEAE 
• 
A TEAE leading to death 
• 
A TEAE leading to premature (permanent) IP discontinuation 
• 
A TEAE leading to temporary IP discontinuation 
• 
A TEAE leading to trial discontinuation. 
If meaningful, the same summary tables may be produced for non-TEAEs.  
The definitions and location of data elements to be used to define each measure are 
described in Table 2 below. 
Table 2 Definition and Data Sources of AEs 
Measure 
Statistic 
Data Sources* 
Participants with at 
least one TEAE 
Frequency 
A participant reported with an AE in the AE 
CRF 
Source: AE 
Participants with at 
least one serious 
TEAE 
Frequency 
A participant reported as having an SAE per 
the AE CRF  
Source: AE   


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Measure 
Statistic 
Data Sources* 
Participants with at 
least one DAIDS 
Grade 3 or 4 TEAE 
Frequency 
A participant reported as having a DAIDS 
Grade 3 or 4 AE 
Source: AE 
Participants with at 
least one product-
related TEAE 
Frequency 
A participant reported as having a “related” 
event, per the AE CRF  
Source: AE   
Participants with at 
least one serious 
product-related TEAE 
Frequency 
A participant reported as having a “related” 
SAE, per the AE CRF  
Source: AE   
Participants with a 
TEAE leading to 
death 
Frequency 
A participant reported as having an AE with 
the reported outcome “fatal” per the AE CRF  
Source: AE   
Participants with a 
TEAE leading to 
premature 
(permanent) IP 
discontinuation 
Frequency 
A participant reported as having an AE with an 
action taken of “drug withdrawn” per the AE 
CRF  
Source: AE   
Participants with a 
TEA leading to 
temporary IP 
discontinuation 
Frequency 
A participant reported as having an AE with an 
action taken of “drug interrupted” per the AE 
CRF  
Source: AE   
Participants with a 
TEAE leading to trial 
discontinuation 
Frequency 
A participant reported as having a Trial 
Completion status of “Participant discontinued 
from the trial early” and a reason of “Adverse 
event/intercurrent illness” per the TC CRF  
Source: TC   
* Percentages will use the total number of enrolled participants as denominator. 
A by-participant listing of all TEAEs will include the variables in Table 3 below.  
Table 3 AE Variables 
Variable 
Data Type 
Data Sources 
SAE 
Dichotomous 
Yes/No 
Source: AE  
Outcome 
Nominal 
Fatal, Not recovered/not resolved, 
Recovering/resolving, Resolved/recovered w/sequelae, 
Recovered/resolved, Unknown 
Source: AE  
Severity 
Ordinal 
Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, 
Grade 4 Potentially life-threatening, Grade 5 Death 
Source: AE  
Relationship Ordinal 
Related, Not related 
Source: AE  
Action 
Nominal, 
DDMMMYY 
Dose not changed, Drug interrupted, Drug withdrawn, 
N/A 
Date interrupted, date reintroduced, date withdrawn 


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Variable 
Data Type 
Data Sources 
Source: AE 
Other action 
Nominal 
None, Treatment medication, Non-drug therapy, Other 
Source: AE 
SOC 
Nominal 
System Organ Class  
Source: AE  
PT 
Nominal 
Preferred Term 
Source: AE  
AE Term 
(Verbatim) 
Nominal 
Reported Event  
Source: AE 
The incidence of TEAEs will be presented by SOC and PT, overall, IPM 027 treatment 
arm and by research centre. 
The incidence of the following TEAEs by severity will be presented by SOC and PT, 
overall, IPM 027 treatment arm and by research centre: 
• 
TEAEs 
• 
Serious TEAEs 
• 
Product-related TEAEs 
• 
Serious product-related TEAEs 
• 
Social harms reported as TEAEs (refer to Section 10.9). 
In addition, for IPM 027 participants who directly enrolled in the IPM 032 trial from the 
open-label treatment period of IPM 027, a subgroup display of Overall TEAEs, TEAEs 
by worst severity and Product-related TEAEs will be presented. 
Maximum severity will be assumed for an AE with missing severity. 
A by-participant listing of all deaths, SAEs, non-TEAEs, permanent IP discontinuations 
and premature trial discontinuations will be presented in Appendix 16 of the CSR. 
These by-participant listings will include variables described in the summary of TEAEs 
in addition to the following variables: 
Table 4 Additional AE Variables 
Variable 
Data Type 
Data Sources 
AE start date 
DDMMMYY 
Start date 
Source: AE 
Outcome 
date 
DDMMMYY 
Outcome date 
Source: AE 
Trial day 
Continuous 
Trial day = (Start Date of AE – Date of First Use of IP) + 
1 
Source: Calculated from AE (AESTDAT) and ENR 


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Variable 
Data Type 
Data Sources 
(TCDAT)  
Duration 
(days) 
Continuous 
Duration (days) = AEENDAT – AESTDAT +1 
Source: Calculated from AE 
Duration will only be calculated if both the start and stop 
dates are available, or if the start date is known and the 
AE is ongoing at trial end; in such cases, the duration will 
be reported as “> (Trial Termination Date – Start Date of 
AE) + 1” 
10.2 
Clinical Laboratory Evaluation 
Collection of blood and urine specimens for haematology (including full blood counts, 
differential and platelet count), biochemistry (including creatinine, Aspartate 
Aminotransferase [AST] and Alanine Aminotransferase [ALT]) and urinalysis tests 
(urine dipstick analysis and urine microscopy if clinically indicated) is conducted at 
Screening or any other trial visit if clinically indicated. For the South African research 
centres, clinical laboratory assessments are performed by a central laboratory, and for 
the Uganda research centre, by the research centre's certified laboratory. In 
accordance, reference ranges are provided by the central laboratory and local 
laboratory, respectively. 
Listings of all clinical laboratory data for each participant will be provided. Laboratory 
test results will be categorised by DAIDS Grade, and clinical significance. Specific 
haematology, biochemistry, urinalysis, and microscopy parameters assessed during 
the trial are listed below.   
Table 5 Haematology, Biochemistry, Urinalysis and Microscopy Parameters 
Haematology 
(continuous)1 
Biochemistry 
(continuous)1 
Urinalysis (continuous) 
     Erythrocytes 
     Haemoglobin 
     Haematocrit 
     Platelets 
     Leukocytes 
     Neutrophils 
     Lymphocytes 
     Monocytes 
     Eosinophils 
     Basophils 
      
Electrolytes  
     Sodium 
     Potassium 
     Chloride 
     Calcium 
     Phosphate 
Liver Function 
     Bilirubin 
     Alkaline phosphatase 
     ALT 
     AST 
Renal Function 
     Urea 
     N/A 
Urinalysis (categorical) 
     Protein 
     Glucose 
      
Microscopy (categorical) 
     White blood cells (WBC) 
     Red blood cells (RBC) 
      
 
                                               
1 Graded according to the DAIDS table1 (Grades 1-4). 


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Haematology 
(continuous)1 
Biochemistry 
(continuous)1 
Urinalysis (continuous) 
     Creatinine 
Data sources: Haematology and biochemistry reported in HAE and CHEM CRFs; 
urinalysis and microscopy reported in UTR CRF. 
Additionally, a listing of all abnormal clinical laboratory data will be provided. 
10.3 
Pelvic examinations 
10.3.1 
Assessments 
Pelvic examinations will be performed at Screening and the last product use visit, or 
at any visit if clinically indicated. 
10.3.2 
Summary Tables 
A summary of pelvic examinations will be presented for the all scheduled trial visits, 
overall, IPM 027 treatment arm and by research centre in tabular form. By-participant 
listings will also be provided. The summary tables and listings will include the variables 
in Table 6 below. 
Table 6 Pelvic Examination Variables 
Variable 
Data Type 
Data Sources 
Presence of 
Vulvar findings 
Categorical 
Source: PEL 
Indicator variable for: Vulvar erythema, vulvar edema, 
vulvar rash, vulvar tenderness, Bartholin’s or Skene’s 
gland abnormality 
Presence of 
Vaginal findings 
Categorical 
Source: PEL  
Indicator variable for: Vaginal erythema, vaginal 
edema, vaginal masses, vaginal abrasions or 
lacerations, vaginal tenderness, vaginal discharge 
Presence of 
Cervical 
findings 
Categorical 
Source: PEL 
Indicator variable for: Cervical erythema, cervical 
edema and/or friability, cervical masses, cervical 
motion tenderness, cervical discharge 
General/other 
findings 
Categorical 
Source: PEL 
Indicator variable for: Odour, uterine masses, adnexal 
masses, uterine tenderness, adnexal tenderness, 
condyloma, abnormal genital tract bleeding, other 
Presence of 
Vulvar Lesions 
findings 
Categorical 
Source: PEL 
Indicator variable for: Ulcer, blister, pustule, peeling, 
ecchymosis, other lesions 
Presence of 
Vaginal Lesions 
findings 
Categorical 
Source: PEL 
Indicator variable for: Ulcer, blister, pustule, peeling, 
ecchymosis, other lesions 
Presence of 
Cervical 
Lesions findings 
Categorical 
Source: PEL 
Indicator variable for: Ulcer, blister, pustule, peeling, 
ecchymosis, other lesions 
Cervical ectopy 
Categorical 
Source: PEL 


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10.4 
Cervical cytology 
10.4.1 
Assessments 
A cervical cytology sample will be collected at Screening (if not done in the previous 
year or if the result was abnormal at the last point of testing) and as needed.  
10.4.2 
Summary Tables 
A summary of the cervical cytology results will be presented overall, IPM 027 treatment 
arm and by research centre, for the Screening visit. By-participant listings will also be 
provided for all visits. The summary tables and listings will include the following 
variables: 
Table 7 Cervical Cytology Variables 
Variable 
Data Type 
Data Sources 
Cervical 
cytology result 
Categorical 
Source: CR 
Indicator variable for: Negative for intraepithelial lesion 
or cancer (malignancy), ASCUS, SIL-low grade (LSIL), 
ASC-H, SIL-high grade (HSIL), AGC, AGC-favor 
neoplastic, cancer, other findings 
10.5 
STI assessments 
10.5.1 
Assessments 
Cervicovaginal samples will be collected for STI testing (Trichomonas, Gonorrhoea, 
and Chlamydia) at Screening and at the last product use visit, or any other trial visit as 
clinically indicated. At Screening, blood will be collected for Syphilis (RPR) testing. 
TPHA/TPPA testing will be performed if the RPR is reactive.  
10.5.2 
Summary Tables 
STI results will be presented for the Screening and last product use visits, overall, IPM 
027 treatment arm and by research centre. Variables that will be summarised in the 
tables and listings include: 
Table 8 STI Variables 
Variable 
Data Type 
Data Sources 
Trichomonas rapid Test 
Dichotomous 
Source: STI 
Gonorrhoea 
Dichotomous 
Source: STI 
Chlamydia 
Dichotomous 
Source: STI 
Syphilis RPR screening test 
Dichotomous 
Source: STI 
Syphilis RPR titre 
Discrete 
Source: STI 
Syphilis confirmatory test 
TPHA/TPPA 
Categorical 
Source: STI 
Blood present during 
collection of cervico-vaginal 
samples 
Dichotomous 
Source: STI 


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10.6 
Immediately Reportable Events 
In addition to SAEs, the following events are considered immediately reportable events 
(IREs): 
1) Pregnancy 
2) HIV-1 seroconversion  
3) Any non-serious AE leading to permanent discontinuation of the IP 
10.6.1 
Assessments 
Urine pregnancy tests will be conducted at all scheduled trial visits, except for the Exit 
visit, and can be performed additionally at unscheduled visits as needed. Serum 
pregnancy tests will be performed at the Investigator’s discretion. A negative serum 
test after a positive urine test would overrule the positive urine test. 
HIV rapid tests will be performed at the research centre at all trial visits until the last 
product use visit, and at the exit visit, 1-2 months after ring discontinuation, and as 
needed. HIV RNA PCR samples will be collected at the Screening and Enrollment 
visits and at all trial visits, but will only be analysed if there is reason to believe that the 
participant is HIV-positive.  
All AEs (serious and non-serious) are monitored throughout the trial; analysis of AEs 
is discussed in Section 10.1.  
10.6.2 
Summary Tables 
Results from pregnancy tests will be presented in tabular form overall, by IPM 027 
treatment arm and by research centre for each trial visit and will include appropriate 
statistics. A table including the following summaries will be included: 
• 
Proportion of pregnancies 
• 
Pregnancy incidence rates by contraceptive method (DMPA, norethisterone, 
oral contraception, etc.)  
• 
Pregnancy incidence rates by outcome (full term live birth, premature term live 
birth, etc.).  
• 
Pregnancy incidence rates per 100 person-years 
• 
Frequencies of congenital anomalies  
By-participant listings will be provided for each participant. 
Table 9 Pregnancy Tests 
Variable 
Data Type 
Data Sources 
Type of test (urine or 
serum) 
Dichotomous 
Source: PHTR  


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Statistical Analysis Plan, Draft, Version 1.0 
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Pregnancy Test 
Dichotomous 
Source: PHTR  
Results from HIV tests will be presented in tabular form overall, by IPM 027 treatment 
arm and by research centre for each trial visit and will include appropriate statistics. 
By-participant listings will be provided for each participant, including whether the 
participant HIV-1 seroconverted (confirmed), the date of seroconversion, the time to 
seroconversion, and whether HIV-1 infection occurred while using IP.  
Table 10 HIV Tests 
Variable 
Data Type 
Data Sources 
HIV Test Result (Test #1) 
Dichotomous 
Source: PHTR 
HIV Test Result (Test #2) 
Dichotomous 
Source: PHTR 
HIV Test Result (Test #3) 
Dichotomous 
Source: PHTR 
HIV-1 Western Blot 
Nominal 
Source: SER  
Repeat HIV-1 Western 
Blot  
Nominal 
Source: SER  
HIV-2 Western Blot 
Nominal 
Source: SER  
Repeat HIV-2 Western 
Blot  
Nominal 
Source: SER  
RNA PCR Testing 
Nominal 
Source: electronic lab data  
*Only tested for HIV-1 seroconverters 
10.7 
Concomitant Medications 
Concomitant medication is defined as any medication taken in conjunction with the IP, 
i.e. medication that either: 
1) Started after the first insertion of the IP, or 
2) Started before the first insertion of the IP, but ended on or after the first insertion 
of the IP. This includes medication indicated as “Ongoing” at the end of the trial.   
Concomitant medications will be coded using the WHO DDE (version June 2017); a 
table displaying the frequency and proportion of participants using medications during 
the trial overall, by research centre, and by ATC level 2 and preferred name, will be 
presented. Concomitant medication will also be presented in the form of listings which 
will contain information for each medication used. 
Table 11 Concomitant Medication Variables 
Variable 
Data Type 
Data Sources 
Drug Name 
Text  
Verbatim; Source: CM, CMTRT_1-3 
ATC category 
Text 
Verbatim; Source: CM, ATCCode1-3 
Indication 
Text  
Verbatim; Source: CM, CMINDC_1-3 
Dose/Unit 
Text 
Verbatim; Source: CM, CMDOSE_1-3 
Route 
Text 
Verbatim; Source: CM, CMRTE_1-3 
Frequency 
Text 
Verbatim; Source: CM, CMDSFQ_1-3 


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Statistical Analysis Plan, Draft, Version 1.0 
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Start date 
DDMMMYY 
Source: CM, CMSTDT_1-3 
Stop date 
DDMMMYY 
Source: CM, CMENDT_1-3 
Ongoing at last visit 
Dichotomous 
Source: CM, CMONGO_1-3 
10.8 
Physical Examination Findings and Vital Signs 
A physical examination will be conducted at Screening and at the last product use visit. 
At these visits, vital signs will be recorded and body systems will be evaluated for 
abnormal/normal findings, with the exception of Height, which will only be measured 
at Screening. For vital signs, the observed data and the absolute change from baseline 
(Screening) will be summarised overall and by research centre using appropriate 
descriptive statistics, as described in Section 6.6.  Listings of all vital signs data will be 
provided.  
Data from physical examination findings will be listed only. 
Variables that will be summarised in the listings include: 
Table 12 Physical Examination and Vital Signs Parameters 
Variable 
Data Type 
Data Sources 
Height 
Continuous 
Source: PX (Screening) 
Weight 
Continuous 
Source: PX 
BMI 
Continuous 
Derived: 
weight(kg)/height(m)2, 
rounded to 1 decimal 
Temperature 
Continuous; Dichotomous 
Source: PX 
Pulse 
Continuous; Dichotomous 
Source: PX 
Respiratory rate 
Continuous; Dichotomous 
Source: PX 
Blood pressure 
Continuous; Dichotomous 
Source: PX 
 
General Examination of 
Body Systems: 
 
 
General appearance, 
gastrointestinal/abdomen, 
neck, lymph nodes, 
cardiovascular/heart, 
respiratory/lungs, 
musculoskeletal/extremities, 
neurological, skin, eyes, 
ear/nose/throat, and other 
(1-3). 
Nominal 
Source: PX 
10.9 
Social Harms 
During each HIV counselling session, participants will be asked questions to assess 
the occurrence of social harms related to trial participation. Participants who 
experience social harms related to trial participation will be counselled accordingly and 


IPM 032 
Statistical Analysis Plan, Draft, Version 1.0 
Version Dated: 29 Mar 2019 
 Page 39 of 39 
provided with assistance to mitigate the circumstances, if possible. This will be 
recorded in the source documents and applicable CRFs. 
By-participant listings of all social harms data will be provided as well as summary 
tables of such occurrences. Social harms that were reported as AEs, as well as all 
occurrences of sexual assault (whether associated with physical injury or not), will be 
summarised by SOC and PT, and by severity (refer to Section 10.1). 
11 CHANGES IN THE PROTOCOL-PLANNED ANALYSES  
There are no changes to the protocol-planned analyses.  
12 REFERENCES 
1. Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, 
Version 1.0 December, 2004; Clarification 1 August 2009. 
2. ICH (1996). International Conference on Harmonisation. Guideline E3 Structure and 
Content of Clinical Trial Reports. 
3. ICH (1998). International Conference on Harmonisation. Guideline E9 Statistical 
Principles for Clinical Trials. 
4. IPM 032 Protocol: A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED 
SAFETY OF AND ADHERENCE TO THE DAPIVIRINE (25 mg) VAGINAL RING-004 
IN HEALTHY, HIV-NEGATIVE WOMEN Version 2.0, Amendment 1.0; 22 October 
2015. 
5. IPM 032 Protocol: A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED 
SAFETY OF AND ADHERENCE TO THE DAPIVIRINE (25 mg) VAGINAL RING-004 
IN HEALTHY, HIV-NEGATIVE WOMEN Version 2.0, Amendment 2.0; 16 January 
2016. 
13 APPENDICES 
13.1 
Appendix 1 – Table Shells 
13.2 
Appendix 2 – Figure Shells 
13.3 
Appendix 3 – Individual Participant Listing Shells 
13.4 
Appendix 4 –  Stanford HIV-1 Drug Resistance (database version 8.4 
– dated 2017-06-16) 
13.5 
Appendix 5 – Adverse events of special interest 
13.6 
Appendix 6 – Implemented Sections of IPM 032 Protocol V2.0 
Amendment 2.0, dated 16 January 2016 
13.7 
Appendix 7 – Protocol deviation criteria                    
        
 


 
 
 
 
 
 
 
 
IPM 032 
Statistical Analysis Plan, Version 1.0 
Version dated: 29 March 2019 
 
13 APPENDICES  
 
TABLE OF CONTENTS 
 
• 13.1 Appendix 1 – Table Shells  
• 13.2 Appendix 2 – Figure Shells  
• 13.3 Appendix 3 – Individual Participant Listing Shells  
• 13.4 Appendix 4 – Stanford HIV-1 Drug Resistance (database version 8.4 – dated 
16 June 2017)  
• 13.5 Appendix 5 – Adverse Events of Special Interest  
• 13.6 Appendix 6 – Implemented Sections of IPM 032 Protocol V2.0 Amendment 
2.0, dated 16 January 2016  
• 13.7 Appendix 7 – Protocol Deviation Criteria 


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IPM 032 
 
 
 
TABLES – VERSION 1.0, 26 MAR 2020 


 TABLE SHELLS                                                                         
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14.1 
Demographic Data 
14.1.1 
Disposition  
14.1.1.1 
Disposition of Participants by Visit Schedule 
14.1.1.2 
Analysis Population Assignment 
14.1.1.3 
Protocol Deviations  
14.1.2 
Demographics 
14.1.2.1 
Demographics at Screening by IPM 027 Treatment Arm 
14.1.2.2 
Demographics at Screening by Enrolled Status (from IPM 027) 
14.1.3 
Baseline Characteristics 
14.1.3.1 
Medical History at Screening 
14.1.3.2 
Contraceptive/ Menstrual/ Obstetric History at Screening 
14.1.3.3 
Gynaecological History at Screening 
14.1.3.4 
Prior Medication  
14.2 
Efficacy Data 
14.3 
Safety Data 
14.3.1 
Display of Adverse Events 
14.3.1.1 
Overall Summary of Treatment Emergent Adverse Events 
14.3.1.2 
Treatment Emergent Adverse Events by System Organ Class and Preferred Term 
14.3.1.3 
Product-Related Treatment Emergent Adverse Events by System Organ Class and 
Preferred Term 
14.3.1.4 
Grade 3 or 4 Treatment Emergent Adverse Events by System Organ Class and 
Preferred Term 
14.3.1.5 
Serious Treatment Emergent Adverse Events by Primary System Organ Class and 
Preferred Term 
14.3.1.6 
Urogenital Treatment Emergent Adverse Events Primary System Organ Class and 
Preferred Term 
14.3.1.7 
Treatment Emergent Adverse Events by Worst Severity, Primary System Organ 
Class and Preferred Term 
14.3.1.8 
Serious Treatment Emergent Adverse Events by Worst Severity, Primary System 
Organ Class and Preferred Term 
14.3.1.9 
Product-Related Treatment Emergent Adverse Events by Worst Severity, Primary 
System Organ Class and Preferred Term 
14.3.1.10 
Serious Product-Related Treatment Emergent Adverse Events by Worst Severity, 
Primary System Organ Class and Preferred Term 
14.3.1.11 
Social Harms Reported as Treatment Emergent Adverse Events by Worst Severity, 
Primary System Organ Class and Preferred Term 
14.3.2 
Listings of Deaths, Other Serious and Significant Adverse Events 
14.3.3 
Narratives of Deaths, Other Serious and Certain Other Significant Adverse 
Events 
14.3.4 
Abnormal Laboratory Value Listing (Each Patient) 
14.3.5 
Extent Of Exposure, Dosage Information, And Compliance 
14.3.5.1 
Adherence, Overall Summary of Dapivirine Residual Levels (mg) in Used Rings 
14.3.5.2 
Adherence, Summary of Dapivirine Residual Levels (mg) in Used Rings by 
Category 
14.3.5.3 
Adherence, Summary Relating Ring Residual Levels (mg) to Time Intervals 
Between Consecutive Ring Replacements 
14.3.5.4 
Residual Levels of Dapivirine (mg) in the Last Three Rings Returned by Participants 
Who Seroconverted, Prior to HIV-1 Seroconversion 
14.3.5.5 
Self-Reported Adherence to Dapivirine Ring  
14.3.5.6 
Self-Reported Acceptability to Dapivirine Ring 
14.3.5.7 
Accidental Expulsion/ Removal 


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14.3.6 
Vital Signs And Physical Examination 
14.3.6.1 
Vital Signs  
14.3.7 
Other Safety Data 
14.3.7.1 
Pelvic/ Speculum Examinations  
14.3.7.2 
Cervical Cytology at Baseline 
14.3.7.3 
Sexually Transmitted Infections  
14.3.7.4 
Immediately Reportable Events 
14.3.7.5 
Analysis 1, HIV-1 Seroconversion Rate per 100 Person-Years of Product Use   
14.3.7.6 
Analysis 2, HIV-1 Seroconversion Rate per 100 Person-Years of Product Use  
14.3.7.7 
Analysis 3, HIV-1 Seroconversion Rate per 100 Person-Years of Product Use  
14.3.7.8 
Analysis 4, HIV-1 Seroconversion Rate per 100 Person-Years of Product Use  
14.3.7.9 
Overview of Number of Participants in the Trial 
14.3.7.10.1 
Reverse Transcriptase Inhibitor and Protease Inhibitor Resistance-Associated 
Mutations Observed at Seroconversion Timepoint 
14.3.7.10.2 
Reverse Transcriptase Inhibitor and Protease Inhibitor Resistance-Associated 
Mutations Observed at Any Timepoint 
14.3.7.11 
Data Overview of HIV-1 Seroconversion Timing Relative To HIV-1 RNA Detection 
and Treatment 
14.3.7.12 
Overview of HIV-1 RNA and Genotyping Information Availability 
14.3.7.13.1 
Mutational Patterns Observed at Seroconversion Timepoint 
14.3.7.13.2 
Mutational Patterns Observed at Any timepoint 
14.3.7.14.1 
Summary of Mutational Patterns of Resistance-Associated Mutations at 
Seroconversion Timepoint 
14.3.7.14.2 
Summary of Mutational Patterns of Resistance-Associated Mutations at Any 
Timepoint  
14.3.7.15 
Timing Profile 
14.3.7.16 
Pregnancy Test Results 
14.3.8 
Concomitant Medication 
14.3.8.1 
Concomitant Medication  
14.4 
PK Tables 
14.5 
PD Tables 
14.6 
Other Data 
14.6.1 
Participant Report, Feasibility of 3-Monthly Clinical Follow-Up Schedule  
14.6.2 
Correlation Between Dapivirine Residual Levels (mg) and Results From Visual 
Inspection of Returned Vaginal Rings  
14.6.3 
Proportion of Participants Opting for HIV Rapid Tests at the Research Centre 
Between Scheduled 3-Monthly Visits 
14.6.4 
Social Harms  
14.6.5 
Participant Questionnaire – Part A (Month 1, 2, and 3) 
14.6.6 
Participant Questionnaire – Part B (Month 2 and 3 only) 
14.6.7 
Participant Questionnaire – Part C (Month 1, 2, and 3) 
14.6.8 
Participant Questionnaire – 3 Month Follow-Up 
14.6.9 
Participant Questionnaire – Last Product Use Visit 
14.6.10 
Participant Questionnaire - Vaginal Practices 
 
 
 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
Table 14.1.1.1 
Disposition of Participants by Visit Schedule 
All Participants 
 
 
Page 4 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
Schedule  
A 
Schedule  
B 
Schedule  
C 
Unknown 
All  
Schedules 
 
 
 
 
 
 
 
Screened participants 
N 
 
 
 
 
X  
Screen failures 
n (%)a 
 
 
 
 
X (  X.X) 
  Reasons for ineligibility 
 
 
 
 
 
 
    Incl / 
n (%)b 
 
 
 
 
X (  X.X) 
    Excl / 
n (%)b 
 
 
 
 
X (  X.X) 
    Incl and excl 
n (%)b 
 
 
 
 
X (  X.X) 
Participants enrolled 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
Participants who received IP 
n (%)c 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Permanently discontinued IP 
n (%)c 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Permanently discontinued trial 
n (%)c 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Completed trial 
n (%)c 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
Reason for discontinuing trial 
 
 
 
 
 
 
  Non-compliance 
n (%)d 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Lost to follow-up  
n (%)d 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Adverse event/intercurrent illness 
n (%)d 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Inappropriate enrolment 
n (%)d 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  HIV-1 seroconversion  
n (%)d 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Pregnancy 
n (%)d 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Sponsor terminated the trial  
n (%)d 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Death 
n (%)d 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Other 
n (%)d 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Participant withdrew consent  
n (%)d 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Relocation 
n (%)e 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Employment/work  
n (%)e 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Family/partner pressure 
n (%)e 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Other 
n (%)e 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
Excl = Exclusion; HIV-1 = Human immunodeficiency virus type 1; Incl = Inclusion; IP = Investigational product 
Percentages are calculated out of the number of participants (per visit schedule) a Screened b Screen failed  c In the safety population d Non-completed e Withdrew consent 
Visit Schedule A = Participants attended trial month visit 1, 4, 7, 10, 13 and 16/Exit 
Visit Schedule B = Participants attended trial month visit 1, 2, 5, 8, 11, 14 and 17/Exit 
Visit Schedule C = Participants attended trial month visit 1, 2, 3, 6, 9, 12 and 15/Exit 
 


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IPM 032 
 
Table 14.1.1.2 
Analysis Population Assignment 
Safety Population 
 
 
Page 5 of 93 
 
Version 1.0 
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Statistic 
Centre 01 
Centre 02 
… 
Centre 08 
All Centres 
 
 
 
 
 
 
 
Safety population 
N 
XXX 
XXX 
… 
XXX 
XXX 
m-ITT population 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
Virology population 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
PP population 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
m-ITT = Modified intent-to-treat; PP = Per-protocol  
a Percentages are calculated out of the participants in the safety population per centre 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07; Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 
 
 
 


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IPM 032 
 
 
 
Table 14.1.1.3 
Protocol Deviations 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 6 of 93 
 
Version 1.0 
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Statistic 
Centre 01 
(N=XXX) 
Centre 02 
(N=XXX) 
… 
Centre 08 
(N=XXX) 
All Centres 
(N=XXX) 
 
 
 
 
 
 
 
Participants with no reported protocol deviations 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
Participants with reported protocol deviations* 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Minor deviations 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Major deviations 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  No classification 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
Deviation criteria* 
 
 
 
 
 
 
  Inappropiate enrollment (failed to meet eligibility criteria) 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Missed visit 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Visit completed outside of permissible window 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Informed consent process deviations 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Investigational product deviations  
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Safety reporting deviations 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Failure to discontinueinvestigational product 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Inappropriate treatment/management of medical  
 
 
 
 
 
 
  conditions and follow-up of AEs 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Mishandled laboratory samples 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Missing or incorrectly timed trial procedures 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Conduct of additional non-trial related procedures 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Participant non-adherence to trial requirements 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Failure to discontinue participants who meet the trial  
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  discontinuation criteria 
 
 
 
 
 
 
  Other 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
Programmer’s Note: Please repeat this table for the following subgroups: Seroconverted prior to product use; Seroconverted on product use; Seroconverted after product 
use; No seroconversion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event 
Percentages are calculated out of the number of participants (per centre) a In the safety population b Reported a protocol deviation  
* More than one protocol deviation may have been reported for a participant; Where a subject reports more than one deviation per coded term they will only be counted  
once for the worst classification 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07; Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.1.2.1 
Demographics at Screening by IPM 027 Treatment Arm 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 7 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
 
All Centres 
Parameter (unit) 
Statistic 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
 (N=XXX) 
IPM 032  
Overall 
(N=XXX) 
… 
IPM 027  
Placebo 
 (N=XXX) 
IPM 032 
Overall 
(N=XXX) 
Age (years) 
n 
XXX 
XXX 
XXX 
 
XXX 
XXX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
 
Race 
 
 
 
 
 
 
 
  Coloured 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
X (  X.X) 
X (  X.X) 
  Black 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
X (  X.X) 
X (  X.X) 
  Indian 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
X (  X.X) 
X (  X.X) 
  Etc. 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Height (cm) 
n 
XXX 
XXX 
XXX 
 
XXX 
XXX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
 
Weight (kg) 
n 
XXX 
XXX 
XXX 
 
XXX 
XXX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
 
BMI (kg/m2) 
n 
XXX 
XXX 
XXX 
 
XXX 
XXX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
(XX, XX) 
(XX, XX) 
Programmer’s Note: Please repeat this table for the following subgroups: Seroconverted prior to product use; Seroconverted on product use; Seroconverted after product 
use; No seroconversion 
Percentages are calculated out of the number of participants (per centre and IPM 027 treatment) a In the safety population b With main partner 
Age = INT((Enrollment Date – Date of Birth)/365.25)); Body Mass Index (BMI) =  (body weight in kg)/(body height in m)2 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.1.2.1 
Demographics at Screening by IPM 027 Treatment Arm 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 8 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
 
All Centres 
Parameter (unit) 
Statistic 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
 (N=XXX) 
IPM 032  
Overall 
(N=XXX) 
… 
IPM 027  
Placebo 
(N=XXX) 
IPM 032  
Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
Education 
 
 
 
 
 
 
 
  Primary school 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Secondary school 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Tertiary education 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Marital status 
 
 
 
 
 
 
 
  Married 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Single 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Separated 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Divorced 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Widowed 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
With main partner 
 
 
 
 
 
 
 
  Yes 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  No 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Co-residential status w/ main  
 
 
 
 
 
 
 
Partner (past year) 
 
 
 
 
 
 
 
  Lived together all the time 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Lived together none of the time 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Lived together some of the time 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Current co-residential status w/ 
 
 
 
 
 
 
 
main partner 
 
 
 
 
 
 
 
  Yes 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  No 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmer’s Note: Please repeat this table for the following subgroups: Seroconverted prior to product use; Seroconverted on product use; Seroconverted after product 
use; No seroconversion 
Percentages are calculated out of the number of participants (per centre and IPM 027 treatment) a In the safety population b With main partner 
Age = INT((Enrollment Date – Date of Birth)/365.25)); Body Mass Index (BMI) =  (body weight in kg)/(body height in m)2 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.1.2.1 
Demographics at Screening by IPM 027 Treatment Arm 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 9 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
 
All Centres 
Parameter (unit) 
Statistic 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027  
Placebo 
 (N=XXX) 
IPM 032  
Overall 
(N=XXX) 
… 
IPM 027  
Placebo 
(N=XXX) 
IPM 032  
Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
Genital STIs at baseline 
 
 
 
 
 
 
 
  Yes 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  No 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Vaginal sex once a week or more 
 
 
 
 
 
 
 
in the past month 
 
 
 
 
 
 
 
  Yes 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  No 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Usual number of vaginal sex acts 
n 
XXX 
XXX 
XXX 
… 
XXX 
XXX 
 
Mean 
XX.X 
XX.X 
XX.X 
… 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
… 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
XX.XX 
… 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
… 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
 
No. of male sex partners at baseline 
 
 
 
 
 
 
 
  0-1 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  2 or more 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Partner knowledge of ring use 
 
 
 
 
 
 
 
  Yes 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  No 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Has children 
 
 
 
 
 
 
 
  Yes 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  No 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Programmer’s Note: Please repeat this table for the following subgroups: Seroconverted prior to product use; Seroconverted on product use; Seroconverted after product 
use; No seroconversion 
Percentages are calculated out of the number of participants (per centre and IPM 027 treatment) a In the safety population b With main partner 
Age = INT((Enrollment Date – Date of Birth)/365.25)); Body Mass Index (BMI) =  (body weight in kg)/(body height in m)2 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.1.2.2 
Demographics at Screening by Enrolled Status (from IPM 027) 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 10 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
 
All Centres 
Parameter (unit) 
Statistic 
Directly Enrolled 
In IPM 032 
 (N=XXX) 
Did Not Directly  
Enroll in IPM 032 
 (N=XXX) 
IPM 032 
Overall 
 (N=XXX) 
… 
Did Not Directly  
Enroll in IPM 032 
 (N=XXX) 
IPM 032 
Overall 
 (N=XXX) 
Age (years) 
n 
XXX 
XXX 
XXX 
… 
XXX 
XXX 
 
Mean 
XX.X 
XX.X 
XX.X 
… 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
… 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
XX.XX 
… 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
… 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
 
Race 
 
 
 
 
 
 
 
  Coloured 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Black 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Indian 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Etc. 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Height (cm) 
n 
XXX 
XXX 
XXX 
… 
XXX 
XXX 
 
Mean 
XX.X 
XX.X 
XX.X 
… 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
… 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
XX.XX 
… 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
… 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
 
Weight (kg) 
n 
XXX 
XXX 
XXX 
… 
XXX 
XXX 
 
Mean 
XX.X 
XX.X 
XX.X 
… 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
… 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
XX.XX 
… 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
… 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
 
BMI (kg/m2) 
n 
XXX 
XXX 
XXX 
… 
XXX 
XXX 
 
Mean 
XX.X 
XX.X 
XX.X 
… 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
… 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
XX.XX 
… 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
… 
(XX, XX) 
(XX, XX) 
Programmer’s Note: Please repeat this table for the following subgroups: Seroconverted prior to product use; Seroconverted on product use; Seroconverted after product 
use; No seroconversion 
Percentages are calculated out of the number of participants (per centre and enrolled status) a In the safety population b With main partner 
Age = INT((Enrollment Date – Date of Birth)/365.25)); Body Mass Index (BMI) =  (body weight in kg)/(body height in m)2 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.1.2.2 
Demographics at Screening by Enrolled Status (from IPM 027) 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 11 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
 
All Centres 
Parameter (unit) 
Statistic 
Directly Enrolled 
In IPM 032 
 (N=XXX) 
Did Not Directly  
Enroll in IPM 032 
 (N=XXX) 
IPM 032 
Overall 
 (N=XXX) 
… 
Did Not Directly  
Enroll in IPM 032 
 (N=XXX) 
IPM 032 
Overall 
 (N=XXX) 
 
 
 
 
 
 
 
 
Education 
 
 
 
 
 
 
 
  Primary school 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Secondary school 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Tertiary education 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Marital status 
 
 
 
 
 
 
 
  Married 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Single 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Separated 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Divorced 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Widowed 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
With main partner 
 
 
 
 
 
 
 
  Yes 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  No 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Co-residential status w/ main  
 
 
 
 
 
 
 
partner 
 
 
 
 
 
 
 
  Lived together all the time 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Lived together none of the time 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Lived together some of the time 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Current co-residential status w/ 
 
 
 
 
 
 
 
main partner 
 
 
 
 
 
 
 
  Yes 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  No 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmer’s Note: Please repeat this table for the following subgroups: Seroconverted prior to product use; Seroconverted on product use; Seroconverted after product 
use; No seroconversion 
Percentages are calculated out of the number of participants (per centre and enrolled status) a In the safety population b With main partner 
Age = INT((Enrollment Date – Date of Birth)/365.25)); Body Mass Index (BMI) =  (body weight in kg)/(body height in m)2 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.1.2.2 
Demographics at Screening by Enrolled Status (from IPM 027) 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 12 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
 
All Centres 
Parameter (unit) 
Statistic 
Directly Enrolled 
In IPM 032 
 (N=XXX) 
Did Not Directly  
Enroll in IPM 032 
 (N=XXX) 
IPM 032 
Overall 
 (N=XXX) 
… 
Did Not Directly  
Enroll in IPM 032 
 (N=XXX) 
IPM 032 
Overall 
 (N=XXX) 
 
 
 
 
 
 
 
 
Genital STIs at baseline 
 
 
 
 
 
 
 
  Yes 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  No 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Vaginal sex once a week or more 
 
 
 
 
 
 
 
in the past month 
 
 
 
 
 
 
 
  Yes 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  No 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Usual number of vaginal sex acts 
n 
XXX 
XXX 
XXX 
… 
XXX 
XXX 
 
Mean 
XX.X 
XX.X 
XX.X 
… 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
… 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
XX.XX 
… 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
… 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
 
No. of male sex partners 
 
 
 
 
 
 
 
  0-1 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  2 or more 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Partner knowledge of ring use 
 
 
 
 
 
 
 
  Yes 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  No 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
Has children 
 
 
 
 
 
 
 
  Yes 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  No 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmer’s Note: Please repeat this table for the following subgroups: Seroconverted prior to product use; Seroconverted on product use; Seroconverted after product 
use; No seroconversion 
Percentages are calculated out of the number of participants (per centre and enrolled status) a In the safety population b With main partner 
Age = INT((Enrollment Date – Date of Birth)/365.25)); Body Mass Index (BMI) =  (body weight in kg)/(body height in m)2 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.1.3.1 
Medical History at Screening 
Safety Population 
 
 
Page 13 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
Centre 01 
(N=XXX) 
Centre 02 
(N=XXX) 
… 
Centre 08 
(N=XXX) 
All Centres 
(N=XXX) 
 
 
 
 
 
 
 
Participants with no reported medical history 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
Participants with reported medical history* 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Percentages are calculated out of the number of participants in the safety population per centre 
* More than one diagnosis/condition may be reported by a participant  
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.1.3.2 
Contraceptive/ Menstrual/ Obstetric History at Screening 
Safety Population 
 
 
Page 14 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
Centre 01 
(N=XXX) 
Centre 02 
(N=XXX) 
… 
Centre 08 
(N=XXX) 
All Centres 
(N=XXX) 
 
 
 
 
 
 
 
Participants using any contraceptives* 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Oral contraceptive regimen 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Transdermal contraceptive patch 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Subcutaneous implant 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  IUD 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Surgical sterilisation 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Other 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
Menstrual bleeding 
 
 
 
 
 
 
  Regular cycle 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Irregular cycle 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Amenorrhoeic 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
Duration of menstrual cycle 
n 
XXX 
XXX 
… 
XXX 
XXX 
 
Mean 
XX.X 
XX.X 
… 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
… 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
… 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
… 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
Menstrual flow 
 
 
 
 
 
 
  Light 
n (%)c 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Moderate 
n (%)c 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Heavy 
n (%)c 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
IUD = Intrauterine device  
Percentages are calculated out of the number of participants (per centre) a In the safety population b Using contraceptives c Reported having menses d With a parity score > 0 
* More than one contraceptive may apply to a participant 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.1.3.2 
Contraceptive/ Menstrual/ Obstetric History at Screening 
Safety Population 
 
 
Page 15 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
Centre 01 
(N=XXX) 
Centre 02 
(N=XXX) 
… 
Centre 08 
(N=XXX) 
All Centres 
(N=XXX) 
 
 
 
 
 
 
 
History of dysmenorrhea  
 
 
 
 
 
 
  Yes 
n (%)c 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  No 
n (%)c 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
Gravidity 
 
 
 
 
 
 
  0 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  1-3 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  4+ 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
Parity  
 
 
 
 
 
 
  0 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  1-3 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  4+ 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
Vaginal deliveries 
 
 
 
 
 
 
  0 
n (%)d 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  1-3 
n (%)d 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  4+ 
n (%)d 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
Cesarean sections 
 
 
 
 
 
 
  0 
n (%)d 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  1-3 
n (%)d 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  4+ 
n (%)d 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
IUD = Intrauterine device  
Percentages are calculated out of the number of participants (per centre) a In the safety population b Using contraceptives c Reported having menses d With a parity score > 0 
* More than one contraceptive may apply to a participant 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.1.3.3 
Gynaecological History at Screening 
Safety Population 
 
 
Page 16 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
Centre 01 
(N=XXX) 
Centre 02 
(N=XXX) 
… 
Centre 08 
(N=XXX) 
All Centres 
(N=XXX) 
 
 
 
 
 
 
 
Participants with reported gynaecological history* 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
MedDRA System Organ Class 1 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  MedDRA Preferred Term 1 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  MedDRA Preferred Term 2 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please repeat for each system organ class and preferred term 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Percentages are calculated out of the number of participants (per centre) a In the safety population b With gynaecological data 
* More than one diagnosis/condition may be reported by a participant  
Gynaecological conditions were coded using MedDRA Version 19.0 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.1.3.4 
Prior Medication 
Safety Population 
 
 
Page 17 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
Centre 01 
(N=XXX) 
Centre 02 
(N=XXX) 
… 
Centre 08 
(N=XXX) 
All Centres 
(N=XXX) 
 
 
 
 
 
 
 
Partticipants with reported prior medication 
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
WHO Drug Name  
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Preferred name 1 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  Preferred name 2 
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please repeat for each drug name class and preferred term 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Percentages are calculated out of the number of participants (per centre) a In the safety population b Reported prior medication 
Prior medication is defined as any medication that started and ended before the first insertion of the investigational product (IP) 
Medications were coded using WHO DDE (version June 2017) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.1.1 
Overall Summary of Treatment Emergent Adverse Events 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 18 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
 
All Centres 
 
Statistic 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
… 
IPM 027 
Dapivirine 
 (N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
 
At least one TEAE 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
At least one serious TEAE 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
At least one DAIDS Grade 3 or 4 TEAE 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
At least one product-related TEAE 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
At least one serious product-related TEAE 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
TEAEs leading to death 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
TEAEs leading to permanent IP discontinuation 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
TEAEs leading to temporary IP discontinuation 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
TEAEs leading to trial discontinuation 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Urogenital TEAEs 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Social harms reported as TEAEs 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Non TEAEs 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please repeat table for the following subgroup: IPM 027 participants who directly enrolled in IPM 032 (Note that the number of participants in the headers 
(N=XXX) should reflect the number of participants in each subgroup) 
 
 
 
 
 
 
 
 
 
IP = Investigational product; TEAE = Treatment emergent adverse event 
Deaths are not included in summary 
a Percentages are calculated out of the number of participants in the safety population per centre and IPM 027 treatment  
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.1.2 
Treatment Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Population 
Subgroup: All IPM 032 participants  
 
Page 19 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
… 
All Centres 
MedDRA System Organ Class 
  MedDRA Preferred Term 
Statistic 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
 (N=XXX) 
… 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
 (N=XXX) 
 
 
 
 
 
 
 
 
 
Any TEAE 
n (%)a  
X (  X.X)  
X (  X.X)  
X (  X.X) 
… 
X (  X.X)  
X (  X.X)  
X (  X.X)  
 
95% CIb 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
 
MedDRA System Organ Class 1 
n (%)a  
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  MedDRA Preferred Term 1 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  MedDRA Preferred Term 2 
n (%)a  
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- Please repeat for each primary system organ class and preferred term 
- Please repeat table for the following subgroup: IPM 027 participants who directly enrolled in IPM 032 (Note that the number of participants in the headers (N=XXX) should 
reflect the number of participants in each subgroup) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CI = Confidence interval; TEAE = Treatment emergent adverse event 
a Percentages are calculated out of the number of participants in the safety population per centre and IPM 027 treatment 
b 95% CI are calculated using Fisher’s exact test 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.1.3 
Product-Related Treatment Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 20 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
… 
All Centres 
MedDRA System Organ Class 
  MedDRA Preferred Term 
Statistic 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
… 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
 
Any IP related TEAE 
n (%)a  
X (  X.X)  
X (  X.X)  
X (  X.X) 
… 
X (  X.X)  
X (  X.X)  
X (  X.X)  
 
95% CIb 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
 
MedDRA System Organ Class 1 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  MedDRA Preferred Term 1 
n (%)a  
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  MedDRA Preferred Term 2 
n (%)a  
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- Please repeat for each primary system organ class and preferred term 
- Please repeat table for the following Subgroups: Age < 25 years; Age ≥ 25 years and IPM 027 participants who directly enrolled in IPM 032 (Note that the number of 
participants in the headers (N=XXX) should reflect the number of participants in each subgroup) 
 
 
 
 
 
 
 
 
 
CI = Confidence interval; IP = Investigational product; TEAE = Treatment emergent adverse event 
a Percentages are calculated out of the number of participants in the safety population per centre and IPM 027 treatment 
b 95% CI are calculated using Fisher’s exact test 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.1.4 
Grade 3 or 4 Treatment Emergent Adverse Events by System Organ Class and Preferred Term 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 21 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
… 
All Centres 
MedDRA System Organ Class 
  MedDRA Preferred Term 
Statistic 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
… 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
 
Any Grade 3 or Grade 4 TEAE 
n (%)a  
X (  X.X)  
X (  X.X)  
X (  X.X) 
… 
X (  X.X)  
X (  X.X)  
X (  X.X)  
 
95% CIb 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
 
MedDRA System Organ Class 1 
n (%)a  
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  MedDRA Preferred Term 1 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  MedDRA Preferred Term 2 
n (%)a  
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- Please repeat for each primary system organ class and preferred term 
- Please repeat table for the following Subgroups: Age < 25 years; Age ≥ 25 years (Note that the number of participants in the headers (N=XXX) should 
reflect the number of participants in each subgroup) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CI = Confidence interval; TEAE = Treatment emergent adverse event 
a Percentages are calculated out of the number of participants in the safety population per centre and IPM 027 treatment 
b 95% CI are calculated using Fisher’s exact test 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.1.5 
Serious Treatment Emergent Adverse Events by Primary System Organ Class and Preferred Term 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 22 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
 
All Centres 
MedDRA System Organ Class 
  MedDRA Preferred Term 
Statistic 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
… 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
 
Any serious TEAE 
n (%)a  
X (  X.X)  
X (  X.X)  
X (  X.X) 
… 
X (  X.X)  
X (  X.X)  
X (  X.X)  
 
95% CIb 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
… 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
 
MedDRA System Organ Class 1 
n (%)a  
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  MedDRA Preferred Term 1 
n (%)a  
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  MedDRA Preferred Term 2 
n (%)a  
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- Please repeat for each primary system organ class and preferred term 
- Please repeat table for the following Subgroups: Age < 25 years; Age ≥ 25 years and IPM 027 participants who directly enrolled in IPM 032 (Note that the number of 
participants in the headers (N=XXX) should reflect the number of participants in each subgroup) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CI = Confidence interval; TEAE = Treatment emergent adverse event 
a Percentages are calculated out of the number of participants in the safety population per centre and IPM 027 treatment 
b 95% CI are calculated using Fisher’s exact test 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.1.6 
Urogenital Treatment Emergent Adverse Events by Primary System Organ Class and Preferred Term 
Safety Population 
 
 
Page 23 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
 
All Centres 
MedDRA System Organ Class 
  MedDRA Preferred Term 
Statistic 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
… 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
 
Any urogenital TEAE 
n (%)a  
X (  X.X)  
X (  X.X)  
X (  X.X) 
… 
X (  X.X)  
X (  X.X)  
X (  X.X)  
 
95% CIb 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
… 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
 
MedDRA System Organ Class 1 
n (%)a  
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  MedDRA Preferred Term 1 
n (%)a  
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  MedDRA Preferred Term 2 
n (%)a  
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please repeat for each primary system organ class and preferred term 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TEAE = Treatment emergent adverse event 
a Percentages are calculated out of the number of participants in the safety population per centre and IPM 027 treatment 
b 95% CI are calculated using Fisher’s exact test 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.1.7 
Treatment Emergent Adverse Events by Worst Severity, Primary System Organ Class and Preferred Term 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 24 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 01 
… 
All Centres 
MedDRA System Organ Class 
  MedDRA Preferred Term 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
… 
IPM 027 Dapivirine 
(N=XXX) 
… 
IPM 032 Overall 
(N=XXX) 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
… 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
… 
Grade 1 
n (%)a 
… 
Grade 5 
n (%)a 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MedDRA System Organ Class 1 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
  MedDRA Preferred Term 1 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
  MedDRA Preferred Term 2 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- Please repeat for each primary system organ class and preferred term 
- Please repeat the table for the following subgroup: IPM 027 participants who directly enrolled in IPM 032 (Note that the number of participants in the headers (N=XXX) 
should reflect the number of participants in each subgroup) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Percentages are calculated out of the number of participants in the safety population per centre and IPM 027 treatment 
Severity Grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death 
Where a subject reports more than one adverse event per SOC and preferred term they will only be counted once for the worst severity 
A missing severity grade is assumed to be 4 
System organ class and preferred term were coded using MedDRA (Version 19.0). 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.1.8 
Serious Treatment Emergent Adverse Events by Worst Severity, Primary System Organ Class and Preferred Term 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 25 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 01 
… 
All Centres 
MedDRA System Organ Class 
  MedDRA Preferred Term 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
… 
IPM 027 Dapivirine 
(N=XXX) 
… 
IPM 032 Overall 
(N=XXX) 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
… 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
… 
Grade 1 
n (%)a 
… 
Grade 5 
n (%)a 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MedDRA System Organ Class 1 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
  MedDRA Preferred Term 1 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
  MedDRA Preferred Term 2 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- Please repeat for each primary system organ class and preferred term 
- Please repeat the table for the following subgroup: IPM 027 participants who directly enrolled in IPM 032 (Note that the number of participants in the headers (N=XXX) 
should reflect the number of participants in each subgroup) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Percentages are calculated out of the number of participants in the safety population per centre and IPM 027 treatment 
Severity Grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death 
Where a subject reports more than one adverse event per SOC and preferred term they will only be counted once for the worst severity 
A missing severity grade is assumed to be 4 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.1.9 
Product-Related Treatment Emergent Adverse Events by Worst Severity, Primary System Organ Class and Preferred Term 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 26 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 01 
… 
All Centres 
MedDRA System Organ Class 
  MedDRA Preferred Term 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
… 
IPM 027 Dapivirine 
(N=XXX) 
… 
IPM 032 Overall 
(N=XXX) 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
… 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
… 
Grade 1 
n (%)a 
… 
Grade 5 
n (%)a 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MedDRA System Organ Class 1 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
  MedDRA Preferred Term 1 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
  MedDRA Preferred Term 2 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- Please repeat for each primary system organ class and preferred term 
- Please repeat the table for the following subgroup: IPM 027 participants who directly enrolled in IPM 032 (Note that the number of participants in the headers (N=XXX) 
should reflect the number of participants in each subgroup) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Percentages are calculated out of the number of participants in the safety population per centre and IPM 027 treatment 
Severity Grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death 
Where a subject reports more than one adverse event per SOC and preferred term they will only be counted once for the worst severity 
A missing severity grade is assumed to be 4 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.1.10 
Serious Product-Related Treatment Emergent Adverse Events by Worst Severity, Primary System Organ Class and Preferred Term 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 27 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 01 
… 
All Centres 
MedDRA System Organ Class 
  MedDRA Preferred Term 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
… 
IPM 027 Dapivirine 
(N=XXX) 
… 
IPM 032 Overall 
(N=XXX) 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
… 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
… 
Grade 1 
n (%)a 
… 
Grade 5 
n (%)a 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MedDRA System Organ Class 1 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
  MedDRA Preferred Term 1 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
  MedDRA Preferred Term 2 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- Please repeat for each primary system organ class and preferred term 
- Please repeat the table for the following subgroup: IPM 027 participants who directly enrolled in IPM 032 (Note that the number of participants in the headers (N=XXX) 
should reflect the number of participants in each subgroup) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Percentages are calculated out of the number of participants in the safety population per centre and IPM 027 treatment 
Severity Grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death 
Where a subject reports more than one adverse event per SOC and preferred term they will only be counted once for the worst severity 
A missing severity grade is assumed to be 4 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.1.11 
Social Harms Reported as Treatment Emergent Adverse Events by Worst Severity, Primary System Organ Class and Preferred Term 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 28 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 01 
… 
All Centres 
MedDRA System Organ Class 
  MedDRA Preferred Term 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
… 
IPM 027 Dapivirine 
(N=XXX) 
… 
IPM 032 Overall 
(N=XXX) 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
… 
Grade 1 
n (%)a 
…
Grade 5 
n (%)a 
… 
Grade 1 
n (%)a 
… 
Grade 5 
n (%)a 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MedDRA System Organ Class 1 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
  MedDRA Preferred Term 1 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
  MedDRA Preferred Term 2 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
… X (  X.X) 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- Please repeat for each primary system organ class and preferred term 
- Please repeat the table for the following subgroup: IPM 027 participants who directly enrolled in IPM 032 (Note that the number of participants in the headers (N=XXX) 
should reflect the number of participants in each subgroup) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Percentages are calculated out of the number of participants in the safety population per centre and IPM 027 treatment 
Severity Grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death 
Where a subject reports more than one adverse event per SOC and preferred term they will only be counted once for the worst severity 
A missing severity grade is assumed to be 4 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.5.1 
Adherence, Overall Summary of Dapivirine Residual Levels (mg) in Used Rings 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 29 of 93 
 
Version 1.0 
26 Mar 2020 
 
Month Ring Used 
Trial 
n 
Mean 
Q1 
Median 
Q3 
SD 
Min 
Max 
95% CIb 
 
 
 
 
 
 
 
 
 
 
 
Enrolment / 
IPM 032 / 
XXX 
XX.X 
XX.X 
XX.X 
XX.X 
XX.XX 
XX 
XX 
XX.X, XX.X 
Trial Month X 
IPM 027 
XXX 
XX.X 
XX.X 
XX.X 
XX.X 
XX.XX 
XX 
XX 
XX.X, XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please repeat table for the following Subgroups: Martital status: Married; Martital status:  Unmarried; Age < 25 years; Age ≥ 25 years; Main sex partner: 
Yes; Main sex partner: No; Presence of genital symptoms/STIs: Yes; Presence of genital symptoms/STIs: No (Note that the number of participants (n) should reflect the 
number of participants in each subgroup) 
 
 
 
 
 
 
 
 
 
 
 
CI = Confidence interval 
b 95% CI for the mean 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NC


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.5.2 
Adherence, Summary of Dapivirine Residual Levels (mg) in Used Rings by Category 
Safety Population 
 
 
Page 30 of 93 
 
Version 1.0 
26 Mar 2020 
 
Month Ring Used 
Trial 
All Rings  
0 - < 20 mg 
n (%)a 
20 - ≤ 21 mg 
n (%)a 
> 21 - ≤ 22 mg 
n (%)a 
> 22 - ≤ 23.5 mg 
n (%)a 
> 23.5 mg 
n (%)a 
 
 
 
 
 
 
 
 
Enrolment / 
IPM 032 / 
XXX 
X ( X.X) 
X ( X.X) 
X ( X.X) 
X ( X.X) 
X ( X.X) 
Trial Month X 
IPM 027 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Percentages are calculated out of the total number of rings per trial month  
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.5.3 
Adherence, Summary Relating Ring Residual Levels (mg) to Time Intervals Between Consecutive Ring Replacements 
Safety Population 
 
 
Page 31 of 93 
 
Version 1.0 
26 Mar 2020 
 
Month Ring Used 
Time Interval Between Consecutive Ring Replacements 
for Residual Levels in Ring 
n 
Mean 
Q1 
Median 
Q3 
SD 
Min 
Max 
 
 
 
 
 
 
 
 
 
 
Enrolment / 
< 23 days 
XXX 
XX.X 
XX.X 
XX.X 
XX.X 
XX.XX 
XX 
XX 
Trial Month X 
23 – 37 days 
XXX 
XX.X 
XX.X 
XX.X 
XX.X 
XX.XX 
XX 
XX 
 
> 37 – 84 days 
XXX 
XX.X 
XX.X 
XX.X 
XX.X 
XX.XX 
XX 
XX 
 
> 84 days 
XXX 
XX.X 
XX.X 
XX.X 
XX.X 
XX.XX 
XX 
XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.5.4 
Residual Levels of Dapivirine (mg) in the Last Three Rings Returned by Participants Who Seroconverted, Prior to HIV-1 Seroconversion 
Safety Population 
 
 
Page 32 of 93 
 
Version 1.0 
26 Mar 2020 
 
Appearance 
  Colour 
Statistic 
HIV + 
(N=XXX) 
HIV – 
(N=XXX) 
 
 
 
 
Used 
 
 
 
  White to off-white 
n, r 
XXX, XXX 
XXX, XXX 
 
Mean 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
 
 
 
 
  Slight yellow to yellow 
n, r 
XXX, XXX 
XXX, XXX 
 
Mean 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
 
 
 
 
  Tan 
n, r 
XXX, XXX 
XXX, XXX 
 
Mean 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
 
 
 
 
  Brown 
n, r 
XXX, XXX 
XXX, XXX 
 
Mean 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
 
 
 
 
  Other 
n, r 
XXX, XXX 
XXX, XXX 
 
Mean 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
Programmers Note:  Please repeat for the following appearance categories: Unused; Not sure  
 
 
 
 
n = Number of participants; r = Number of rings 
HIV-1 = Human immunodeficiency virus type 1; HIV+ = Participants who HIV-1 seroconverted during trial duration; HIV- = Participants who remained HIV- for the duration of the trial 
Only the residual levels of dapivirine in the last three rings returned by participants who HIV-1 seroconverted, prior to HIV-1 seroconversion, are included. All residual levels are used for 
participants that remained HIV- for the duration of the trial.


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.5.5 
Self-Reported Adherence to Dapivirine Ring 
Safety Population 
 
 
Page 33 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
 
All Centres 
Month Ring Used 
Analysis Category 
IPM 027 
Dapivirine 
n (%)a 
IPM 027 
Placebo 
n (%)a 
IPM 032 
Overall 
n (%)a 
… 
IPM 027 
Dapivirine 
n (%)a 
IPM 027 
Placebo 
n (%)a 
IPM 032 
Overall 
n (%)a 
 
 
 
 
 
 
 
 
 
Trial month X / 
n 
XXX 
XXX 
XXX 
… 
XXX 
XXX 
XXX 
Exit visit 
< 80% 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
≥ 80% - < 90% 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
≥ 90% 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Percentages are calculated out of the number of participants in the safety population per centre and IPM 027 treatment with available data 
Adherence rate per was calculated as 100 x (number of days that the participant reportedly wore the ring/the total number of days that the participant was expected to wear the ring) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.5.6 
Self-Reported Acceptability of Dapivirine Ring 
Safety Population 
 
 
Page 34 of 93 
 
Version 1.0 
26 Mar 2020 
 
LPUV Question 
Statistic 
IPM 032 Overall 
(N=XXX) 
 
 
 
Participants who responded positively to the following 
 
 
  Do you think it is possible for women to use the ring as requested (i.e. without removing it)?  
n (%)a 
X (  X.X) 
 
95% CIb 
XX, XX 
 
 
 
  Do you think women in your community would want to use this ring if it were available? 
n (%)a 
X (  X.X) 
 
95% CIb 
XX, XX 
 
 
 
CI = Confidence interval; LPUV = Last product use visit 
a Percentages are calculated out of the number of participants in the safety population  
b 95% CI calculated using Fisher’s exact test 
A participant will be classified as having found the vaginal ring acceptable if she responds positively to the first question, about keeping the ring inserted as prescribed. Community 
acceptability will be demonstrated by positive responses to the second question 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.5.7 
Accidental Ring Expulsion/ Removal 
Safety Population 
 
 
Page 35 of 93 
 
Version 1.0 
26 Mar 2020 
 
Visit 
Reason Ring Was Removed / Came Out 
Statistic 
IPM 032 Overall 
(N=XXX) 
 
 
 
 
Trial Month X 
Participants who had an accidental ring removal/expulsion 
n (%)a 
X (  X.X) 
 
Participants who had no accidental ring removals/expulsions 
n (%)a 
X (  X.X) 
 
… 
 
 
 
 
 
 
 
 
 
 
a Percentages are calculated out of the number of participants in the safety population 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.6.1 
Vital Signs 
Safety Population 
 
 
Page 36 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
 
All Centres 
Parameter (unit) 
   Visit 
Statistic 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
… 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
 
Parameter (unit) 
 
 
 
 
 
 
 
 
  Baseline  
n 
XXX 
XXX 
XXX 
… 
XXX 
XXX 
XXX 
 
Mean 
XX.X 
XX.X 
XX.X 
… 
XX.X 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,X
X.X) 
(XX.X,XX.X,X
X.X) 
(XX.X,XX.X,X
X.X) 
… 
(XX.X,XX.X,X
X.X) 
(XX.X,XX.X,X
X.X) 
(XX.X,XX.X,X
X.X) 
 
SD 
XX.XX 
XX.XX 
XX.XX 
… 
XX.XX 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
… 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
… 
 
 
 
  LPUV 
n 
XXX 
XXX 
XXX 
… 
XXX 
XXX 
XXX 
 
Mean 
XX.X 
XX.X 
XX.X 
… 
XX.X 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,X
X.X) 
(XX.X,XX.X,X
X.X) 
(XX.X,XX.X,X
X.X) 
… 
(XX.X,XX.X,X
X.X) 
(XX.X,XX.X,X
X.X) 
(XX.X,XX.X,X
X.X) 
 
SD 
XX.XX 
XX.XX 
XX.XX 
… 
XX.XX 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
… 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
… 
 
 
 
  Change from baseline to  
n 
XXX 
XXX 
XXX 
… 
XXX 
XXX 
XXX 
  LPUV 
Mean 
XX.X 
XX.X 
XX.X 
… 
XX.X 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,X
X.X) 
(XX.X,XX.X,X
X.X) 
(XX.X,XX.X,X
X.X) 
… 
(XX.X,XX.X,X
X.X) 
(XX.X,XX.X,X
X.X) 
(XX.X,XX.X,X
X.X) 
 
SD 
XX.XX 
XX.XX 
XX.XX 
… 
XX.XX 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
… 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
95% CIa 
XX, XX 
XX, XX 
XX, XX 
 
XX, XX 
XX, XX 
XX, XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- Please repeat for each measured parameter 
- 95% CIs are calculated for Change from Baseline only 
 
 
 
 
 
 
 
 
 
CI = Confidence interval; LPUV = Last product use visit 
a 95% CI for the mean 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.1 
Pelvic/ Speculum Examinations 
Safety Population 
 
 
Page 37 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
Centre 01 
 
All Centres 
Visit 
Findings  
  Indicator 
Statistic 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
… 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032  
Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
 
 
Trial Month X 
 Presence of vulvar findings 
N 
XXX 
XXX 
XXX 
… 
XXX 
XXX 
XXX 
 
   Vulvar erythema 
 
 
 
 
 
 
 
 
 
   Vulvar edema 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
   Vulvar rash 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
   Etc. 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- Please repeat for the presence of Cervical findings, General/other findings, Vulvar Lesions findings, Vaginal Lesions findings, Cervical Lesions findings, and Cervical ectop 
- Please repeat table for all available visits 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LPUV = Last product use visit 
a Percentages are calculated out of the number of participants in the safety population per centre and IPM 027 treatment 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.2 
Cervical Cytology at Baseline 
Safety Population 
 
 
Page 38 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
… 
All Centres 
Findings  
Statistic 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
 
Negative for intraepithelial lesion or cancer 
 
 
 
 
 
 
 
 
(malignancy) 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
ASCUS 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
SIL-low grade  
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
ASC-H 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
SIL-high grade 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
AGC 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
AGC-favor neoplastic 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Cancer 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Other findings 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Percentages are calculated out of the number of participants in the safety population per centre and IPM 027 treatment 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.3 
Sexually Transmitted Infections 
Safety Population 
 
 
Page 39 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
 
All Centres 
Visit 
  Test 
Statistic 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
 
… 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
 
Screening 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Any STI* 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Chlamydia positive 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Syphilis RPR 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Gonorrhoea positive 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Trichomonas positive 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Blood present during collection  
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  of cervico-vaginal samples 
n (%)a 
 
 
 
… 
 
 
 
 
 
 
 
 
… 
 
 
 
LPUV 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Any STI* 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Chlamydia positive 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Syphilis confirmatory test  
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  TPHA/TPPA 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Gonorrhoea positive 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Trichomonas positive 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Blood present during collection  
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  of cervico-vaginal samples 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LPUV = Last product use visit 
a Percentages are calculated out of the number of participants in the safety population per centre and IPM 027 treatment 
* Includes Chlamydia, Gonorrhoea, Syphilis and Trichomonas 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.4 
Immediately Reportable Events 
Safety Population 
 
 
Page 40 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Centre 01 
 
All Centres 
Event 
Statistic 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
… 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
(N=XXX) 
Number of participants confirmed pregnant 
 
 
 
 
 
 
 
 
  Number op participants confirmed pregnant 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Total number of person-years 
PY 
XXX 
XXX 
XXX 
… 
XXX 
XXX 
XXX 
  Pregnancy incidence rate (per 100 person-years) 
 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
  Number of confirmed pregnancies 
n 
XXX 
XXX 
XXX 
… 
XXX 
XXX 
XXX 
 
 
 
 
 
 
 
 
 
Pregnancy report 
 
 
 
 
 
 
 
 
  Number of confirmed pregnancies 
n 
XXX 
XXX 
XXX 
… 
XXX 
XXX 
XXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Contraceptive method at the time of positive  
pregnancy test 
 
 
 
 
 
 
 
 
  Oral contraceptive 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Transdermal contraceptive patch 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Long acting injectable progestins 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy outcome 
 
 
 
 
 
 
 
 
  Full term live birth (≥ 37 weeks) 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Premature term live birth (< 37 weeks) 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Stillbirth/intrauterine fetal demise (≥ 20 weeks) 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV-1 Seroconverters 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1 
PY = (Date of last ring removal – Date of first ring insertion + 1)/365.25 
Percentages are calculated out of the number of participants (per centre and IPM 027 treatment) a In the safety population b Total pregnancy outcomes  
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.5 
Analysis 1, HIV-1 Seroconversion Rate per 100 Person-Years of Product Use 
Population: m-ITT 
 
Page 41 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
 
 
 
 
 
Number of confirmed HIV-1 seroconversions on IP 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Total number of person-years 
PY 
XXX 
XXX 
XXX 
Seroconversion rate (per 100 person-years) 
n/PY 
XX.X 
XX.X 
XX.X 
95% CI for seroconversion-rate (per 100 person-years) 
95% CIb 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
Programmers Note: Please repeat the table for the PP population 
 
 
 
 
 
CI = Confidence interval; HIV-1 = Human immunodeficiency virus type 1; IP = Investigational product 
a Percentages are calculated out of the number of participants in the applicable population per IPM 027 treatment 
b 95% CI calculated as [ (n/PY) ± 1.96 x ( [n/PY] / PY )½ ] x 100; where n = number of HIV seroconversions and PY = total number of person-years of product use 
calculated as PY = (Date of last ring removal – Date of first ring insertion + 1)/365.25 
 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.6 
Analysis 2, HIV-1 Seroconversion Rate per 100 Person-Years of Product Use 
m-ITT 
 
 
Page 42 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
 
 
 
 
 
Number of confirmed HIV-1 seroconversions on IP 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Total number of person-years 
PY 
XXX 
XXX 
XXX 
Seroconversion rate (per 100 person-years) 
n/PY 
XX.X 
XX.X 
XX.X 
95% CI for seroconversion-rate (per 100 person-years) 
95% CIb 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
 
 
CI = Confidence interval; HIV-1 = Human immunodeficiency virus type 1; IP = Investigational product 
a Percentages are calculated out of the number of participants in the m-ITT population per IPM 027 treatment 
b 95% CI calculated as [ (n/PY) ± 1.96 x ( [n/PY] / PY )½ ] x 100; where n = number of HIV seroconversions and PY = total number of person-years of product use 
calculated as PY = (Date of last ring removal – Date of first ring insertion + 1)/365.25 
In instances where it cannot be ruled out that HIV-1 infection may have occurred during IP use in case the HIV RNA test has detectable levels at the next visit after ring use, such 
participants will be considered as being seroconverted 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.7 
Analysis 3, HIV-1 Seroconversion Rate per 100 Person-Years of Product Use 
m-ITT 
 
 
Page 43 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
 
 
 
 
 
Number of confirmed HIV-1 seroconversions on IP 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Total number of person-years 
PY 
XXX 
XXX 
XXX 
Seroconversion rate (per 100 person-years) 
n/PY 
XX.X 
XX.X 
XX.X 
95% CI for seroconversion-rate (per 100 person-years) 
95% CIb 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
 
 
 
CI = Confidence interval; HIV-1 = Human immunodeficiency virus type 1; IP = Investigational product 
a Percentages are calculated out of the number of participants in the m-ITT population per IPM 027 treatment 
b 95% CI calculated as [ (n/PY) ± 1.96 x ( [n/PY] / PY )½ ] x 100; where n = number of HIV-1 seroconversions and PY = total number of person-years of product use 
calculated as PY = (Date of last ring removal – Date of first ring insertion + 1)/365.25 
All confirmed HIV-1 seroconverters determined to have been HIV-1 infected after enrollment will be considered as infected on product, even instances where HIV-1 seroconversion  
and estimated point of infection was determined to be after the last product use visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.8 
Analysis 4, HIV-1 Infection Rate per 100 Person-Years of Product Use 
m-ITT Population 
 
 
Page 44 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
 
 
 
 
 
Number of confirmed HIV-1 infections on IP 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Total number of person-years 
PY 
XXX 
XXX 
XXX 
Infection rate (per 100 person-years) 
n/PY 
XX.X 
XX.X 
XX.X 
95% CI for infection-rate (per 100 person-years) 
95% CIb 
(XX.X, XX.X) 
(XX.X, XX.X) 
(XX.X, XX.X) 
 
 
 
 
 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1; IP = Investigational product 
a Percentages are calculated out of the number of participants in the m-ITT population per IPM 027 treatment 
b 95% CI calculated as [ (n/PY) ± 1.96 x ( [n/PY] / PY )½ ] x 100; where n = number of HIV-1 infections and PY = total number of person-years of product use 
calculated as PY = (Date of last ring removal – Date of first ring insertion + 1)/365.25 
Similar to Analysis 1, but based on time to first positive HIV-1 RNA


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.9 
Overview of Number of Participants in the Trial 
Safety Population 
 
 
Page 45 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
 
 
 
 
 
Participants in the safety population 
N 
XXX 
XXX 
XXX 
Participants in the m-ITT population 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Participants in the virology population 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Participants without HIV-1 seroconversion 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Participants with HIV-1 seroconversion 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Participants with HIV-1 seroconversion prior to IP 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Participants with HIV-1 seroconversion on IP 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Participants with HIV-1 seroconversion after IP (LPUV) 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Participants with HIV-1 seroconversion – not prior/on/after IP 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1;IP = Investigational product; LPUV = Last product use visit 
a Percentages are calculated out of the number of participants in the safety population per IPM 027 treatment 
Seroconversion prior to IP: Participant was already HIV-infected at Enrollment before commencing Dapivirine Vaginal Ring-004 use, based on reverse sequential HIV RNA PCR testing; 
Seroconversion on IP: HIV seroconverted participant was determined to have been HIV-1 infected while on IP, as evaluated by the Principal Investigator/designee once the HIV-1 point of 
infection had been estimated based on reverse sequential HIV RNA PCR testing; 
Seroconversion after IP: Participant became HIV-1 infected after the Last Product Use Visit; 
Seroconversion – not prior/on/after IP: One participant discontinued ring use for 5 months (as she was not planning on continuing in the trial) before seroconverting, and one had a 
plasma HIV-1 ribonucleic acid (RNA) concentration below the limit of detection at the Last Product Use Visit (and a re-test of the same sample was negative)


 
 
Table 14.3.7.10.2 
Reverse Transcriptase Inhibitor and Protease Inhibitor Resistance-Associated Mutations Observed at Any Timepoint 
Virology Population 
Subgroup: All IPM 032 participants 
 
Page 46 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
 
 
 
 
 
Participants who HIV-1 seroconverted on IP  
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Participants who had a resistance test performed  
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Participants with a successful resistance test result 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Participants with HIV-1 drug resistance-associated mutations 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
NNRTI mutationsc 
 
 
 
 
   A98G 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
   E138A 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
   … 
… 
… 
… 
… 
NRTI mutationsc 
 
 
 
 
  E44D 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  … 
… 
… 
… 
… 
Major PI mutationsc 
 
 
 
 
  L33F 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  M46L 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  … 
… 
… 
… 
… 
 
Programmers Notes:  
- 
Please repeat table for the following subgroups: HIV-1 RNA level: HIV-1 RNA level: ≥ 2000 copies/mL, < 2000 copies/mL); HIV-1 subtype (C / Other); Schedule A, 
B or C 
- 
Table 14.7.10.2 will be similar to Table 14.7.10.1 but the heading and analysis will be based on Any Timepoint 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1; NNRTI = Non-nucleoside reverse transcriptase inhibitor ; NRTI = Nucleoside reverse transcriptase inhibitor; PI = Protease inhibitor 
Percentages are calculated out of the number of participants (per IPM 027 treatment) a In the virology population b Successful results 
c Resistance-associated mutations of interest not present in the data set are not included in the table 
Resistance-associated mutations were defined using the Stanford HIV database algorithm Version 8. 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.11 
Data Overview of HIV-1 Seroconversion Timing Relative To HIV-1 RNA Detection and Treatment 
Virology Population 
 
 
Page 47 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
 
 
 
 
 
First positive HIV-1 RNA Timing 
 
 
 
 
  At time of seroconversion  
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Mutations detected before seroconversion 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Mutations detected at seroconversion 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Mutations detected after seroconversion 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Before seroconversion 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Mutations detected before seroconversion 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Mutations detected at seroconversion 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Mutations detected after seroconversion 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Average days 
Mean 
XX.X 
XX.X 
XX.X 
    Minimum and maximum days 
(Min,Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
IP use stopped 
 
 
 
 
  At time of seroconversion 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  After seroconversion 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Before seroconversion 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
Programmers Note: In case the date of last investigational product exposure (i.e. last ring removal) is missing, it is imputed with the last ring insertion date. 
 
 
 
 
 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1 
Percentages are calculated out of the number of participants (per IPM 027 treatment) a In the virology population b At the applicable visit 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.12 
Overview of HIV-1 RNA and Genotyping Information Availability 
Virology Population 
 
 
Page 48 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
 
 
 
 
 
HIV-1 RNA for participants with HIV-1 seroconversion 
 
 
 
 
  Participants with assessment prior to seroconversion 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    No HIV-1 RNA detected in any sample 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    HIV-1 RNA detected in at least 1 sample 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Participants with assessment at time of seroconversion 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Participants with assessment after seroconversion (on IP) 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Participants with assessment after seroconversion (after IP) 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Participants without assessment at time of seroconversion 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
Population-based sequencing 
 
 
 
 
  Participants with assessment prior to seroconversion 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Plasma HIV-1 RNA ≥2000 cop/mL 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Plasma HIV-1 RNA <2000 cop/mL, ≥200 cop/mL 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Participants with assessment at time of seroconversion 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Plasma HIV-1 RNA ≥2000 cop/mL 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Plasma HIV-1 RNA <2000 cop/mL, ≥200 cop/mL 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Participants with assessment after seroconversion (on IP) 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Plasma HIV-1 RNA ≥2000 cop/mL 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Plasma HIV-1 RNA <2000 cop/mL, ≥200 cop/mL 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Participants with assessment after seroconversion (after IP) 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Plasma HIV-1 RNA ≥2000 cop/mL 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Plasma HIV-1 RNA <2000 cop/mL, ≥200 cop/mL 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1 
Percentages are calculated out of the number of participants (per IPM 027 treatment) a  In the virology population b With data c With a population-based sequencing assessment 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.12 
Overview of HIV-1 RNA and Genotyping Information Availability 
Virology Population 
 
 
Page 49 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
 
 
 
 
 
Population-based sequencing 
 
 
 
 
  Participants without assessment at time of seroconversion 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
HIV-1 Subtype 
 
 
 
 
  A1 
n (%)c 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  C 
n (%)c 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Etc. 
n (%)c 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1 
Percentages are calculated out of the number of the number of participants (per IPM 027 treatment)  a  In the virology population  b With c  With a population-based sequencing assessment 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.13.1 
Summary of Mutational Patterns of Resistance-Associated Mutations at Seroconversion Timepoint 
Virology Population 
Subgroup: All IPM 032 participants 
 
Page 50 of 93 
 
Version 1.0 
26 Mar 2020 
 
Resistance-Associated Mutation Combination 
Statistic 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
 
 
 
 
 
Number of successful assessments 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
NNRTI mutations 
 
 
 
 
   None 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
   Any 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
     One 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
     Two 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
     Three 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  … 
… 
… 
… 
… 
  Average 
Mean 
XX.X 
XX.X 
XX.X 
NRTI mutations 
 
 
 
 
   None 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
   Any 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
     One 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
     Two 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
     Three 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  … 
… 
… 
… 
… 
  Average 
Mean 
XX.X 
XX.X 
XX.X 
Major PI mutations 
 
 
 
 
   None 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
   Any 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
     One 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
     Two 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
     Three 
n (%)b 
X (  X.X) 
X (  X.X) 
X (  X.X) 
   … 
… 
… 
… 
… 
  Average 
Mean 
XX.X 
XX.X 
XX.X 
Programmers Notes:  
Please repeat table for the following subgroups: HIV-1 RNA level: HIV-1 RNA level: ≥2000 copies/mL, <2000 copies/mL); HIV-1 subtype (C / Other) and Schedule A, B or C 
- 
Table14.3.7.13.2 will be similar to Table14.3.7.13.1 but the heading and analysis will be based on Any Timepoint 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1; NNRTI = Non-nucleoside reverse transcriptase inhibitor ; NRTI = Nucleoside reverse transcriptase inhibitor; PI = Protease inhibitor 
Percentages are calculated out of the number of participants (per IPM 027 treatment) a In the virology population b Reported HIV-1 drug resistance-associated mutation 
Resistance-associated mutations were defined using the Stanford HIV database algorithm Version 8.4


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.14.1 
Summary of Mutational Patterns of Resistance-Associated Mutations at Seroconversion Timepoint 
Virology Population 
Subgroup: All IPM 032 participants 
 
Page 51 of 93 
 
Version 1.0 
26 Mar 2020 
 
Mutation Score Classification 
Statistic 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
 
 
 
 
 
Resistance categorization score 
N 
XX 
XX 
XX 
 
 
 
 
 
Susceptible  
 
 
 
 
Potential low-level resistant 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Low-level resistant 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
Intermediate resistant 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
High-level resistant 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note:  
Please repeat table for the following subgroups: HIV-1 RNA level: HIV-1 RNA level: ≥ 2000 copies/mL, < 2000 copies/mL); HIV-1 subtype (C / Other); Schedule A, B or C 
- 
Table14.3.14.2 will be similar to Table14.3.14.1 but the analysis and header will be based on Any Timepoint 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1; NNRTI = Non-nucleoside reverse transcriptase inhibitor; NRTI = Nucleoside reverse transcriptase inhibitor; PI = Protease inhibitor 
Percentages are calculated out of the number of (per IPM 027 treatment) a Participants in the virology population b Successful assessments 
Resistance-associated mutations were defined using the Stanford HIV database algorithm Version 8.4


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.15 
Timing Profile 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 52 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
IPM 027 
 
IPM 032 
 
Statistic 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 027 Overall 
(N=XXX) 
 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
 
Time on randomized IP 
n 
XXX 
XXX 
XXX 
 
 
 
 
 
Mean 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
 
 
 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
 
 
 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Time on open-label IP 
n 
XXX 
 
 
 
 
 
 
 
Mean 
XX.X 
 
 
 
 
 
 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
 
 
 
 
 
 
 
SD 
XX.XX 
 
 
 
 
 
 
 
(Min, Max) 
(XX, XX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total time on IP 
n 
XXX 
XXX 
XXX 
 
XXX 
XXX 
XXX 
 
Mean 
XX.X 
XX.X 
XX.X 
 
XX.X 
XX.X 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
XX.XX 
XX.XX 
 
XX.XX 
XX.XX 
XX.XX 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please repeat the table for the following subgroup: IPM 027 participants who directly enrolled in IPM 032. Note that the category ‘Time off IP between 
IPM 027 and IPM 032’ can be omitted for that subgroup. 
 
 
 
 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1; IP = Investigational product 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.15 
Timing Profile 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 53 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
IPM 027 
 
IPM 032 
 
Statistic 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 027 Overall 
(N=XXX) 
 
IPM 027 Dapivirine 
(N=XXX) 
IPM 027 Placebo 
(N=XXX) 
IPM 032 Overall 
(N=XXX) 
 
 
 
 
 
 
 
 
 
Time off IP between 
n 
 
 
 
 
XXX 
XXX 
XXX 
IPM 027 and IPM 032 
Mean 
 
 
 
 
XX.X 
XX.X 
XX.X 
 
(q1,med,q3) 
 
 
 
 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
 
 
 
 
XX.XX 
XX.XX 
XX.XX 
 
(Min, Max) 
 
 
 
 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
 
 
Time to first positive 
n 
 
 
 
 
XXX 
XXX 
XXX 
HIV-1 RNA 
Mean 
 
 
 
 
XX.X 
XX.X 
XX.X 
 
(q1,med,q3) 
 
 
 
 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
 
 
 
 
XX.XX 
XX.XX 
XX.XX 
 
(Min, Max) 
 
 
 
 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
 
 
Time to seroconversion 
n 
 
 
 
 
XXX 
XXX 
XXX 
 
Mean 
 
 
 
 
XX.X 
XX.X 
XX.X 
 
(q1,med,q3) 
 
 
 
 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
SD 
 
 
 
 
XX.XX 
XX.XX 
XX.XX 
 
(Min, Max) 
 
 
 
 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please repeat the table for the following subgroup: IPM 027 participants who directly enrolled in IPM 032. Note that the category ‘Time off IP between 
IPM 027 and IPM 032’ can be omitted for that subgroup. 
 
 
 
 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1; IP = Investigational product 
     


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.7.16 
Pregnancy Test Results 
Safety Population 
Subgroup: All IPM 032 participants 
 
Page 54 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
Centre 01 
… 
All Centres 
Visit 
Pregnancy Result 
Statistic 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
 (N=XXX) 
… 
IPM 027 
Dapivirine 
(N=XXX) 
IPM 027 
Placebo 
(N=XXX) 
IPM 032 
Overall 
 (N=XXX) 
 
 
 
 
 
 
 
 
 
 
Trial Month X / 
Positive / 
n (%)a 
X (  X.X)  
X (  X.X)  
X (  X.X) 
… 
X (  X.X)  
X (  X.X)  
X (  X.X)  
LPUV / 
Negative 
n (%)a 
X (  X.X)  
X (  X.X)  
X (  X.X)  
 
X (  X.X)  
X (  X.X)  
X (  X.X)  
All visits 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a Percentages are calculated out of the number of participants in the safety population per centre and IPM027 treatment 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.3.8.1 
Concomitant Medication 
Safety Population 
 
 
Page 55 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Statistic 
Centre 01 
(N=XXX) 
Centre 02 
(N=XXX) 
… 
Centre 08 
(N=XXX) 
All Centres 
(N=XXX) 
 
 
 
 
 
 
 
Participants with a reported concomitant medication  
n (%)a 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
ATC Level 2 
 
 
 
 
 
 
  Preferred name  
n (%)b 
X (  X.X) 
X (  X.X) 
… 
X (  X.X) 
X (  X.X) 
  … 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Percentages are calculated out of the number of participants (by centre) a In the safety population b Reported concomitant medication 
Concomitant medication is defined as any medication taken in conjunction with the investigational product (IP). This includes any medication that started after the first insertion of the IP, 
or started before the first insertion of the IP but ended on/after the first insertion of the IP. 
Medications were coded using WHO DDE (version June 2017) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.1 
Participant Report, Feasibility of 3-Monthly Clinical Follow-Up Schedule 
Safety Population 
 
 
Page 56 of 93 
 
Version 1.0 
26 Mar 2020 
 
Visit 
  Question of Interest 
    Response 
Statistic 
Schedule A 
(N=XXX) 
Schedule B 
(N=XXX) 
Schedule C 
(N=XXX) 
All Schedules 
(N=XXX) 
 
 
 
 
 
 
Trial Month X 
 
 
 
 
 
  Number of used/unused rings returned 
m 
XXX 
XXX 
XXX 
XXX 
  Number of rings dispensed 
M 
XXX 
XXX 
XXX 
XXX 
  The proportion of returned rings (used and unused) during the 3-monthly clinical follow-up 
  schedule will also be reported 
m/M 
XX.X 
XX.X 
XX.X 
XX.X 
  As per investigator decision are you coming to the research centre next month or in three  
  months for your next visit? 
 
 
 
 
 
    Next month 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    In three months 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  Will you take your extra rings with you today or will you come back to the research centre each  
  month to pick up your new ring? 
 
 
 
 
 
    Will take them all 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Will leave them at the research centre to collect monthly 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  What are your reasons for leaving the rings at the research centre today? 
 
 
 
 
 
    Do not want anyone to see the rings 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Do not have a private place to store unused rings 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Etc. 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
  If you were not in a study, would you prefer to come to the health care clinic / provider for new  
  rings each month, or every three months? 
 
 
 
 
 
    Each month 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Every three months 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Don’t mind 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Depends 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  If you were not in a study, would you prefer to come to the health care clinic / provider for an  
  HIV test each month, or every three months? 
 
 
 
 
 
    Each month 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Every three months 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Don’t mind 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Depends 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
a Percentages are calculated out of the number of participants in the safety population per visit schedule 
Visit Schedule A = Participants attended trial month visit 1, 4, 7, 10, 13 and 16/Exit 
Visit Schedule B = Participants attended trial month visit 1, 2, 5, 8, 11, 14 and 17/Exit 
Visit Schedule C = Participants attended trial month visit 1, 2, 3, 6, 9, 12 and 15/Exit


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.1 
Participant Report, Feasibility of 3-Monthly Clinical Follow-Up Schedule 
Safety Population 
 
 
Page 57 of 93 
 
Version 1.0 
26 Mar 2020 
 
Visit  
  Question of Interest 
    Response 
Statistic 
Schedule A 
(N=XXX) 
Schedule B 
(N=XXX) 
Schedule C 
(N=XXX) 
All Schedules 
(N=XXX) 
 
 
 
 
 
 
Trial Month X 
 
 
 
 
 
  Will you take your extra rings with you today or will you come back to the research centre  
  each month to pick up your new ring? 
 
 
 
 
 
    Will take them all 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Will leave them at the research centre to collect monthly 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  What are your reasons for leaving the rings at the research centre today? 
 
 
 
 
 
    Do not want anyone to see the rings 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Do not have a private place to store unused rings 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Etc. 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  If you were not in a study, would you prefer to come to the health care clinic / provider for new  
  rings each month, or every three months? 
 
 
 
 
 
    Each month 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Every three months 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Don’t mind 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Depends 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  If you were not in a study, would you prefer to come to the health care clinic / provider for an  
  HIV test each month, or every three months? 
 
 
 
 
 
    Each month 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Every three months 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Don’t mind 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Depends 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
a Percentages are calculated out of the number of participants in the safety population per visit schedule 
Visit Schedule A = Participants attended trial month visit 1, 4, 7, 10, 13 and 16/Exit 
Visit Schedule B = Participants attended trial month visit 1, 2, 5, 8, 11, 14 and 17/Exit 
Visit Schedule C = Participants attended trial month visit 1, 2, 3, 6, 9, 12 and 15/Exit 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.1 
Participant Report, Feasibility of 3-Monthly Clinical Follow-Up Schedule 
Safety Population 
 
 
Page 58 of 93 
 
Version 1.0 
26 Mar 2020 
 
Visit  
  Question of Interest 
    Response 
Statistic 
Schedule A 
(N=XXX) 
Schedule B 
(N=XXX) 
Schedule C 
(N=XXX) 
All Schedules 
(N=XXX) 
 
 
 
 
 
 
Trial Month X 
 
 
 
 
 
  When you were doing your three monthly visits, did you take your extra rings with you or  
  did you come back to the research centre each month to pick up your new ring? 
 
 
 
 
 
    Always took them  
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Always left them at the research centre to collect monthly 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Sometimes took them, sometimes left them at the research centre 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  What were your reasons for leaving the rings at the research centre? 
 
 
 
 
 
    Did not want anyone to see the rings 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Did not have a private place to store the unused rings 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Etc. 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  If you were not in a study, would you prefer to come to the health care clinic / provider for  
  new rings each month, or every three months? 
 
 
 
 
 
    Each month 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Every three months 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Don’t mind 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Depends 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
  If you were not in a study, would you prefer to come to the health care clinic / provider for  
  an HIV test each month, or every three months? 
 
 
 
 
 
    Each month 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Every three months 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Don’t mind 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
    Depends 
n (%)a 
X (  X.X) 
X (  X.X) 
X (  X.X) 
X (  X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
a Percentages are calculated out of the number of participants in the safety population per visit schedule 
Visit Schedule A = Participants attended trial month visit 1, 4, 7, 10, 13 and 16/Exit 
Visit Schedule B = Participants attended trial month visit 1, 2, 5, 8, 11, 14 and 17/Exit 
Visit Schedule C = Participants attended trial month visit 1, 2, 3, 6, 9, 12 and 15/Exir


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.2 
Correlation Between Dapivirine Residual Levels (mg) and Results From Visual Inspection of Returned Vaginal Rings 
Safety Population 
 
 
Page 59 of 93 
 
Version 1.0 
26 Mar 2020 
 
Month Ring Used 
Appearance 
Statistic 
White to Off-White 
Slight Yellow to Yellow 
Tan 
Brown 
Other 
 
 
 
 
 
 
 
 
Trial month X / 
Used 
n 
XXX 
XXX 
XXX 
XXX 
XXX 
Exit visit 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
 
 
Unused 
n 
XXX 
XXX 
XXX 
XXX 
XXX 
 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
 
 
Not sure 
n 
XXX 
XXX 
XXX 
XXX 
XXX 
 
 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
(XX.X,XX.X,XX.X) 
 
 
SD 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
XX.XX 
 
 
(Min, Max) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
(XX, XX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.3 
Proportion of Participants Opting for HIV Rapid Tests at the Research Centre Between Scheduled 3-Monthly Visits 
Safety Population 
 
 
Page 60 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
(N=XXX) 
 
 
 
Number of participants with at least one HIV rapid test performed at an unscheduled visit 
n (%)a 
X ( X.X) 
 
 
 
Total number of participants with at least one HIV rapid test performed at any visit 
n (%)a 
X ( X.X) 
 
 
 
Proportion of participants undergoing HIV rapid tests at the research centre between scheduled 3-monthly follow up visits 
p (%) 
X.X (XX.X) 
 
 
 
 
 
 
a Percentages are calculated out of the number of participants in the safety population 
p = (Number of participants with at least one HIV rapid test performed at an unscheduled visit) / (total number of participants with at least one HIV rapid test performed at any visit) 
 
 
 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.4 
Social Harms Report 
Safety Population 
 
 
Page 61 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
(N=XXX) 
 
 
 
Participants who reported any social harm 
n (%)a m 
X ( X.X) X 
 
 
 
Responses by participants 
 
 
Has a similar event happened before? 
 
 
  Yes 
n (%)b m 
X ( X.X) X 
  No 
n (%)b m 
X ( X.X) X 
  Not reported 
n (%)b m 
X ( X.X) X 
Due to trial involvement? 
 
 
  Yes 
n (%)b m 
X ( X.X) X 
  No 
n (%)b m 
X ( X.X) X 
  Not sure 
n (%)b m 
X ( X.X) X 
  Not reported 
n (%)b m 
X ( X.X) X 
Is the situation resolved? 
 
 
  Yes 
n (%)b m 
X ( X.X) X 
  No 
n (%)b m 
X ( X.X) X 
  Not sure 
n (%)b m 
X ( X.X) X 
  Not reported 
n (%)b m 
X ( X.X) X 
Impact on quality of life 
 
 
  Minor disturbance 
n (%)b m 
X ( X.X) X 
  Moderate disturbance 
n (%)b m 
X ( X.X) X 
  Major disturbance 
n (%)b m 
X ( X.X) X 
 
 
 
Responses by research centre 
 
 
Type of social harm 
n (%)b m 
X ( X.X) X 
  Physical 
n (%)b m 
X ( X.X) X 
  Emotional 
n (%)b m 
X ( X.X) X 
  Financial 
n (%)b m 
X ( X.X) X 
  Not reported 
n (%)b m 
X ( X.X) X 
 
 
 
 
 
 
Percentages are calculated out of the number of participants a In the safety population b Reported social harm 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.4 
Social Harms Report 
Safety Population 
 
 
Page 62 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
(N=XXX) 
 
 
 
Actions taken by participant 
 
 
  None 
n (%)b m 
X ( X.X) X 
  Sought support services 
n (%)b m 
X ( X.X) X 
  Sought counseling 
n (%)b m 
X ( X.X) X 
  Sought medical care 
n (%)b m 
X ( X.X) X 
  Other 
n (%)b m 
X ( X.X) X 
  Not reported 
n (%)b m 
X ( X.X) X 
 
 
 
Actions taken by research centre 
 
 
  None 
n (%)b m 
X ( X.X) X 
  Referred to support services 
n (%)b m 
X ( X.X) X 
  Referred for counseling 
n (%)b m 
X ( X.X) X 
  Medical care 
n (%)b m 
X ( X.X) X 
  Other 
n (%)b m 
X ( X.X) X 
  Not reported 
n (%)b m 
X ( X.X) X 
 
 
 
Resolution status 
n (%)b m 
X ( X.X) X 
  Resolved 
n (%)b m 
X ( X.X) X 
  Unresolved 
n (%)b m 
X ( X.X) X 
  Ongoing at participant’s last visit 
 
 
 
 
 
 
 
 
Percentages are calculated out of the number of a Participants in the safety population b Social harms reported 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.5 
Participant Questionnaire – Part A (Month 1, 2, and 3) 
Safety Population 
Trial Month 1 
 
Page 63 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Investigator decision on next visit 
 
 
  Next month 
n (%)a 
X ( X.X) 
  In three months time 
n (%)a 
X ( X.X) 
 
 
 
Decision on extra rings 
 
 
  Will take them all 
n (%)a 
X ( X.X) 
  Will leave them at the research centre to collect monthly 
n (%)a 
X ( X.X) 
 
 
 
Reasons for leaving the rings at research centre today 
 
 
  Do not want anyone to see the rings 
n (%)b 
X ( X.X) 
  Do not have a private place to keep the unused rings at home 
n (%)b 
X ( X.X) 
  Do not have a private place to keep the used rings at home 
n (%)b 
X ( X.X) 
  Do not have an appropriate storage place to keep the rings (used/unused) at home 
n (%)b 
X ( X.X) 
  Do not have a private place to insert the rings at home 
n (%)b 
X ( X.X) 
  Worried I might lose the ring(s) 
n (%)b 
X ( X.X) 
  Feel I might forget to insert a new ring if I don’t come each month 
n (%)b 
X ( X.X) 
  Like coming to the research centre for HIV tests each month 
n (%)b 
X ( X.X) 
  Like coming to the research centre monthly for social reasons 
n (%)b 
X ( X.X) 
  Other 
n (%)b 
X ( X.X) 
 
 
 
Main partner knowledge of the vaginal ring and study participation 
 
 
  With main partner 
n (%)a 
X ( X.X) 
  He knows about the study and the ring 
n (%)c 
X ( X.X) 
  He only knows that I am in the study 
n (%)c 
X ( X.X) 
  He only knows that I am wearing a ring 
n (%)c 
X ( X.X) 
  He doesn’t know about the study or the ring 
n (%)c 
X ( X.X) 
  Don’t know 
n (%)c 
X ( X.X) 
 
 
 
Programmers Notes: 
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for Trial Month 2 and Trial Month 3 
 
 
 
Percentages are calculated out of number of participants a In the safety population b Left rings at the research centre c With main partner 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.5 
Participant Questionnaire – Part A (Month 1, 2, and 3) 
Safety Population 
Trial Month 1 
 
Page 64 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
View on the information sheet 
 
 
  The sheet is good as it is 
n (%)a 
X ( X.X) 
  The sheet is hard to understand 
n (%)a 
X ( X.X) 
  The sheet needs more information 
n (%)a 
X ( X.X) 
  The sheet needs to be changed 
n (%)a 
X ( X.X) 
  Did not read the instruction sheet 
n (%)a 
X ( X.X) 
  Can’t remember (the instruction sheet) 
 
 
 
 
 
 
 
 
Programmers Notes: 
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for Trial Month 2 and Trial Month 3 
 
 
 
Percentages are calculated out of number of participants a In the safety population b Left rings at the research centre c With main partner 
 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.6 
Participant Questionnaire – Part B (Month  2 and 3 only) 
Safety Population 
Trial Month 2 
 
Page 65 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Ring removed/expelled since last scheduled visit? 
 
 
  Yes 
n (%)a 
X ( X.X) 
  No 
n (%)a 
X ( X.X) 
 
 
 
Reason why the ring was removed/expelled 
 
 
  Took it out because it was uncomfortable/painful 
n (%)b 
X ( X.X) 
  Took it out to clean the ring 
n (%)b 
X ( X.X) 
  Took it out because on menses 
n (%)b 
X ( X.X) 
  Took it out because of real/perceived side effects 
n (%)b 
X ( X.X) 
  Took it out because partner requested it 
n (%)b 
X ( X.X) 
  Took it out for sex 
n (%)b 
X ( X.X) 
  Took it out so that partner did not find out about it 
n (%)b 
X ( X.X) 
  Accidentally came out 
n (%)b 
X ( X.X) 
  Other 
n (%)b 
X ( X.X) 
 
 
 
When the ring was removed/expelled did you clean the ring before reinsertion? 
 
 
  Yes 
n (%)b 
X ( X.X) 
  No 
n (%)b 
X ( X.X) 
 
 
 
What did you use to clean the ring when it was removed/expelled? 
 
 
  Water only 
n (%)c 
X ( X.X) 
  Soap only 
n (%)c 
X ( X.X) 
  Water and soap 
n (%)c 
X ( X.X) 
  Disinfectant 
n (%)c 
X ( X.X) 
  Herbal products 
n (%)c 
X ( X.X) 
  Traditional medicine 
n (%)c 
X ( X.X) 
  Bubble bath 
n (%)c 
X ( X.X) 
  Bath salts 
n (%)c 
X ( X.X) 
  Dishwashing liquid 
n (%)c 
X ( X.X) 
  Other 
n (%)c 
X ( X.X) 
 
 
 
Programmers Notes:  
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for Trial Month 3 
 
 
Percentages are calculated out of the number of participants a In the safety population b Whose ring was expelled/removed since last visit c Cleaned ring before reinsertion 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.6 
Participant Questionnaire – Part B (Month  2 and 3 only) 
Safety Population 
Trial Month 2 
 
Page 66 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Since your last scheduled visit, was it easy or difficult to remove your ring? 
 
 
  Easy to remove 
n (%)b 
X ( X.X) 
  Difficult to remove 
n (%)b 
X ( X.X) 
  Sometimes easy, sometimes difficult to remove 
n (%)b 
X ( X.X) 
  Neither easy nor difficult to remove 
n (%)b 
X ( X.X) 
  N/A, I did not remove my own ring 
n (%)b 
X ( X.X) 
 
 
 
Since your last scheduled visit, was it easy or difficult to insert a new ring? 
 
 
  Easy to insert 
n (%)b 
X ( X.X) 
  Difficult to insert 
n (%)b 
X ( X.X) 
  Sometimes easy, sometimes difficult to insert 
n (%)b 
X ( X.X) 
  Neither easy nor difficult to insert 
n (%)b 
X ( X.X) 
  N/A, I did not insert my own ring 
n (%)b 
X ( X.X) 
 
 
 
Blood sample preferences 
 
 
  It is fine to have a blood sample taken at every visit 
n (%)a 
X ( X.X) 
  Prefer to have blood sample taken less often 
n (%)a 
X ( X.X) 
 
 
 
Vaginal fluid sample preferences 
 
 
  It is fine to have a vaginal fluid sample taken at every visit 
n (%)a 
X ( X.X) 
  Prefer to have vaginal fluid sample taken less often 
n (%)a 
X ( X.X) 
 
 
 
Experienced any of the following in the study 
 
 
  Length of time spent at the research centre for the study visits was too long 
n (%)a 
X ( X.X) 
  Transport to the research centre for scheduled visits was a problem 
n (%)a 
X ( X.X) 
  I was treated well when coming to the research centre for regular visits 
n (%)a 
X ( X.X) 
  Partner is happy about participation (if he is aware of participation) 
n (%)a 
X ( X.X) 
  My neighbors, family, or friends know about my participation in this study 
n (%)a 
X ( X.X) 
  My neighbors, family, or friends (as above) are happy about my participation in this study (if they are aware of participation) 
n (%)a 
X ( X.X) 
  Other 
n (%)a 
X ( X.X) 
 
 
 
Programmers Notes:  
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for Trial Month 3 
Percentages are calculated out of the number of participants a In the safety population b Cleaned ring before reinsertion 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.6 
Participant Questionnaire – Part B (Month  2 and 3 only) 
Safety Population 
Trial Month 2 
 
Page 67 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Preference if not in the DREAM study: Prefer to come to the health care clinic/provider for new rings each month or every three months 
 
 
  Each month 
n (%)a 
X ( X.X) 
  Every three months 
n (%)a 
X ( X.X) 
  Don’t mind 
n (%)a 
X ( X.X) 
  Depends 
n (%)a 
X ( X.X) 
 
 
 
Preference if not in the DREAM study: Prefer to come to the health care clinic/provider for HIV tests each month or every three months 
 
 
  Each month 
n (%)a 
X ( X.X) 
  Every three months 
n (%)a 
X ( X.X) 
  Don’t mind 
n (%)a 
X ( X.X) 
  Depends 
n (%)a 
X ( X.X) 
 
 
 
Programmers Notes:  
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for Trial Month 3 
 
 
 
Percentages are calculated out of the number of participants a In the safety population b Whose ring was expelled/removed since last visit c Cleaned ring before reinsertion 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.7 
Participant Questionnaire – Part C (Month  1, 2, and 3) 
Safety Population 
Trial Month 1 
 
Page 68 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Currently have a main sex partner 
 
 
  Yes 
n (%)a 
X ( X.X) 
  No 
n (%)a 
X ( X.X) 
 
 
 
Currently live with main partner 
 
 
  Yes 
n (%)b 
X ( X.X) 
  No 
n (%)b 
X ( X.X) 
 
 
 
Other partners in the past three months 
 
 
  0  
n (%)a 
X ( X.X) 
  1 
n (%)a 
X ( X.X) 
  2 or more 
n (%)a 
X ( X.X) 
 
 
 
Number of sex acts over the past month 
Mean 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
 
(Min, Max) 
(XX, XX) 
Use of a male condom over the past month 
 
 
  Always 
n (%)a 
X ( X.X) 
  Sometimes 
n (%)a 
X ( X.X) 
  Often 
n (%)a 
X ( X.X) 
  Never 
n (%)a 
X ( X.X) 
 
 
 
Programmers Notes:  
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for Trial Month 2 and Trial Month 3 
 
 
Percentages are calculated out of the number of participants a In the safety population b Has main partner c Used a condom d Had a menstrual bleeding/spotting in past three months  
e Inserted fingers into vagina 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.7 
Participant Questionnaire – Part C (Month  1, 2, and 3) 
Safety Population 
Trial Month 1 
 
Page 69 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Use of a female condom over the past month 
 
 
  Always 
n (%)a 
X ( X.X) 
  Sometimes 
n (%)a 
X ( X.X) 
  Often 
n (%)a 
X ( X.X) 
  Never 
n (%)a 
X ( X.X) 
 
 
 
Used a condom during last round of vaginal sex 
 
 
  No 
n (%)a 
X ( X.X) 
  Yes 
n (%)a 
X ( X.X) 
     Male condom 
 
 
     Female condom 
 
 
 
 
 
Had anal sex during the last year 
 
 
  No 
n (%)a 
X ( X.X) 
  Yes 
n (%)a 
X ( X.X) 
     Used a condom 
n (%)a 
X ( X.X) 
     Did not use a condom 
n (%)a 
X ( X.X) 
 
 
 
Level of being worried about getting infected with HIV in the next year 
 
 
  Very worried 
n (%)a 
X ( X.X) 
  A little worried 
n (%)a 
X ( X.X) 
  Not worried at all 
n (%)a 
X ( X.X) 
 
 
 
Had menstrual bleeding/spotting in the past 3 months 
 
 
  Yes 
n (%)a 
X ( X.X) 
  No 
n (%)a 
X ( X.X) 
 
 
 
Programmers Notes:  
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for Trial Month 2 and Trial Month 3 
Percentages are calculated out of the number of participants a In the safety population b Has main partner c Used a condom d Had a menstrual bleeding/spotting in past three months  
e Inserted fingers into vagina 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.7 
Participant Questionnaire – Part C (Month  1, 2, and 3) 
Safety Population 
Trial Month 1 
 
Page 70 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Products used in the past 3 months to control menstrual bleeding/spotting 
 
 
  Tissue, toilet paper, paper, cloth or cotton wool put inside the vagina 
n (%)d 
X ( X.X) 
  Tissue, toilet paper, paper, cloth or cotton wool put inside the underwear/clothing 
n (%)d 
X ( X.X) 
  Tampon 
n (%)d 
X ( X.X) 
  Sanitary pad 
n (%)d 
X ( X.X) 
  Menstrual cup 
n (%)d 
X ( X.X) 
  Water without soap (inside the vagina) 
n (%)d 
X ( X.X) 
  Water with soap (inside the vagina) 
n (%)d 
X ( X.X) 
  Nothing was used 
n (%)d 
X ( X.X) 
  Other 
n (%)d 
X ( X.X) 
 
 
 
Inserted fingers into vagina since last schedule visit 
 
 
  Yes 
n (%)a 
X ( X.X) 
  No 
n (%)a 
X ( X.X) 
 
 
 
Reason for inserting fingers into vagina 
n (%)d 
X ( X.X) 
  Check the position of the ring 
n (%)d 
X ( X.X) 
  Insert/remove the ring 
n (%)d 
X ( X.X) 
  Cleaning 
n (%)d 
X ( X.X) 
  Sexual pleasure 
n (%)d 
X ( X.X) 
  Insert a product for the management of menses 
n (%)d 
X ( X.X) 
  Other 
n (%)d 
X ( X.X) 
 
 
 
Programmers Notes:  
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for Trial Month 2 and Trial Month 3 
 
 
 
Percentages are calculated out of the number of participants a In the safety population b Has main partner c Used a condom d Had a menstrual bleeding/spotting in past three months  
e Inserted fingers into vagina 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.8 
Participant Questionnaire – 3 Month Follow-Up 
Safety Population 
Trial Month X 
 
Page 71 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Decision to take the rings today or leave them at the research centre to collect monthly 
n (%)a 
X ( X.X) 
  Will take them all 
n (%)a 
X ( X.X) 
  Will leave them at the research centre to collect monthly 
 
 
 
 
 
Reasons for leaving the rings at research centre today 
 
 
  Do not want anyone to see the rings 
n (%)b 
X ( X.X) 
  Do not have a private place to keep the unused rings at home 
n (%)b 
X ( X.X) 
  Do not have a private place to keep the used rings at home 
n (%)b 
X ( X.X) 
  Do not have an appropriate storage place to keep the rings (used/unused) at home 
n (%)b 
X ( X.X) 
  Do not have a private place to insert the rings at home 
n (%)b 
X ( X.X) 
  Worried I might lose the ring(s) 
n (%)b 
X ( X.X) 
  Feel I might forget to insert a new ring if I don’t come each month 
n (%)b 
X ( X.X) 
  Like coming to the research centre for HIV tests each month 
n (%)b 
X ( X.X) 
  Like coming to the research centre monthly for social reasons 
n (%)b 
X ( X.X) 
  Other 
n (%)b 
X ( X.X) 
 
 
 
Additional HIV test when returned to the research centre to collect the ring 
 
 
  Yes 
n (%)b 
X ( X.X) 
  No 
n (%)b 
X ( X.X) 
  N/A 
n (%)b 
X ( X.X) 
 
 
 
Main partner knowledge of the vaginal ring and study participation 
 
 
  He knows about the study and the ring 
n (%)c 
X ( X.X) 
  He only knows that I am in the study 
n (%)c 
X ( X.X) 
  He only knows that I am wearing a ring 
n (%)c 
X ( X.X) 
  He doesn’t know about the study or the ring 
n (%)c 
X ( X.X) 
  Don’t know 
n (%)c 
X ( X.X) 
 
 
 
Programmers Notes:  
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for all available Trial Months 
Percentages are calculated out of the number of participants a In the safety population b Left rings at the research centre c With main partner d Took rings  
e Used a condom f Had anal sex since last visit g Had a menstrual bleeding/spotting since last visit h Had ring expelled/removed since last visit  
i Cleaned ring before reinsertion j Inserted fingers into vagina


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.8 
Participant Questionnaire – 3 Month Follow-Up 
Safety Population 
Trial Month X 
 
Page 72 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
View on the information sheet 
 
 
  The sheet is good as it is 
n (%)a 
X ( X.X) 
  The sheet is hard to understand 
n (%)a 
X ( X.X) 
  The sheet needs more information 
n (%)a 
X ( X.X) 
  The sheet needs to be changed 
n (%)a 
X ( X.X) 
  Did not read the instruction sheet 
n (%)a 
X ( X.X) 
  Can’t remember (the instruction sheet) 
n (%)a 
X ( X.X) 
 
 
 
Since your last scheduled visit, was it easy or difficult to remove your ring? 
 
 
  Easy to remove 
n (%)h 
X ( X.X) 
  Difficult to remove 
n (%)h 
X ( X.X) 
  Sometimes easy, sometimes difficult to remove 
n (%)h 
X ( X.X) 
  Neither easy nor difficult to remove 
n (%)h 
X ( X.X) 
  N/A, I did not remove my own ring 
n (%)h 
X ( X.X) 
 
 
 
Since your last scheduled visit, was it easy or difficult to insert a new ring? 
 
 
  Easy to insert 
n (%)h 
X ( X.X) 
  Difficult to insert 
n (%)h 
X ( X.X) 
  Sometimes easy, sometimes difficult to insert 
n (%)h 
X ( X.X) 
  Neither easy nor difficult to insert 
n (%)h 
X ( X.X) 
  N/A, I did not insert my own ring 
n (%)h 
X ( X.X) 
 
 
 
Programmers Notes:  
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for all available Trial Months 
Percentages are calculated out of the number of participants a In the safety population b Left rings at the research centre c With main partner d Took rings  
e Used a condom f Had anal sex since last visit g Had a menstrual bleeding/spotting since last visit h Had ring expelled/removed since last visit  
i Cleaned ring before reinsertion j Inserted fingers into vagina


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.8 
Participant Questionnaire – 3 Month Follow-Up 
Safety Population 
Trial Month X 
 
Page 73 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Experience with the bag given to put the used rings in 
 
 
  The bag was easy to open and close 
n (%)a 
X ( X.X) 
  The bag was hard to open and close 
n (%)a 
X ( X.X) 
  The bag was sometimes lost 
n (%)a 
X ( X.X) 
  The bag was sometimes used for something else 
n (%)a 
X ( X.X) 
  The bag was fine 
n (%)a 
X ( X.X) 
  I did not like having to keep the empty bag(s) 
n (%)a 
X ( X.X) 
  I did not like having the used ring(s) in the house 
n (%)a 
X ( X.X) 
  I did not like carrying the used ring(s) to the research centre 
n (%)a 
X ( X.X) 
  Someone found the ring bag(s) (with or without rings), 
n (%)a 
X ( X.X) 
  I did not like the look of the bag 
n (%)a 
X ( X.X) 
  It was difficult to bring the bags back to the clinic 
n (%)a 
X ( X.X) 
  Other 
n (%)a 
X ( X.X) 
  Not applicable, I did not use the bags or return a ring since the last visit 
n (%)a 
X ( X.X) 
 
 
 
Place of storage of the unused ring(s) before insertion 
n (%)d 
X ( X.X) 
  In bag/handbag 
n (%)d 
X ( X.X) 
  In a shared cupboard/drawer in the house 
n (%)d 
X ( X.X) 
  In a personal cupboard/drawer in my room/in the house 
n (%)d 
X ( X.X) 
  In a locked place that no-one else could access 
n (%)d 
X ( X.X) 
  At someone else’s house 
n (%)d 
X ( X.X) 
  Other 
n (%)d 
X ( X.X) 
  Not applicable, I did not have any extra unused rings since the last visit 
n (%)d 
X ( X.X) 
 
 
 
Programmers Notes:  
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for all available Trial Months 
 
 
Percentages are calculated out of the number of participants a In the safety population b Left rings at the research centre c With main partner d Took rings  
e Used a condom f Had anal sex since last visit g Had a menstrual bleeding/spotting since last visit h Had ring expelled/removed since last visit  
i Cleaned ring before reinsertion j Inserted fingers into vagina


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.8 
Participant Questionnaire – 3 Month Follow-Up 
Safety Population 
Trial Month X 
 
Page 74 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
Experience when storing the unused ring(s) 
 
 
  There were no problems storing the unused ring(s) 
n (%)d 
X ( X.X) 
  I was concerned that someone might find the unused ring 
n (%)d 
X ( X.X) 
  I sometimes forgot where I had stored the unused ring(s)/lost the unused ring(s) 
n (%)d 
X ( X.X) 
  The ring(s) accidentally got thrown away 
n (%)d 
X ( X.X) 
  I did not like storing the unused rings 
n (%)d 
X ( X.X) 
  Someone found the ring(s) and that was problematic 
n (%)d 
X ( X.X) 
  Someone found the ring(s) but it was not problematic 
n (%)d 
X ( X.X) 
  Other 
n (%)d 
X ( X.X) 
  Not applicable, I did not have any extra unused rings since the last visit 
n (%)d 
X ( X.X) 
 
 
 
Place of storage of the used ring(s) after removal 
 
 
  I returned the used ring(s) to the research centre straight away 
n (%)h 
X ( X.X) 
  In a bag/handbag 
n (%)h 
X ( X.X) 
  In a shared cupboard/drawer in the house 
n (%)h 
X ( X.X) 
  In a personal cupboard/drawer in my room/in the house 
n (%)h 
X ( X.X) 
  In a locked place that no-one else could access 
n (%)h 
X ( X.X) 
  At someone else’s house 
n (%)h 
X ( X.X) 
  Other 
n (%)h 
X ( X.X) 
  Not applicable, I did not store any extra used rings since the last visit 
n (%)h 
X ( X.X) 
 
 
 
Experience when storing the used ring 
 
 
  There were no problems storing the used ring 
n (%)h 
X ( X.X) 
  I was concerned that someone might find the used ring 
n (%)h 
X ( X.X) 
  I sometimes forgot where I had stored the used ring(s)/lost the used ring(s) 
n (%)h 
X ( X.X) 
  The ring accidentally got thrown away 
n (%)h 
X ( X.X) 
  I did not like storing the used rings 
n (%)h 
X ( X.X) 
  Someone found the ring(s) and that was problematic 
n (%)h 
X ( X.X) 
  Someone found the ring(s) but it was not problematic 
n (%)h 
X ( X.X) 
  Other 
n (%)h 
X ( X.X) 
  Not applicable, I did not store any extra used rings since the last visit 
n (%)h 
X ( X.X) 
Programmers Notes:  
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for all available Trial Months 
 
 
Percentages are calculated out of the number of participants a In the safety population b Left rings at the research centre c With main partner d Took rings  
e Used a condom f Had anal sex since last visit g Had a menstrual bleeding/spotting since last visit h Had ring expelled/removed since last visit  
i Cleaned ring before reinsertion j Inserted fingers into vagina


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.8 
Participant Questionnaire – 3 Month Follow-Up 
Safety Population 
Trial Month X 
 
Page 75 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Blood sample preferences 
 
 
  It is fine to have a blood sample taken at every visit 
n (%)a 
X ( X.X) 
  Prefer to have blood sample taken less often 
n (%)a 
X ( X.X) 
 
 
 
Vaginal fluid sample preferences 
 
 
  It is fine to have a vaginal fluid sample taken at every visit 
n (%)a 
X ( X.X) 
  Prefer to have vaginal fluid sample taken less often 
n (%)a 
X ( X.X) 
 
 
 
Experienced any of the following in the study 
 
 
  Length of time spent at the research centre for the study visits was too long 
n (%)a 
X ( X.X) 
  Length of time spent at the research centre to pick up rings was too long 
n (%)a 
X ( X.X) 
  Transport to the research centre for scheduled visits was a problem 
n (%)a 
X ( X.X) 
  I was treated well when coming to the research centre for regular visits 
n (%)a 
X ( X.X) 
  I was treated well when I came to the research centre to pick up rings 
n (%)a 
X ( X.X) 
  Transport to pick up rings was a problem 
n (%)a 
X ( X.X) 
  Partner is happy about participation (if he is aware of participation) 
n (%)a 
X ( X.X) 
  My neighbors, family, or friends know about my participation in this study 
n (%)a 
X ( X.X) 
  My neighbors, family, or friends (as above) are happy about my participation in this study (if they are aware of participation) 
n (%)a 
X ( X.X) 
  Other 
n (%)a 
X ( X.X) 
 
 
 
Preference if not in the DREAM study: Prefer to come to the health care clinic/provider for new rings each month or every three months 
 
 
  Each month 
n (%)a 
X ( X.X) 
  Every three months 
n (%)a 
X ( X.X) 
  Don’t mind 
n (%)a 
X ( X.X) 
  Depends 
n (%)a 
X ( X.X) 
 
 
 
Programmers Notes:  
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for all available Trial Months 
 
 
Percentages are calculated out of the number of participants a In the safety population b Who left their rings at the research centre c With main partner d Who took their rings  
e Who used a condom f Who had anal sex since last visit g Who had a menstrual bleeding/spotting since last visit h Who had ring expelled/removed since last visit  
i Who cleaned ring before reinsertion j Who inserted fingers into their vaginas 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.8 
Participant Questionnaire – 3 Month Follow-Up 
Safety Population 
Trial Month X 
 
Page 76 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Preference if not in the DREAM study: Prefer to come to the health care clinic/provider for HIV tests each month or every three months 
 
 
  Each month 
n (%)a 
X ( X.X) 
  Every three months 
n (%)a 
X ( X.X) 
  Don’t mind 
n (%)a 
X ( X.X) 
  Depends 
n (%)a 
X ( X.X) 
 
 
 
Currently have a main sex partner 
 
 
  Yes 
n (%)a 
X ( X.X) 
  No 
n (%)a 
X ( X.X) 
 
 
 
Currently live with main partner 
 
 
  Yes 
n (%)b 
X ( X.X) 
  No 
n (%)b 
X ( X.X) 
 
 
 
Other partners since last scheduled visit 
 
 
  0 - 1 
n (%)a 
X ( X.X) 
  >= 2 
n (%)a 
X ( X.X) 
 
 
 
Number of sex acts over the past month 
Mean 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
 
(Min, Max) 
(XX, XX) 
 
 
 
Use of a male condom over the past month 
 
 
  Always 
n (%)a 
X ( X.X) 
  Sometimes 
n (%)a 
X ( X.X) 
  Often 
n (%)a 
X ( X.X) 
  Never 
n (%)a 
X ( X.X) 
 
 
 
Programmers Notes:  
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for all available Trial Months 
 
 
Percentages are calculated out of the number of participants a In the safety population b Who left their rings at the research centre c With main partner d Who took their rings  
e Who used a condom f Who had anal sex since last visit g Who had a menstrual bleeding/spotting since last visit h Who had ring expelled/removed since last visit  
i Who cleaned ring before reinsertion j Who inserted fingers into their vaginas 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.8 
Participant Questionnaire – 3 Month Follow-Up 
Safety Population 
Trial Month X 
 
Page 77 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
(N=XXX) 
 
 
 
Use of a female condom over the past month 
 
 
  Always 
n (%)a 
X ( X.X) 
  Sometimes 
n (%)a 
X ( X.X) 
  Often 
n (%)a 
X ( X.X) 
  Never 
n (%)a 
X ( X.X) 
 
 
 
Used a condom during last round of vaginal sex 
 
 
  No 
n (%)a 
X ( X.X) 
  Yes 
n (%)a 
X ( X.X) 
    Male condom 
n (%)e 
X ( X.X) 
    Female condom 
n (%)e 
X ( X.X) 
 
 
 
Had anal sex since last scheduled visit 
 
 
  No 
n (%)a 
X ( X.X) 
  Yes 
n (%)a 
X ( X.X) 
     Used a condom 
n (%)f 
X ( X.X) 
     Did not use a condom 
n (%)f 
X ( X.X) 
 
 
 
Level of being worried about getting infected with HIV in the next year 
 
 
  Very worried 
n (%)a 
X ( X.X) 
  A little worried 
n (%)a 
X ( X.X) 
  Not worried at all 
n (%)a 
X ( X.X) 
 
 
 
Had menstrual bleeding/spotting since last scheduled visit 
 
 
  Yes 
n (%)a 
X ( X.X) 
  No 
n (%)a 
X ( X.X) 
 
 
 
Programmers Notes:  
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for all available Trial Months 
 
 
Percentages are calculated out of the number of participants a In the safety population b Left rings at the research centre c With main partner d Took rings  
e Used a condom f Had anal sex since last visit g Had a menstrual bleeding/spotting since last visit h Had ring expelled/removed since last visit  
i Cleaned ring before reinsertion j Inserted fingers into vagina


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.8 
Participant Questionnaire – 3 Month Follow-Up 
Safety Population 
Trial Month X 
 
Page 78 of 93 
 
Version 1.0 
26 Mar 2020 
 
Percentages are calculated out of the number of participants a In the safety population b Left rings at the research centre c With main partner d Took rings  
e Used a condom f Had anal sex since last visit g Had a menstrual bleeding/spotting since last visit h Had ring expelled/removed since last visit  
i Cleaned ring before reinsertion j Inserted fingers into vagina
 
Statistic 
IPM 032 Overall 
(N=XXX) 
Products used in the past 3 months to control menstrual bleeding/spotting 
 
 
  Tissue, toilet paper, paper, cloth or cotton wool put inside the vagina 
n (%)g 
X ( X.X) 
  Tissue, toilet paper, paper, cloth or cotton wool put inside the underwear/clothing 
n (%)g 
X ( X.X) 
  Tampon 
n (%)g 
X ( X.X) 
  Sanitary pad 
n (%)g 
X ( X.X) 
  Menstrual cup 
n (%)g 
X ( X.X) 
  Water without soap (inside the vagina) 
n (%)g 
X ( X.X) 
  Water with soap (inside the vagina) 
n (%)g 
X ( X.X) 
  Nothing was used 
n (%)g 
X ( X.X) 
  Other 
n (%)g 
X ( X.X) 
 
 
 
Ring removed/expelled since last scheduled visit? 
 
 
  Yes 
n (%)a 
X ( X.X) 
  No 
n (%)a 
X ( X.X) 
 
 
 
Reason why the ring was removed/expelled 
 
 
  Took it out because it was uncomfortable/painful 
n (%)h 
X ( X.X) 
  Took it out to clean the ring 
n (%)h 
X ( X.X) 
  Took it out because on menses 
n (%)h 
X ( X.X) 
  Took it out because of real/perceived side effects 
n (%)h 
X ( X.X) 
  Took it out because partner requested it 
n (%)h 
X ( X.X) 
  Took it out for sex 
n (%)h 
X ( X.X) 
  Took it out so that partner did not find out about it 
n (%)h 
X ( X.X) 
  Accidentally came out 
n (%)h 
X ( X.X) 
  Other 
n (%)h 
X ( X.X) 
 
 
 
When the ring was removed/expelled did you clean the ring before reinsertion? 
 
 
  Yes 
n (%)h 
X ( X.X) 
  No 
n (%)h 
X ( X.X) 
 
 
 
Programmers Notes:  
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for all available Trial Months 
 
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.8 
Participant Questionnaire – 3 Month Follow-Up 
Safety Population 
Trial Month X 
 
Page 79 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
What did you use to clean the ring when it was removed/expelled? 
 
 
  Water only 
n (%)i 
X ( X.X) 
  Soap only 
n (%)i 
X ( X.X) 
  Water and soap 
n (%)i 
X ( X.X) 
  Disinfectant 
 
 
  Water and soap 
n (%)i 
X ( X.X) 
  Disinfectant 
n (%)i 
X ( X.X) 
  Herbal products 
n (%)i 
X ( X.X) 
  Traditional medicine 
n (%)i 
X ( X.X) 
  Bubble bath 
n (%)i 
X ( X.X) 
  Bath salts 
n (%)i 
X ( X.X) 
  Dishwashing liquid 
n (%)i 
X ( X.X) 
  Other 
n (%)i 
X ( X.X) 
 
 
 
Inserted fingers into vagina since last schedule visit 
 
 
  Yes 
n (%)a 
X ( X.X) 
  No 
n (%)a 
X ( X.X) 
 
 
 
Reason for inserting fingers into vagina 
n (%)j 
X ( X.X) 
  Check the position of the ring 
n (%)j 
X ( X.X) 
  Insert/remove the ring 
n (%)j 
X ( X.X) 
  Cleaning 
n (%)j 
X ( X.X) 
  Sexual pleasure 
n (%)j 
X ( X.X) 
  Insert a product for the management of menses 
n (%)j 
X ( X.X) 
  Other 
n (%)j 
X ( X.X) 
 
 
 
Programmers Notes:  
- Please add in ‘Chose not to answer’ where applicable 
- Please repeat the table for all available Trial Months 
 
 
Percentages are calculated out of the number of participants a In the safety population b Left rings at the research centre c With main partner d Took rings  
e Used a condom f Had anal sex since last visit g Had a menstrual bleeding/spotting since last visit h Had ring expelled/removed since last visit  
i Cleaned ring before reinsertion j Inserted fingers into vagina


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.9 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
Trial Month X 
 
Page 80 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Decision on extra rings, during three monthly visits 
 
 
  Always took them 
n (%)a 
X ( X.X) 
  Always left them at the research centre to collect monthly 
n (%)a 
X ( X.X) 
  Sometimes took them, sometimes left them at the research centre 
n (%)a 
X ( X.X) 
    Initially leave them at the research centre then later start taking them 
n (%)b 
X ( X.X) 
    Initially take them, then start leaving them at the research centre 
n (%)b 
X ( X.X) 
    It varied 
n (%)b 
X ( X.X) 
 
 
 
Reasons for leaving the rings at research centre  
 
 
  Did not want anyone to see the rings 
n (%)c 
X ( X.X) 
  Did not have a private place to keep the unused rings at home 
n (%)c 
X ( X.X) 
  Did not have a private place to keep the used rings at home 
n (%)c 
X ( X.X) 
  Did not have an appropriate storage place to keep the rings (used/unused) at home 
n (%)c 
X ( X.X) 
  Did not have a private place to insert the rings at home 
n (%)c 
X ( X.X) 
  Worried I might lose the ring(s)  
n (%)c 
X ( X.X) 
  Felt I might forget to insert a new ring if I don’t come each month 
n (%)c 
X ( X.X) 
  Liked coming to the research centre for HIV tests each month 
n (%)c 
X ( X.X) 
  Liked coming to the research centre monthly for social reasons 
n (%)c 
X ( X.X) 
  Other 
n (%)c 
X ( X.X) 
 
 
 
Main partner knowledge of the vaginal ring and study participation 
 
 
  He knows about the study and the ring 
n (%)d 
X ( X.X) 
  He only knows that I am in a study 
n (%)d 
X ( X.X) 
  He only knows that I am wearing a ring 
n (%)d 
X ( X.X) 
  He doesn’t know about the study or the ring 
n (%)d 
X ( X.X) 
  Don’t know 
n (%)d 
X ( X.X) 
 
 
 
Programmers Note: Please add in ‘Chose not to answer’ where applicable 
 
 
Percentages are calculated out of the number of participants a In the safety population b Sometimes took/sometimes left the rings  c Left rings at the research centre 
d With main partner e Took rings f Used a condom g Had anal sex since last visit h Had a menstrual bleeding/spotting since last visit  
i Had ring expelled/removed since last visit j  Cleaned ring before reinsertion k Inserted fingers into vagina 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.9 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
Trial Month X 
 
Page 81 of 93 
 
Version 1.0 
26 Mar 2020 
 
Percentages are calculated out of the number of participants a In the safety population b Sometimes took/sometimes left the rings  c Left rings at the research centre 
d With main partner e Took rings f Used a condom g Had anal sex since last visit h Had a menstrual bleeding/spotting since last visit  
i Had ring expelled/removed since last visit j  Cleaned ring before reinsertion k Inserted fingers into vagina  
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
View on the information sheet 
 
 
  The sheet is good as it is 
n (%)a 
X ( X.X) 
  The sheet is hard to understand 
n (%)a 
X ( X.X) 
  The sheet needs more information 
n (%)a 
X ( X.X) 
  The sheet needs to be changed 
n (%)a 
X ( X.X) 
  Did not read the instruction sheet 
n (%)a 
X ( X.X) 
  Can’t remember (the instruction sheet) 
n (%)a 
X ( X.X) 
 
 
 
Over the duration of the study, was it easy or difficult to remove your ring? 
 
 
  Easy to remove 
n (%)a 
X ( X.X) 
  Difficult to remove 
n (%)a 
X ( X.X) 
  Sometimes easy, sometimes difficult to remove 
n (%)a 
X ( X.X) 
  Got easier to remove over time with practice 
n (%)a 
X ( X.X) 
  Neither easy nor difficult to remove 
n (%)a 
X ( X.X) 
 
 
 
Over the duration of the study, was it easy or difficult to insert a new ring? 
 
 
  Easy to insert 
n (%)a 
X ( X.X) 
  Difficult to insert 
n (%)a 
X ( X.X) 
  Sometimes easy, sometimes difficult to insert 
n (%)a 
X ( X.X) 
  Got easier to insert over time with practice 
n (%)a 
X ( X.X) 
  Neither easy nor difficult to insert 
n (%)a 
X ( X.X) 
 
 
 
Programmers Note: Please add in ‘Chose not to answer’ where applicable   


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.9 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
Trial Month X 
 
Page 82 of 93 
 
Version 1.0 
26 Mar 2020 
 
Percentages are calculated out of the number of participants a In the safety population b Sometimes took/sometimes left the rings  c Left rings at the research centre 
d With main partner e Took rings f Used a condom g Had anal sex since last visit h Had a menstrual bleeding/spotting since last visit  
i Had ring expelled/removed since last visit j  Cleaned ring before reinsertion k Inserted fingers into vagina 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Experience with the bag given to put the used rings in 
 
 
  The bag was easy to open and close 
n (%)a 
X ( X.X) 
  The bag was hard to open and close 
n (%)a 
X ( X.X) 
  The bag was sometimes lost 
n (%)a 
X ( X.X) 
  The bag was sometimes used for something else 
n (%)a 
X ( X.X) 
  The bag was fine 
n (%)a 
X ( X.X) 
  I did not like having to keep the empty bag(s) 
n (%)a 
X ( X.X) 
  I did not like having the used ring(s) in the house 
n (%)a 
X ( X.X) 
  I did not like carrying the used ring(s) to the research centre 
n (%)a 
X ( X.X) 
  Someone found the ring bag(s) (with or without rings), 
n (%)a 
X ( X.X) 
  I did not like the look of the bag 
n (%)a 
X ( X.X) 
  It was difficult to bring the bags back to the clinic 
n (%)a 
X ( X.X) 
  Other 
n (%)a 
X ( X.X) 
  Not applicable, I did not use the bags or return a ring since the last visit 
n (%)a 
X ( X.X) 
 
 
 
Place of storage of the unused ring(s) before insertion 
n (%)e 
X ( X.X) 
  In bag/handbag 
n (%)e 
X ( X.X) 
  In a shared cupboard/drawer in the house 
n (%)e 
X ( X.X) 
  In a personal cupboard/drawer in my room/in the house 
n (%)e 
X ( X.X) 
  In a locked place that no-one else could access 
n (%)e 
X ( X.X) 
  At someone else’s house 
n (%)e 
X ( X.X) 
  Other 
n (%)e 
X ( X.X) 
  Not applicable, I did not ever take any extra unused rings home 
n (%)e 
X ( X.X) 
 
 
 
Programmers Note: Please add in ‘Chose not to answer’ where applicable 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.9 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
Trial Month X 
 
Page 83 of 93 
 
Version 1.0 
26 Mar 2020 
 
Percentages are calculated out of the number of participants a In the safety population b Sometimes took/sometimes left the rings  c Left rings at the research centre 
d With main partner e Took rings f Used a condom g Had anal sex since last visit h Had a menstrual bleeding/spotting since last visit  
i Had ring expelled/removed since last visit j  Cleaned ring before reinsertion k Inserted fingers into vagina 
 
Statistic 
IPM 032 Overall 
(N=XXX) 
 
 
 
Experience when storing the unused ring(s) 
 
 
  There were no problems storing the unused ring(s) 
n (%)e 
X ( X.X) 
  I was concerned that someone might find the unused ring 
n (%)e 
X ( X.X) 
  I sometimes forgot where I had stored the unused ring(s)/lost the unused ring(s) 
n (%)e 
X ( X.X) 
  The ring(s) accidentally got thrown away 
n (%)e 
X ( X.X) 
  I did not like storing the unused rings 
n (%)e 
X ( X.X) 
  Someone found the ring(s) and that was problematic 
n (%)e 
X ( X.X) 
  Someone found the ring(s) but it was not problematic 
n (%)e 
X ( X.X) 
  Other 
n (%)e 
X ( X.X) 
  Not applicable, I did not ever take any extra unused rings home 
n (%)e 
X ( X.X) 
 
 
 
Place of storage of the used ring(s) after removal 
 
 
  I returned the used ring(s) to the research centre straight away 
n (%)a 
X ( X.X) 
  In a bag/handbag 
n (%)a 
X ( X.X) 
  In a shared cupboard/drawer in the house 
n (%)a 
X ( X.X) 
  In a personal cupboard/drawer in my room/in the house 
n (%)a 
X ( X.X) 
  In a locked place that no-one else could access 
n (%)a 
X ( X.X) 
  At someone else’s house 
n (%)a 
X ( X.X) 
  Other 
n (%)a 
X ( X.X) 
  Not applicable, I did not store any extra used rings since the last visit 
n (%)a 
X ( X.X) 
 
 
 
Experience when storing the used ring 
 
 
  There were no problems storing the used ring 
n (%)a 
X ( X.X) 
  I was concerned that someone might find the used ring 
n (%)a 
X ( X.X) 
  I sometimes forgot where I had stored the used ring(s)/lost the used ring(s) 
n (%)a 
X ( X.X) 
  The ring accidentally got thrown away 
n (%)a 
X ( X.X) 
  I did not like storing the used rings 
n (%)a 
X ( X.X) 
  Someone found the ring(s) and that was problematic 
n (%)a 
X ( X.X) 
  Someone found the ring(s) but it was not problematic 
n (%)a 
X ( X.X) 
  Other 
n (%)a 
X ( X.X) 
  Not applicable, I did not ever have/store any extra used rings at home 
n (%)a 
X ( X.X) 
Programmers Note: Please add in ‘Chose not to answer’ where applicable 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.9 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
Trial Month X 
 
Page 84 of 93 
 
Version 1.0 
26 Mar 2020 
 
Percentages are calculated out of the number of participants a In the safety population b Sometimes took/sometimes left the rings  c Left rings at the research centre 
d With main partner e Took rings f Used a condom g Had anal sex since last visit h Had a menstrual bleeding/spotting since last visit  
i Had ring expelled/removed since last visit j  Cleaned ring before reinsertion k Inserted fingers into vagina 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Blood sample preferences 
 
 
  It is fine to have a blood sample taken at every visit 
n (%)a 
X ( X.X) 
  Prefer to have blood sample taken less often 
n (%)a 
X ( X.X) 
 
 
 
Vaginal fluid sample preferences 
 
 
  It is fine to have a vaginal fluid sample taken at every visit 
n (%)a 
X ( X.X) 
  Prefer to have vaginal fluid sample taken less often 
n (%)a 
X ( X.X) 
 
 
 
Experienced any of the following in the study 
 
 
  In general, the length of time spent at the research centre for the study visits was too long 
n (%)a 
X ( X.X) 
  In general, the length of time spent at the research centre to pick up rings was too long 
n (%)a 
X ( X.X) 
  Transport to the research centre for scheduled visits was a problem 
n (%)a 
X ( X.X) 
  I was treated well when coming to the research centre for regular visits 
n (%)a 
X ( X.X) 
  I was treated well when I came to the research centre to pick up rings 
n (%)a 
X ( X.X) 
  Transport to pick up rings was a problem 
n (%)a 
X ( X.X) 
  Partner is happy about participation (if he is aware of participation) 
n (%)a 
X ( X.X) 
  My neighbors, family, or friends know about my participation in this study 
n (%)a 
X ( X.X) 
  My neighbors, family, or friends (as above) are happy about my participation in this study (if they are aware of participation) 
n (%)a 
X ( X.X) 
  Other 
n (%)a 
X ( X.X) 
 
 
 
Participant experience of study 
 
 
  Participant really didn’t like participating in this study 
n (%)a 
X ( X.X) 
  Participating in this study was alright/okay 
n (%)a 
X ( X.X) 
  Participant really liked participating in this study 
n (%)a 
X ( X.X) 
  Other 
n (%)a 
X ( X.X) 
 
 
 
Programmers Note: Please add in ‘Chose not to answer’ where applicable 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.9 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
Trial Month X 
 
Page 85 of 93 
 
Version 1.0 
26 Mar 2020 
 
Percentages are calculated out of the number of participants a In the safety population b Sometimes took/sometimes left the rings  c Left rings at the research centre 
d With main partner e Took rings f Used a condom g Had anal sex since last visit h Had a menstrual bleeding/spotting since last visit  
i Had ring expelled/removed since last visit j  Cleaned ring before reinsertion k Inserted fingers into vagina 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Preference if not in the DREAM study: Prefer to come to the health care clinic/provider for new rings each month or every three months 
 
 
  Each month 
n (%)a 
X ( X.X) 
  Every three months 
n (%)a 
X ( X.X) 
  Don’t mind 
n (%)a 
X ( X.X) 
  Depends 
n (%)a 
X ( X.X) 
 
 
 
Preference if not in the DREAM study: Prefer to come to the health care clinic/provider for HIV tests each month or every three months 
 
 
  Each month 
n (%)a 
X ( X.X) 
  Every three months 
n (%)a 
X ( X.X) 
  Don’t mind 
n (%)a 
X ( X.X) 
  Depends 
n (%)a 
X ( X.X) 
 
 
 
Currently have a main sex partner 
 
 
  Yes 
n (%)a 
X ( X.X) 
  No 
n (%)a 
X ( X.X) 
 
 
 
Currently live with main partner 
 
 
  Yes 
n (%)d 
X ( X.X) 
  No 
n (%)d 
X ( X.X) 
 
 
 
Other partners since last scheduled visit 
 
 
  0 – 1 
n (%)a 
X ( X.X) 
  >= 2 
n (%)a 
X ( X.X) 
 
 
 
Number of sex acts over the past month 
Mean 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
 
(Min, Max) 
(XX, XX) 
 
 
 
Programmers Note: Please add in ‘Chose not to answer’ where applicable 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.9 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
Trial Month X 
 
Page 86 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Use of a male condom over the past month 
 
 
  Always 
n (%)a 
X ( X.X) 
  Sometimes 
n (%)a 
X ( X.X) 
  Often 
n (%)a 
X ( X.X) 
  Never 
n (%)a 
X ( X.X) 
 
 
 
Use of a female condom over the past month 
 
 
  Always 
n (%)a 
X ( X.X) 
  Sometimes 
n (%)a 
X ( X.X) 
  Often 
n (%)a 
X ( X.X) 
  Never 
n (%)a 
X ( X.X) 
 
 
 
Used a condom during last round of vaginal sex 
 
 
  No 
n (%)a 
X ( X.X) 
  Yes 
n (%)a 
X ( X.X) 
    Male condom 
n (%)f 
X ( X.X) 
    Female condom 
n (%)f 
X ( X.X) 
 
 
 
Had anal sex since last scheduled visit 
 
 
  No 
n (%)a 
X ( X.X) 
  Yes 
n (%)a 
X ( X.X) 
     Used a condom 
n (%)g 
X ( X.X) 
     Did not use a condom 
n (%)g 
X ( X.X) 
 
 
 
Had menstrual bleeding/spotting since last scheduled visit 
 
 
  Yes 
n (%)a 
X ( X.X) 
  No 
n (%)a 
X ( X.X) 
 
 
 
Programmers Note: Please add in ‘Chose not to answer’ where applicable 
 
 
Percentages are calculated out of the number of participants a In the safety population b Sometimes took/sometimes left the rings  c Left rings at the research centre 
d With main partner e Took rings f Used a condom g Had anal sex since last visit h Had a menstrual bleeding/spotting since last visit  
i Had ring expelled/removed since last visit j  Cleaned ring before reinsertion k Inserted fingers into vagina  


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.9 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
Trial Month X 
 
Page 87 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Products used in the past 3 months to control menstrual bleeding/spotting 
 
 
  Tissue, toilet paper, paper, cloth or cotton wool put inside the vagina 
n (%)h 
X ( X.X) 
  Tissue, toilet paper, paper, cloth or cotton wool put inside the underwear/clothing 
n (%)h 
X ( X.X) 
  Tampon 
n (%)h 
X ( X.X) 
  Sanitary pad 
n (%)h 
X ( X.X) 
  Menstrual cup 
n (%)h 
X ( X.X) 
  Water without soap (inside the vagina) 
n (%)h 
X ( X.X) 
  Water with soap (inside the vagina) 
n (%)h 
X ( X.X) 
  Nothing was used 
n (%)h 
X ( X.X) 
  Other 
n (%)h 
X ( X.X) 
 
 
 
Ring removed/expelled since last scheduled visit? 
 
 
  Yes 
n (%)a 
X ( X.X) 
  No 
n (%)a 
X ( X.X) 
 
 
 
Reason why the ring was removed/expelled 
 
 
  Took it out because it was uncomfortable/painful 
n (%)i 
X ( X.X) 
  Took it out to clean the ring 
n (%)i 
X ( X.X) 
  Took it out because on menses 
n (%)i 
X ( X.X) 
  Took it out because of real/perceived side effects 
n (%)i 
X ( X.X) 
  Took it out because partner requested it 
n (%)i 
X ( X.X) 
  Took it out for sex 
n (%)i 
X ( X.X) 
  Took it out so that partner did not find out about it 
n (%)i 
X ( X.X) 
  Accidentally came out 
n (%)i 
X ( X.X) 
  Other 
n (%)i 
X ( X.X) 
 
 
 
When the ring was removed/expelled did you clean the ring before reinsertion? 
 
 
  Yes 
n (%)i 
X ( X.X) 
  No 
n (%)i 
X ( X.X) 
 
 
 
Programmers Note: Please add in ‘Chose not to answer’ where applicable 
 
 
Percentages are calculated out of the number of participants a In the safety population b Sometimes took/sometimes left the rings  c Left rings at the research centre 
d With main partner e Took rings f Used a condom g Had anal sex since last visit h Had a menstrual bleeding/spotting since last visit  
i Had ring expelled/removed since last visit j  Cleaned ring before reinsertion k Inserted fingers into vagina  
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.9 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
Trial Month X 
 
Page 88 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
What did you use to clean the ring when it was removed/expelled? 
 
 
  Water only 
n (%)j 
X ( X.X) 
  Soap only 
n (%)j 
X ( X.X) 
  Water and soap 
n (%)j 
X ( X.X) 
  Disinfectant 
n (%)j 
X ( X.X) 
  Water and soap 
n (%)j 
X ( X.X) 
  Disinfectant 
n (%)j 
X ( X.X) 
  Herbal products 
n (%)j 
X ( X.X) 
  Traditional medicine 
n (%)j 
X ( X.X) 
  Bubble bath 
n (%)j 
X ( X.X) 
  Bath salts 
n (%)j 
X ( X.X) 
  Dishwashing liquid 
n (%)j 
X ( X.X) 
  Other 
n (%)j 
X ( X.X) 
 
 
 
Level of being worried about getting infected with HIV in the next year 
 
 
  Very worried 
n (%)a 
X ( X.X) 
  A little worried 
n (%)a 
X ( X.X) 
  Not worried at all 
n (%)a 
X ( X.X) 
 
 
 
Inserted fingers into vagina since last schedule visit 
 
 
  Yes 
n (%)a 
X ( X.X) 
  No 
n (%)a 
X ( X.X) 
 
 
 
Reason for inserting fingers into vagina 
n (%)k 
X ( X.X) 
  Check the position of the ring 
n (%)k 
X ( X.X) 
  Insert/remove the ring 
n (%)k 
X ( X.X) 
  Cleaning 
n (%)k 
X ( X.X) 
  Sexual pleasure 
n (%)k 
X ( X.X) 
  Insert a product for the management of menses 
n (%)k 
X ( X.X) 
  Other 
n (%)k 
X ( X.X) 
 
 
 
Programmers Note: Please add in ‘Chose not to answer’ where applicable 
 
 
Percentages are calculated out of the number of participants a In the safety population b Sometimes took/sometimes left the rings  c Left rings at the research centre 
d With main partner e Took rings f Used a condom g Had anal sex since last visit h Had a menstrual bleeding/spotting since last visit  
i Had ring expelled/removed since last visit j  Cleaned ring before reinsertion k Inserted fingers into vagina  


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.9 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
Trial Month X 
 
Page 89 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Participant views on are the following good ways to ensure ring use: Adherence 
 
 
Test blood to see how much medicine is in the blood 
 
 
   Yes 
n (%)a 
X ( X.X) 
   No 
n (%)a 
X ( X.X) 
Test used ring to see how much medicine is still in the ring 
 
 
   Yes 
n (%)a 
X ( X.X) 
   No 
n (%)a 
X ( X.X) 
Ask the woman if she has been using the ring 
 
 
   Yes 
n (%)a 
X ( X.X) 
   No 
n (%)a 
X ( X.X) 
Other 
 
 
   Yes 
n (%)a 
X ( X.X) 
   No 
n (%)a 
X ( X.X) 
 
 
 
Would more women use the ring properly if they knew the blood tests/used rings would show staff who was using the ring as intended  
 
 
and who was not? 
 
 
  Yes 
n (%)a 
X ( X.X) 
  No 
n (%)a 
X ( X.X) 
  Don’t know 
n (%)a 
X ( X.X) 
 
 
 
Is it possible for women to use the ring as requested? 
 
 
  Yes 
n (%)a 
X ( X.X) 
  No 
n (%)a 
X ( X.X) 
  Don’t know 
n (%)a 
X ( X.X) 
 
 
 
Programmers Note: Please add in ‘Chose not to answer’ where applicable 
 
 
Percentages are calculated out of the number of participants a In the safety population b Sometimes took/sometimes left the rings  c Left rings at the research centre 
d With main partner e Took rings f Used a condom g Had anal sex since last visit h Had a menstrual bleeding/spotting since last visit  
i Had ring expelled/removed since last visit j  Cleaned ring before reinsertion k Inserted fingers into vagina  


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.9 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
Trial Month X 
 
Page 90 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Most likely reason(s) for women to remove the ring 
n (%)a 
X ( X.X) 
  Partner request 
n (%)a 
X ( X.X) 
  Fear of partner feeling it 
n (%)a 
X ( X.X) 
  Influence of others (not partner) 
n (%)a 
X ( X.X) 
  Wants a break from having the ring inside 
n (%)a 
X ( X.X) 
  Menses 
n (%)a 
X ( X.X) 
  Side effects 
n (%)a 
X ( X.X) 
  Discomfort/pain 
n (%)a 
X ( X.X) 
  Belief that ring doesn’t work 
n (%)a 
X ( X.X) 
  Other 
n (%)a 
X ( X.X) 
 
 
 
All women can use the ring without taking it out 
 
 
  Strongly agree 
n (%)a 
X ( X.X) 
  Somewhat agree 
n (%)a 
X ( X.X) 
  Strongly disagree 
n (%)a 
X ( X.X) 
 
 
 
Women would need a break from using the ring every few months 
 
 
  Strongly agree 
n (%)a 
X ( X.X) 
  Somewhat agree 
n (%)a 
X ( X.X) 
  Strongly disagree 
n (%)a 
X ( X.X) 
 
 
 
Would women in the community want to wear the ring if it were available? 
 
 
  Yes 
n (%)a 
X ( X.X) 
  No 
n (%)a 
X ( X.X) 
 
 
 
If the ring is made available to the public, where would most women want to get it from? 
 
 
  A clinic 
n (%)a 
X ( X.X) 
  Pharmacy 
n (%)a 
X ( X.X) 
  Private doctor 
n (%)a 
X ( X.X) 
  Other 
n (%)a 
X ( X.X) 
  They wouldn’t want to use it 
n (%)a 
X ( X.X) 
Programmers Note: Please add in ‘Chose not to answer’ where applicable 
 
 
Percentages are calculated out of the number of participants a In the safety population b Sometimes took/sometimes left the rings  c Left rings at the research centre 
d With main partner e Took rings f Used a condom g Had anal sex since last visit h Had a menstrual bleeding/spotting since last visit  
i Had ring expelled/removed since last visit j  Cleaned ring before reinsertion k Inserted fingers into vagina 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.9 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
Trial Month X 
 
Page 91 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Statistic 
IPM 032 Overall 
 
 
(N=XXX) 
 
 
 
Willingness to pay for the ring, if it was to be made available to the public 
 
 
  It should be free 
n (%)a 
X ( X.X) 
  Would pay 
n (%)a 
X ( X.X) 
 
 
 
Spend South African Rand on ring 
Mean 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
 
(Min, Max) 
(XX, XX) 
 
 
 
Spend Ugandan Shilling on ring 
Mean 
XX.X 
 
(q1,med,q3) 
(XX.X,XX.X,XX.X) 
 
SD 
XX.XX 
 
(Min, Max) 
(XX, XX) 
 
 
 
Where should the ring be marketed/advertised if it was to be made available to the public? 
 
 
  By qualified healthcare providers 
n (%)a 
X ( X.X) 
  The local clinic/hospital notice boards 
n (%)a 
X ( X.X) 
  Pamphlets in clinics only 
n (%)a 
X ( X.X) 
  Pamphlets in pharmacies/private doctor 
n (%)a 
X ( X.X) 
  Pamphlets in public places 
n (%)a 
X ( X.X) 
  Television and/or radio 
n (%)a 
X ( X.X) 
  Billboards 
n (%)a 
X ( X.X) 
  Other place 
n (%)a 
X ( X.X) 
 
 
 
Programmers Note: Please add in ‘Chose not to answer’ where applicable 
 
 
Percentages are calculated out of the number of participants a In the safety population b Sometimes took/sometimes left the rings  c Left rings at the research centre 
d With main partner e Took rings f Used a condom g Had anal sex since last visit h Had a menstrual bleeding/spotting since last visit  
i Had ring expelled/removed since last visit j  Cleaned ring before reinsertion k Inserted fingers into vagina  
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.10 
Participant Questionnaire – Vaginal Practices 
Safety Population 
Trial Month X 
 
Page 92 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Applied using 
 
Removed Ring? 
 
Reason for using product 
Product Used 
Hands 
Cloth 
Other 
 
No 
Yes 
 
General 
Clean 
Clean 
Clean 
… 
Other 
 
 
 
 
 
 
 
 
Cleaning 
During 
Before 
After 
 
 
 
 
 
 
 
 
 
 
 
Menses 
Sex 
Sex 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
External cleaning 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Water only 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Soap only 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Soap and Water 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Disinfectant/ 
 
 
 
 
 
 
 
 
 
 
 
 
 
  detergent 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Traditional 
 
 
 
 
 
 
 
 
 
 
 
 
 
  products 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Other 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Internal cleaning 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Water only 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Soap only 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Soap and Water 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Disinfectant/ 
 
 
 
 
 
 
 
 
 
 
 
 
 
  detergent 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Traditional 
 
 
 
 
 
 
 
 
 
 
 
 
 
  products 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Gels 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Other 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaginal steaming 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Traditional 
 
 
 
 
 
 
 
 
 
 
 
 
 
  products 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Commercial 
 
 
 
 
 
 
 
 
 
 
 
 
 
  products 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Other 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmmers Note: Please repeat the table for all available Trial Months 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Percentages are calculated out of the number of participants in the safety population  
 


 TABLE SHELLS                                                                                                                                                                                      
 
 
IPM 032 
 
 
 
Table 14.6.10 
Participant Questionnaire – Vaginal Practices 
Safety Population 
Trial Month X 
 
Page 93 of 93 
 
Version 1.0 
26 Mar 2020 
 
 
Applied using 
 
Removed Ring? 
 
Reason for using product 
Product Used 
Hands 
Cloth 
Other 
 
No 
Yes 
 
General 
Clean 
Clean 
Clean 
 
Other 
 
 
 
 
 
 
 
 
Cleaning 
During 
Before 
After 
 
 
 
 
 
 
 
 
 
 
 
Menses 
Sex 
Sex 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inserted into vagina 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Tampon 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Cloth 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Paper 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Cotton wool 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Snuff/Kuber 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Zambuk 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Talc 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Other commercial 
 
 
 
 
 
 
 
 
 
 
 
 
 
  products 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Traditional  
 
 
 
 
 
 
 
 
 
 
 
 
 
  products 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Other 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
External application 
 
 
 
 
 
 
 
 
 
 
 
 
 
of products 
 
 
 
 
 
 
 
 
 
 
 
 
 
  Commercial 
 
 
 
 
 
 
 
 
 
 
 
 
 
  cream 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Talc 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Intimate sprays 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Traditional 
 
 
 
 
 
 
 
 
 
 
 
 
 
  products 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
  Other 
X (X.X) 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
 
X (X.X) 
X (X.X) 
X (X.X) 
X (X.X) 
… 
X (X.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmmers Note: Please repeat the table for all available Trial Months 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Percentages are calculated out of the number of participants in the safety population  
 


 LISTING SHELLS                                                                         
IPM 032 
 
Page 1 of 12 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
IPM 032 
 
 
 
 
FIGURE SHELLS – VERSION 1.0, 26 MAR 2020 


 LISTING SHELLS                                                                         
IPM 032 
 
Page 2 of 12 
Version 1.0 
26 Mar 2020 
 
Number 
Listing Heading 
14.1 
Demographics 
14.1.1.1 
Disposition of Participants 
14.1.1.1.1 
Time to Trial Discontinuation  
14.1.1.1.2 
Time to (Premature) Permanent Investigational Product Discontinuation  
14.3 
Safety Data 
14.3.5.1 
Adherence – Dapivirine Residual Levels in Used Rings 
14.3.5.1.1 
Dapivirine Ring Residual Levels (mg) 
14.3.5.1.2 
Dapivirine Ring Residual Levels (mg) By Trial Visit and Category of Residual 
Amount  
14.3.5.1.3 
Relating The Dapivirine Ring Residual Levels (mg) To The Time Intervals Between 
Consecutive Ring Replacements  
14.3.5.1.4 
Residual Levels of Dapivirine (mg) in The Last Three Returned Rings Prior To HIV 
Seroconversion VS Average Ring Residual Levels 
14.3.5.1.8 
Corrected Residual Levels of Dapivirine in The Last Three Returned Rings Prior To 
HIV Seroconversion VS Average Ring Residual Levels of HIV- Participants 
14.3.7 
Other Safety Data 
14.3.7.7 
Time to HIV-1 Seroconversion – m-ITT population  
14.3.7.8 
Time to HIV-1 Seroconversion – PP population 
14.6 
Other Data 
14.6.4 
Correlation Between Dapivirine Residual Amounts (mg) in Returned Used Vaginal 
Rings and Results From Visual Inspection of Returned Vaginal Rings  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Figure 14.1.1.1.1 
Kaplan-Meier Curves, Time to Trial Discontinuity 
Safety Population 
 
 
Page 3 of 12 
Version 1.0 
 
26 Mar 2020 
 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Figure 14.1.1.1.2 
Kaplan-Meier Curves, Time to (Premature) Permanent Investigational Product Discontinuation 
Safety Population 
 
 
Page 4 of 12 
Version 1.0 
 
26 Mar 2020 
 
 
Programmers Note: Figure wil resemble F14.1.1.1 with time to permanent IP data. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Figure 14.3.5.1.1 
Dapivirine Ring Residual Levels (mg) 
Safety Population 
 
 
Page 5 of 12 
Version 1.0 
 
26 Mar 2020 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please repeat for all centres. 
 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Figure 14.3.5.1.2 
Dapivirine Ring Residual Levels (mg) By Trial Visit and Category of Residual Amount   
Safety Population 
 
 
Page 6 of 12 
Version 1.0 
 
26 Mar 2020 
 
 
Programmers Note: Please repeat for all  trial months.


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Figure 14.3.5.1.3 
Relating The Dapivirine Ring Residual Levels (mg) To The Time Intervals Between Consecutive Ring Replacements 
Safety Population 
 
 
Page 7 of 12 
Version 1.0 
 
26 Mar 2020 
 
 
Programmers Note: Please repeat for all centres. 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Figure 14.3.5.1.4 
Residual Levels of Dapivirine (mg) in The Last Three Returned Rings Prior To HIV Seroconversion VS Average Ring Residual Levels  
Safety Population 
 
 
Page 8 of 12 
Version 1.0 
 
26 Mar 2020 
 
 
 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Figure 14.3.5.1.5 
Residual Levels of Dapivirine (mg) in The Last Two Returned Rings Prior To HIV Seroconversion VS Average Ring Residual Levels  
Safety Population 
 
 
Page 9 of 12 
Version 1.0 
 
26 Mar 2020 
 
 
Programmers Note: Figure wil resemble F14.5.1.4 using data from last two rings of those who seroconverted. 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Figure 14.3.7.7 
Time to HIV-1 Seoconversion 
m-ITT Population 
 
 
Page 10 of 12 
Version 1.0 
 
26 Mar 2020 
 
 
Programmers Note: Figure wil resemble F14.1.1.1. 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Figure 14.3.7.8 
Time to HIV-1 Seroconversion 
PP Population 
 
 
Page 11 of 12 
Version 1.0 
 
26 Mar 2020 
 
Programmers Note: Figure wil resemble F14.1.1.1. 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Figure 14.6.4 
Correlation Between Dapivirine Residual Leverl (mg) in Returned Used Vaginal Rings and Results From Visual Inspection of Returned  
Vaginal Rings 
Safety Population 
 
 
Page 12 of 12 
Version 1.0 
 
26 Mar 2020 
 
 


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IPM 032 
 
 
 
 
LIST OF PARTICIPANT LISTINGS – VERSION 1.0, 26 MAR 2020 


Number 
Listing Heading 
16.2.1 
Discontinued Participants 
16.2.1.1 
Enrollment 
16.2.1.2 
Screen Failures 
16.2.1.3 
Participant Disposition: Participant Visits 
16.2.1.4 
Missed Visits 
16.2.2 
Protocol Deviations 
16.2.2.1  
Protocol Deviations 
16.2.3 
Participants Excluded from Efficacy Analysis 
16.2.3.1 
Analysis Populations 
16.2.4 
Demographic Data 
16.2.4.1 
Demographics at Screening  
16.2.4.2 
Demographics at Screening  
16.2.4.3 
Medical History at Screening 
16.2.4.4 
Contraceptive/ Menstrual/ Obstetric History at Screening 
16.2.4.5 
Gynaecological History at Screening 
16.2.4.6 
Prior Medication 
16.2.4.7 
Concomitant Medication 
16.2.5 
Compliance and/ or Drug Concentration Data 
16.2.5.1 
Adherence to Investigational Product 
16.2.5.2 
Self-Reported Acceptability and Adherence to Investigational Product  
16.2.5.3 
Returned Ring Log 
16.2.5.4 
Ring Insertion/ Removal 
16.2.5.5 
Accidental Expulsion/ Removal 
16.2.5.6 
Participant Questionnaire – Part A (Month 1, 2 and 3) 
16.2.5.7 
Participant Questionnaire – Part B (Month 2 and 3 Only) 
16.2.5.8 
Participant Questionnaire – Part C (Month 1, 2 and 3) 
16.2.5.9 
Participant Questionnaire – 3 Month Follow-up 
16.2.5.10 
Participant Questionnaire – LPUV 
16.2.5.11 
Feasibility of a 3-Monthly Clinical Follow-Up Schedule 
16.2.5.12 
Participant Questionnaire – Vaginal Practices 
16.2.5.13 
Dapivirine Concentration Sample Collection 
16.2.5.14 
Dapivirine Concentration in the Last Three Returned Rings Prior to HIV-1 
Seroconversion 
16.2.5.15 
Dapivirine Concentration in the Last Two Returned Rings Prior to First Positive HIV 
RNA PCR Test 
16.2.6 
Individual Efficacy Response Data 
16.2.7 
Adverse Events Listings 
16.2.7.1 
Treatment Emergent Adverse Events 
16.2.7.2 
Product-Related Treatment Emergent Adverse Events 
16.2.7.3 
Treatment Emergent Adverse Events Leading to Temporary Product 
Discontinuation 
16.2.7.4 
Treatment Emergent Adverse Events Leading to Permanent Product 
Discontinuation 
16.2.7.5 
Treatment Emergent Adverse Events Leading to Premature Trial Discontinuation 
16.2.7.6 
Serious Treatment Emergent Adverse Events 
16.2.7.7 
Grade 3 or 4 Treatment Emergent Adverse Events 
16.2.7.8 
Treatment Emergent Adverse Events Leading to Death 


Number 
Listing Heading 
16.2.7.9 
Urogenital Treatment Emergent Adverse Events 
16.2.7.10 
Social Harms Reported as Treatment Emergent Adverse Events 
16.2.7.11 
Non-Treatment Emergent Adverse Events 
16.2.8 
Listings of Individual Laboratory Measurements and Other Safety Data 
16.2.8.1 
Haematology Results 
16.2.8.2 
Biochemistry Results 
16.2.8.3 
Urinalysis and Microscopy Results 
16.2.8.4 
Abnormal Clinical Laboratory Data 
16.2.8.5 
Vital Signs 
16.2.8.6 
Physical Examination 
16.2.8.7 
Menses Information and Pregnancy Test Results 
16.2.8.8 
Sexually Transmitted Infections 
16.2.8.9 
HIV-1 Seroconversion 
16.2.8.10 
HIV-1 Seroconversion: Genotype Testing 
16.2.8.11 
HIV-1 Seroconversion on Investigational Product 
16.2.8.12 
Participants with Drug Resistance Mutations 
16.2.8.13 
HIV-1 NNRTI Drug Susceptibility: Stanford Interpretation of Genotype 
16.2.8.14 
Population-Based Sequencing: Mutations per Region 
16.2.8.15 
Population-Based Genotyping Amongst Participants who HIV-1 Seroconverted 
16.2.8.16 
Pelvic/ Speculum Examinations 
16.2.8.17 
Cervical Cytology Results 
16.2.8.18.1 
Social Harms Report 
16.2.8.18.2 
Social Harms Follow-up Report 
16.2.8.19 
Timing Profile 
16.2.9 
PK Listings 
16.2.10 
PD Listings 
 
 
 
 
 
 
 
 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
Listing 16.2.1.1 
Enrollment 
Safety Population 
 
 
Page 4 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Date of Signed 
Consent Version 
Met All INCL 
Met No EXCL  
  Participant ID 
Schedule 
Consent 
No. and Date 
Criteria 
Criteria 
 
 
 
 
 
 
Centre XXX 
 
 
 
 
 
   XXXXXXXX 
A / 
ddMMMyyyy 
XX-ddMMMyyyy 
Yes / 
Yes / 
 
B / 
 
 
No 
No  
 
C  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes:  
- Populate IPM027 Exit Date with whichever is later, LPUV or Exit Visit. 
- Please note that the incl/excl criteria is that of the DVR-naïve cohort; see p.12/13 of the protocol for the incl/excl criteria of the participants who were previously exposed to 
the DVR 
 
 
 
 
 
 
AE = Adverse event; EXCL = Exclusion criteria; INCL = Inclusion criteria; LPUV = Last product use visit 
Visit Schedule A = Participants attended trial month visit 1, 4, 7, 10, 13 and 16/Exit 
Visit Schedule B = Participants attended trial month visit 1, 2, 5, 8, 11, 14 and 17/Exit 
Visit Schedule C = Participants attended trial month visit 1, 2, 3, 6, 9, 12 and 15/Exit 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
Listing 16.2.1.1 
Enrollment 
Safety Population 
 
 
Page 5 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
INCL No. Not Met 
EXCL No. Met 
  Participant ID 
Schedule 
 
 
 
 
 
 
Centre XX 
 
 
 
   XXXXXXXX 
A / 
1. Previously enrolled in the IPM 027 trial / 
1. Investigational product use permanently discontinued in response 
to an AE (where the AE was considered related to investigational 
product) or safety-related concern while taking part in the IPM 027 
trial / 
 
B / 
2. Available for all visits and consent to follow all procedures 
scheduled for the trial / 
2. Currently pregnant, intending to become pregnant, or currently 
breast-feeding / 
 
C  
3. Using an effective method of contraception at the Enrolment Visit, 
and intending to use an effective contraceptive method for the duration 
of trial participation, unless post-menopausal with no history of 
menses for one year prior to screening / 
3. Known drug abuse or alcohol dependence in the 12 months prior 
to screening / 
 
 
4.  HIV-negative as determined by the HIV algorithm applied 
at Screening/Pre-Enrolment / 
4. Participated in another research trial (other than IPM 027) using 
drugs, medical devices, microbicides or oral pre-exposure 
prophylaxis agents within 30 days prior to screening / 
 
 
5. Willing to refrain from participation in another research trial using 
drugs, vaccines, medical devices and microbicides for the duration of 
the IPM 032 trial / 
5. Any new illness or condition(s), chronic condition(s) or abnormal 
laboratory finding(s) that, in the opinion of the investigator, might put 
the participant at risk, or interfere with the trial objectives or the 
participant’s adherence to trial requirements 
 
 
6. Willing to provide adequate locator information for trial 
retention purposes and be reachable per local standard 
procedures (e.g. by home visit or telephone; or via family 
or close neighbour contacts); confidentiality to be 
maintained 
 
 
 
 
 
Programmers Notes:  
- Populate IPM027 Exit Date with whichever is later, LPUV or Exit Visit. 
- Please note that the incl/excl criteria is that of the the participants who were previously exposed to the DVR; see p. 13/14 of the protocol for the incl/excl criteria of the DVR 
naïve cohort 
 
 
 
 
AE = Adverse event; EXCL = Exclusion criteria; INCL = Inclusion criteria; LPUV = Last product use visit 
Visit Schedule A = Participants attended trial month visit 1, 4, 7, 10, 13 and 16/Exit 
Visit Schedule B = Participants attended trial month visit 1, 2, 5, 8, 11, 14 and 17/Exit 
Visit Schedule C = Participants attended trial month visit 1, 2, 3, 6, 9, 12 and 15/Exit 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
Listing 16.2.1.1 
Enrollment 
Safety Population 
 
 
Page 6 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
IPM027 LPUV and IPM032  
IPM027  
IPM027  
Comments 
  Participant ID 
Schedule 
Screening / Enrollment 
Exit Date 
Participant 
 
 
 
Visits Combined 
 
ID 
 
 
 
 
 
 
 
Centre XX 
A / 
 
 
 
 
   XXXXXXXX 
B / 
Yes /  
ddMMMyyyy 
XXXXXXX / 
 
 
C  
No 
 
None 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes:  
- Populate IPM027 Exit Date with whichever is later, LPUV or Exit Visit. 
- Please note that the incl/excl criteria is that of the the participants who were previously exposed to the DVR; see p. 13/14 of the protocol for the incl/excl criteria of the DVR 
naïve cohort 
 
 
 
 
 
 
AE = Adverse event; EXCL = Exclusion criteria; INCL = Inclusion criteria; LPUV = Last product use visit 
Visit Schedule A = Participants attended trial month visit 1, 4, 7, 10, 13 and 16/Exit 
Visit Schedule B = Participants attended trial month visit 1, 2, 5, 8, 11, 14 and 17/Exit 
Visit Schedule C = Participants attended trial month visit 1, 2, 3, 6, 9, 12 and 15/Exit 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
Listing 16.2.1.2 
Screen Failures 
All Participants 
 
 
Page 7 of 154 
 
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Centre 
Screen Failure 
Date of Signed 
Consent Version  Reason(s) for  
Incl Criteria Not Met 
  Screening ID 
Date 
Consent 
No. and Date 
Ineligibility 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
ddMMMyyyy 
XX-ddMMMyyyy 
INCL not met / 
1. Previously enrolled in the IPM 027 trial / 
 
 
 
 
EXCL met / 
2. Available for all visits and consent to follow all procedures 
scheduled for the trial / 
 
 
 
 
Other: Xxxxxxxx 
3. Using an effective method of contraception at the Enrolment Visit, and 
intending to use an effective contraceptive method for the duration of trial 
participation, unless post-menopausal with no history of menses for one year 
prior to screening / 
 
 
 
 
 
4.  HIV-negative as determined by the HIV algorithm applied 
at Screening/Pre-Enrolment / 
 
 
 
 
 
5. Willing to refrain from participation in another research trial using drugs, 
vaccines, medical devices and microbicides for the duration of the IPM 032 trial / 
 
 
 
 
 
6. Willing to provide adequate locator information for trial retention purposes and 
be reachable per local standard procedures (e.g. by home visit or telephone; or 
via family or close neighbour contacts); confidentiality to be maintained 
 
 
 
 
 
 
Programmers Notes: 
-  Please capture multiple responses, separated with a ‘;’ 
- Please note that the incl/excl criteria is that of the the participants who were previously exposed to the DVR; see p. 13/14 of the protocol for the incl/excl criteria of the DVR 
naïve cohort 
 
 
 
 
 
 
AE = Adverse; Excl = Exclusion; Incl = Inclusion 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
Listing 16.2.1.2 
Screen Failures 
All Participants 
 
 
Page 8 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Screen Failure 
Excl Criteria Met 
IPM 027 
Comment 
  Screening ID 
Date 
 
PID 
 
 
 
 
 
 
Centre XX 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
1. Investigational product use permanently discontinued in 
response to an AE (where the AE was considered related to 
investigational product) or safety-related concern while taking part 
in the IPM 027 trial / 
XXXXXXXXX 
 
 
 
2. Currently pregnant, intending to become pregnant, or currently 
breast-feeding / 
 
 
 
 
3. Known drug abuse or alcohol dependence in the 12 months prior 
to screening / 
 
 
 
 
4. Participated in another research trial (other than IPM 027) using 
drugs, medical devices, microbicides or oral pre-exposure 
prophylaxis agents within 30 days prior to screening / 
 
 
 
 
5. Any new illness or condition(s), chronic condition(s) or abnormal 
laboratory finding(s) that, in the opinion of the investigator, might 
put the participant at risk, or interfere with the trial objectives or the 
participant’s adherence to trial requirements 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
-  Please capture multiple responses, separated with a ‘;’ 
- Please note that the incl/excl criteria is that of the the participants who were previously exposed to the DVR; see p. 13/14 of the protocol for the incl/excl criteria of the DVR 
naïve cohort 
 
 
 
 
 
AE = Adverse; Excl = Exclusion; Incl = Inclusion 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


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IPM 032 
 
Listing 16.2.1.3 
Participant Disposition: Participant Visits 
Safety Population 
 
 
Page 9 of 154 
 
Version 1.0 
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Centre 
Visit Date 
Visit 
Enrollment  
Type of Visit 
Reason(s) for Unscheduled Visit 
Completion 
Completion 
  Participant ID 
 
 
Date 
 
 
Date 
Status 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
ddMMMyyyy 
Scheduled / 
Intends to withdraw / 
ddMMMyyyy 
Completed the 
trial / 
 
 
Enrollment / 
 
Unscheduled / 
Blood draw or additional testing / 
 
Discontinued 
early 
 
 
Trial Month XX / 
 
LPUV / 
HIV testing / 
 
 
 
 
Trial Month XX  
 
Exit visit 
Suspected/confirmed pregnancy / 
 
 
 
 
(Unscheduled X) / 
 
 
Report social harm / 
 
 
 
 
Exit visit 
 
 
Return/collect study product / 
 
 
 
 
 
 
 
Treatment/follow-up of AE or medical condition / 
 
 
 
 
 
 
 
Other: XXXXXX 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
AE = Adverse event; LPUV = Last product use visit 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


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IPM 032 
 
Listing 16.2.1.3 
Participant Disposition: Participant Visits 
Safety Population 
 
 
Page 10 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit Date 
Visit 
Enrollment  
Type of Visit 
Reasons for Early Completion 
Comments 
  Participant ID 
 
 
Date 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
ddMMMyyyy 
Scheduled / 
Participant withdrew consent: Relocation / 
 
 
 
Enrollment / 
 
Unscheduled / 
Participant withdrew consent: Employment/work / 
 
 
 
Trial Month XX / 
 
LPUV / 
Participant withdrew consent: Family/partner pressure / 
 
 
 
Trial Month XX  
 
Exit visit 
Participant withdrew consent: Other / 
 
 
 
(Unscheduled X) / 
 
 
Non-compliance: Xxxxxxxxx / 
 
 
 
Exit visit 
 
 
Lost to follow-up / 
 
 
 
 
 
 
Adverse event/intercurrent illness: Xxxxxxx / 
 
 
 
 
 
 
Inappropriate enrollment / 
 
 
 
 
 
 
HIV seroconversion / 
 
 
 
 
 
 
Pregnancy / 
 
 
 
 
 
 
Sponsor terminated the trial / 
 
 
 
 
 
 
Death / 
 
 
 
 
 
 
Other 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
AE = Adverse event; LPUV = Last product use visit 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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IPM 032 
 
Listing 16.2.1.4 
Missed Visits 
Safety Population 
 
 
Page 11 of 154 
 
Version 1.0 
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Centre 
Visit 
Reason for Missed Visits 
Comments 
  Participant ID 
 
 
 
 
 
 
 
Centre XX 
 
 
 
   XXXXXXXX 
Screening / 
Unable to contact participant / 
 
 
Enrollment / 
Unable to attend schedule appointment(s) within  
 
 
Trial Month XX / 
a permitted window: Participant found new employment / 
 
 
Trial Month XX (Unscheduled X) / 
Unable to attend schedule appointment(s) within 
 
 
Exit visit 
a permitted window: Participant relocated / 
 
 
 
Unable to attend schedule appointment(s) within 
 
 
 
a permitted window: Other: Xxxxxxxxxxxxxxxxxxx / 
 
 
 
Participant refused visit / 
 
 
 
Participant admitted to a health care facility / 
 
 
 
Participant withdrew from study / 
 
 
 
Death / 
 
 
 
Other: Xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


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IPM 032 
 
 
 
 Listing 16.2.2.1 
Protocol Deviations 
Safety Population 
Deviation type: Minor 
 
Page 12 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Date of  
Deviation Category  
Description of Deviation 
Description of Deviation  
Action Taken to Resolve) 
  Participant ID 
Deviation 
 
 
(Verbatim) 
Deviation (Verbatim) 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Inappropriate enrollment: INCL / 
 
 
 
 
 
Inappropriate enrollment: EXCL / 
 
 
 
 
 
Missed visit / 
 
 
 
 
 
Visit completed outside 
 
 
 
 
 
permissible period: 
 
 
 
 
 
Trial month XX.X / 
 
 
 
 
 
Other (code) / 
 
 
 
 
 
Other: Xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- Please populate Description of Deviation with the appropriate (IPM 027/DPR-naïve) INCL/EXCL criteria or Other (code) text  
- Please repeat for Deviation type: Major / None  
 
 
 
 
 
 
 
 
 
 
 
 
EXCL = Exclusion criteria; INCL = Inclusion criteria  
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 
 


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IPM 032 
 
 
 
 Listing 16.2.3.1 
Analysis Populations 
Safety Population 
 
 
Page 13 of 154 
 
Version 1.0 
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Centre 
Participant ID 
Safety 
m-ITT 
Virology 
PP 
 
 
 
 
 
 
Centre XX 
XXXXXXXX 
Yes  
Yes / 
Yes / 
Yes / 
 
 
 
No 
No 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
m-ITT = Modified intent-to-treat population; PP = Per-protocol population 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
 Listing 16.2.4.1 
Demographics at Screening 
Safety Population 
 
 
Page 14 of 154 
 
Version 1.0 
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Education 
 
Centre 
Visit Date 
Date of 
Race 
Age 
Height 
Weight 
BMI 
Primary  
Secondary 
Tertiary Level: 
Marital 
  Participant ID 
 
Birth 
 
(Years) 
(cm) 
(kg) 
(kg/m2) 
School 
School 
No. of Years 
Status 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
ddMMMyyyy 
Coloured / 
XX 
XXXX 
XXX 
XX.X 
Yes /  
Yes /  
Yes: XX / 
Married / 
 
 
 
Asian / 
 
 
 
 
No 
No 
No 
Separated / 
 
 
 
Black / 
 
 
 
 
 
 
 
Divorced / 
 
 
 
White / 
 
 
 
 
 
 
 
Widowed / 
 
 
 
Indian / 
 
 
 
 
 
 
 
Single 
 
 
 
Other: 
Xxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple STIs, separated with a ‘;’ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Age = INT((Enrollment Date – Date of Birth)/365.25); Body Mass Index (BMI)  = (Weight in kg)/(Height in m)2 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 
 


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IPM 032 
 
 
 
 Listing 16.2.4.1 
Demographics at Screening 
Safety Population 
 
 
Page 15 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Main Sex 
Length of 
Current Co-Residential 
Co-Residential Status with Main 
Vaginal Sex Once  
Usual No.  
No. of Male  
Has  
  Participant ID 
Partner 
Partnership 
Status with Main 
Partner (Past Year) 
a Week or More 
of Vaginal 
Sex Partners 
Children 
 
 
(Years) 
Partner 
 
in Past Month 
Sex Acts 
at Baseline 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
   XXXXXXXX 
Yes 
XX / 
Yes / 
Lived together all the time / 
Yes /  
XX 
XX 
Yes / 
 
No 
< 1  
No 
Lived together some of the time / 
No 
 
 
No 
 
 
 
 
Lived together none of the time 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple STIs, separated with a ‘;’ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Age = INT((Enrollment Date – Date of Birth)/365.25); Body Mass Index (BMI)  = (Weight in kg)/ (Height in m)2 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


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IPM 032 
 
 
 
 Listing 16.2.4.1 
Demographics at Screening 
Safety Population 
 
 
Page 16 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Genital Symptom  
Partner Knowledge of Ring Use / 
Directly From 
IPM 027 
Comments 
  Participant ID 
STIs at Screening 
Study Participation 
IPM 027? 
Treatment 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
Trichomonas / 
Knows about the study and ring / 
Yes / 
Dapivirine / 
 
 
Gonorrhoea / 
Only knows that I am in a study / 
No 
Placebo 
 
 
Chlamydia / 
Only knows that I am wearing a ring / 
 
 
 
 
Syphilis 
Doesn’t know about the study or the ring / 
 
 
 
 
 
Don’t know 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple STIs, separated with a ‘;’ 
 
 
 
 
 
 
 
 
 
 
 
 
 
Age = INT((Enrollment Date – Date of Birth)/365.25); Body Mass Index (BMI)  = (Weight in kg)/ (Height in m)2 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


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IPM 032 
 
 
 
 Listing 16.2.4.2 
Demographics at Screening 
Virology Population 
 
 
Page 17 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Seroconverted 
Centre - Participant 
Age 
Date of 
Height 
Weight 
BMI 
Country 
Race 
Marital 
 
ID 
(Years) 
Seroconversion 
(cm) 
(kg) 
(kg/m2) 
 
 
Status 
 
 
 
 
 
 
 
 
 
 
Yes (On IP)/ 
XX- XXXXXXXX 
XX 
ddMMMyyyy 
XXXX 
XXX 
XX.X 
South Africa / 
Coloured / 
Married / 
Yes (Prior to IP) / 
  
 
 
 
 
 
Zimbabwe / 
Asian / 
Separated / 
Yes (After IP) / 
 
 
 
 
 
 
Uganda 
Black / 
Divorced / 
No 
 
  
 
 
 
 
 
White / 
Widowed / 
 
 
 
 
 
 
 
 
Indian / 
Single 
 
 
 
 
 
 
 
 
Other: Xxxxxx 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- Please capture multiple STIs, separated with a ‘;’ 
- Please sort listing by seroconversion status and PID 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Age = INT((Enrollment Date – Date of Birth)/365.25); Body Mass Index (BMI)  = (Weight in kg)/ (Height in m)2 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


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IPM 032 
 
 
 
 Listing 16.2.4.2 
Demographics at Screening 
Virology Population 
 
 
Page 18 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Seroconverteda 
Centre - Participant 
Has Children 
Genital Symptom STIs 
No. of Male Sex 
HIV-1 Subtype 
Directly From 
IPM 027 
 
ID 
 
at Baseline 
Partners at Screening 
 
IPM 027? 
Treatment 
 
 
 
 
 
 
 
 
No / 
XX- XXXXXXXX 
Yes / 
Trichomonas / 
XX 
C / 
 
 
Yes (on) / 
  
No 
Gonorrhoea / 
 
A1 
Yes / 
Dapivirine / 
Yes (prior) / 
 
 
Chlamydia / 
 
 
No 
Placebo 
Yes (after) 
 
 
Syphilis 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- Please capture multiple STIs, separated with a ‘;’ 
- Please sort listing by seroconversion status and PID 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Age = INT((Enrollment Date – Date of Birth)/365.25); Body Mass Index (BMI)  = (Weight in kg)/ (Height in m)2 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


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IPM 032 
 
 
 
 Listing 16.2.4.3 
Medical History at Screening 
Safety Population 
 
 
Page 19 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Condition / 
Severity  
Onset 
Ongoing at 
Comments 
  Participant ID 
Diagnosis 
Grade 
Date 
Enrollment 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
 
X / 
ddMMMyyyy 
Yes / No 
 
 
 
Not gradable 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 
 
 
 
 
 
 
 
 
 


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IPM 032 
 
 
 
 Listing 16.2.4.4 
Contraceptive/ Menstrual/ Obstetric History at Screening 
Safety Population 
 
 
Page 20 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
Contraceptive Method 
 
Menstruation History 
Centre 
Visit 
Current Method 
CM Name 
 
Menstrual Bleeding 
Duration of  
Duration of  
  Participant ID 
Date 
 
 
 
(Past 6 Months) 
Menstrual  
Menstrual Bleeding 
 
 
 
 
 
 
Cycle (Days) 
 (Days) 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Oral contraceptive regimen / 
 
 
Regular cycle / 
XX  
XX  
 
 
Transdermal contraceptive 
 
 
Irregular cycle (associated with 
 
 
 
 
patch / 
 
 
contraceptive use) / 
 
 
 
 
Long acting injectable 
 
 
Amenorrhoeic 
 
 
 
 
progestins / 
 
 
 
 
 
 
 
Condoms / 
 
 
 
 
 
 
 
Subcutaneous implant / 
 
 
 
 
 
 
 
IUD / 
 
 
 
 
 
 
 
Surgical sterilization / 
 
 
 
 
 
 
 
Other: Xxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please list all Contraceptive Methods and applicable CM Names separated with a  ‘;’ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CM = Concomitant medication; IUD = Intrauterine device 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


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IPM 032 
 
 
 
 Listing 16.2.4.4 
Contraceptive/ Menstrual/ Obstetric History at Screening 
Safety Population 
 
 
Page 21 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
Menstruation History 
 
Obstetric History 
 
Centre 
Visit 
Menstrual  
Dysmenorrhea 
 
Gravidity 
Parity 
No. of Vaginal 
No. of C- 
Comments 
  Participant ID 
Date 
Flow 
History 
 
 
 
Deliveries 
Sections 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Light / 
Yes / No 
 
XX 
XX 
XX 
XX 
 
 
 
Moderate / 
 
 
 
 
 
 
 
 
 
Heavy 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please list all Contraceptive Methods and applicable CM Names separated with a ‘;’ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CM = Concomitant medication; IUD = Intrauterine device 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 
 
 
 
 
 


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IPM 032 
 
 
 
 Listing 16.2.4.5 
Gynaecological History at Screening 
Safety Population 
 
 
Page 22 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
 
 
 
Centre 
Subcategory of Medical History 
System Organ Class /  
Severity  
Onset 
Ongoing at  
  Participant ID 
 
Condition or Diagnosis 
Grade 
 
enrollment 
 
 
 
 
 
 
Centre XX 
 
 
 
ddMMMyyyy 
Y / 
   XXXXXXX 
 
 
 
 
N 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Gynaecological conditions were coded using Version 19.0 of the Medical Dictionary for Regulatory Activities (MedDRA) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
 Listing 16.2.4.6 
Prior Medication 
Safety Population 
 
 
Page 23 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Medication Name 
Indication 
Dose  
Route 
Frequency 
Start Date 
End Date 
  Participant ID 
 
 
(Units) 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
 
Contraceptive / 
XXX (unit) 
PO / 
pm / 
ddMMMyyyy 
ddMMMyyyy / 
 
 
Xxxxxxxxxxxx 
 
IU / 
bid / 
 
Ongoing 
 
 
 
 
VAG / 
phs / 
 
 
 
 
 
 
IM / 
once / 
 
 
 
 
 
 
TOP / 
tid / 
 
 
 
 
 
 
REC / 
qd / 
 
 
 
 
 
 
IV / 
qid / 
 
 
 
 
 
 
UHL / 
Other: Xxxxxx 
 
 
 
 
 
 
SC / 
 
 
 
 
 
 
 
Other:  
 
 
 
 
 
 
 
Xxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
Programmers note: Please add abbreciations of Frequency to the footnote (where applicable) 
 
 
 
 
 
 
 
 
Prior medication is defined as any medication that started and ended before the first insertion of the investigational product (IP) 
Medications were coded using the World Health Organization Drug Dictionary Enhanced (WHO DDE; version June 2017) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
 Listing 16.2.4.7 
Concomitant Medication 
Safety Population 
 
 
Page 24 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Medication Name 
Taken for AE: 
Indication 
Dose  
Route 
Frequency 
Start Date 
End Date 
  Participant ID 
 
Description 
 
(Units) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
   XXXXXXXX 
 
Yes: Xxxxxxxxxxxx / 
Contraceptive / 
XXX (unit) 
PO / 
pm / 
ddMMMyyyy 
ddMMMyyyy / 
 
 
No 
Xxxxxxxxxxxx 
 
IU / 
bid / 
 
Ongoing 
 
 
 
 
 
VAG / 
phs / 
 
 
 
 
 
 
 
IM / 
once / 
 
 
 
 
 
 
 
TOP / 
tid / 
 
 
 
 
 
 
 
REC / 
qd / 
 
 
 
 
 
 
 
IV / 
qid / 
 
 
 
 
 
 
 
UHL / 
Other:  
 
 
 
 
 
 
 
SC / 
Xxxxxx 
 
 
 
 
 
 
 
Other:  
 
 
 
 
 
 
 
 
Xxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers note: Please add abbreciations of Frequency to the footnote (where applicable) 
 
 
 
 
 
 
 
 
 
AE = Adverse event 
Concomitant medication is defined as any medication taken in conjunction with the investigational product (IP). This includes any medication that started after the first insertion of the IP, 
or started before the first insertion of the IP but ended on/after the first insertion of the IP 
Medications were coded using the World Health Organization Drug Dictionary Enhanced (WHO DDE; version June 2017) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
 Listing 16.2.5.1 
Adherence to Investigational Product 
Safety Population 
 
 
Page 25 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Used in 
Enrollment  
Parameter 
Residual  
Batch 
IPM 027 
Comments 
  Participant ID 
Month  
Date 
 
Dapivirine 
No. 
Treatment 
 
 
No. 
 
 
(mg) 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
XX 
ddMMMyyyy 
 
 
 
Dapivirine / 
 
 
 
 
 
 
 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


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IPM 032 
 
 
 
 Listing 16.2.5.2 
Self-Reported Acceptability and Adherence to Investigational Product 
Safety Population 
 
 
Page 26 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
IPM 027 
Date  
Date 
Duration of  
Scheduled Duration 
Adherence Rate 
Adherence Rate Category 
  Participant ID 
Date 
Treatment 
Inserted 
Removed 
Treatment 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Dapivirine / 
ddMMMyyyy  
ddMMMyyyy  XX  
XX  
XXX  
< 80% 
 
 
Placebo 
 
 
 
 
 
≥ 80 to < 90% / 
 
 
 
 
 
 
 
 
≥ 90%  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adherence rate = 100 x (Duration of Treatment / Scheduled Duration) 
Missing or partial dates for when the ring was inserted or removed are treated as missing data during the calculation of the adherence rate 
If a participant did not remember/know the date when a ring was expelled or removed, the number of days that the ring was out is counted as one day and applies to the ring that was 
dispensed during that time 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.2 
Self-Reported Acceptability and Adherence to Investigational Product 
Safety Population 
 
 
Page 27 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Do You Think It Is Possible To Use Ring As Requested 
Do You Think Women In Your Community Would Like To Use This Ring If It 
  Participant ID 
Date 
(i.e. Without Removing It)? 
Were Available? 
 
 
 
 
Centre XX 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Yes / 
Yes / 
 
 
No: Xxxxxxxxxxxxxxx / 
No: Xxxxxxxxxxxxxxxxxxxx / 
 
 
Don’t know / 
Chose not to answer  
 
 
Chose not to answer  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adherence rate = 100 x (Duration of Treatment / Scheduled Duration) 
Missing or partial dates for when the ring was inserted or removed are treated as missing data during the calculation of the adherence rate 
If a participant did not remember/know the date when a ring was expelled or removed, the number of days that the ring was out is counted as one day and applies to the ring that was 
dispensed during that time 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.3 
Returned Ring Log 
Safety Population 
 
 
Page 28 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Participant 
Month of Ring  
Replacement  
Shipped for 
Shipped  
Shared Results with 
Results Shared 
 
ID 
Use 
Ring 
Analysis 
Date 
Participant 
Date 
 
 
 
 
 
 
 
 
XX 
XXXXXXXXX 
XX 
Yes / 
Yes / 
ddMMMyyyy 
Yes /  
ddMMMyyyy 
 
 
 
No 
No 
 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.4 
Ring Insertion/ Removal 
Safety Population 
 
 
Page 29 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
Dispensed 
 
Insertion 
Centre 
Month To Be  Batch  
Replacement 
Visit  
Dispensed 
 
Inserted 
Insertion 
Re- 
  Participant ID 
Used In 
No. 
Ring 
Dispensed 
Date 
 
Ring 
Date 
Educated? 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
   XXXXXXXX 
XX 
XXXXXX 
Yes / No 
Screening / 
ddMMMyyyy 
 
Yes /  
ddMMMyyyy 
Yes / 
 
 
 
 
Enrollment / 
 
 
No:  
 
No 
 
 
 
 
Trial Month XX / 
 
 
Xxxxxxxxxxxx 
 
 
 
 
 
 
Trial Month XX  
 
 
 
 
 
 
 
 
 
(Unscheduled X) / 
 
 
 
 
 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Duration of Ring Use = (Removal Date – Inserted Date)+1 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.4 
Ring Insertion/ Removal 
Safety Population 
 
 
Page 30 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
Removal 
Centre 
Removal 
Duration of 
Required  
Re- 
Ring Returned  
Reason Not Returned 
  Participant ID 
Date 
Ring Use 
Assistance  
Educated? 
to Research  
to Research Centre 
 
 
(Days) 
with Removal 
 
Centre 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
XX 
Yes / 
Yes / 
Yes /  
Lost ring / 
 
 
 
No 
No 
No 
Flushed down toilet / 
 
 
 
 
 
 
Forgot ring / 
 
 
 
 
 
 
Discarded ring / 
 
 
 
 
 
 
Other: Xxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Duration of Ring Use = (Removal Date – Inserted Date)+1 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.4 
Ring Insertion/ Removal 
Safety Population 
 
 
Page 31 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
Return 
 
Centre 
Visit 
Return 
Package  
Appearance of  
Color of Returned 
Other Comments 
Comments 
  Participant ID 
Returned 
Date 
Opened 
Returned Ring 
Ring 
on Appearance  
 
 
 
 
 
 
 
of Ring 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
Screening / 
ddMMMyyyy 
Yes / 
Appears used:  
White to off-white 
 
 
 
Enrollment / 
 
No 
Xxxxxxxx / 
cream-colored / 
 
 
 
Trial Month XX / 
 
 
Appears not used:  
Slight yellow to  
 
 
 
Trial Month XX  
 
 
Xxxxx / 
yellow / 
 
 
 
(Unscheduled X) / 
 
 
Not sure:  
Tan / 
 
 
 
Exit visit 
 
 
Xxxxxxxxx 
Brown / 
 
 
 
 
 
 
 
Other color:  
 
 
 
 
 
 
 
Xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
Duration = (Removal Date – Inserted Date)+1 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.5 
Accidental Expulsion/ Removal Log 
Safety Population 
 
 
Page 32 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Date of Accidental 
Time of Expulsion / 
Expulsion / 
Date of Re- 
Time of Re- 
Why Was Ring Removed /  
Category for 
  Participant ID 
Expulsion / Removal 
Removal 
Removal 
Insertion 
Insertion 
Why Did Ring Come Out? 
Removal 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
hh:mm 
Expulsion / 
ddMMMyyyy / 
hh:mm  
 
Removed by participant / 
 
 
 
Removal 
Not re-inserted 
 
 
Colposcopy / 
 
 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.6 
Participant Questionnaire – Part A (Month 1, 2 and 3) 
Safety Population 
 
 
Page 33 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Question 
Question 
No. 
 
 
 
1 
As per investigator decision, are you coming to the research centre next month, or in three months for your next visit? 
2 
Will you take your extra rings with you today or will you come back to the research centre each month to pick up your new ring? 
3 
What are your reasons for leaving the rings at the research centre today? 
4 
Does your main partner know you are in the study and wearing a vaginal ring? 
5 
The research centre staff showed you how to insert and remove your ring. You were also given an instruction sheet that explains this. Was the sheet helpful, 
 
or does it need to be changed? 
 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.6 
Participant Questionnaire – Part A (Month 1, 2 and 3) 
Safety Population 
 
 
Page 34 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q1 
Q2 
Q3 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Next month / 
Take them all / 
Do not want anyone to see the rings / 
 
 
Enrollment / 
In 3 months 
Collect monthly from centre / 
Do not have a private place to keep unused 
 
 
Trial Month XX / 
 
Chose not to answer 
rings at home / 
 
 
Trial Month XX  
 
 
Do not have a private place to keep used 
 
 
(Unscheduled X) / 
 
 
rings at home / 
 
 
Exit visit 
 
 
Do not have an appropriate storage place to 
 
 
 
 
 
keep the rings (used or unused) at home / 
 
 
 
 
 
Do not have a private place to insert the 
 
 
 
 
 
rings at home / 
 
 
 
 
 
Worried I might lose the ring(s) / 
 
 
 
 
 
Feel I might forget to insert the new ring if I 
 
 
 
 
 
don’t come each month / 
 
 
 
 
 
Like coming to the research centre for HIV tests  
 
 
 
 
 
each month / 
 
 
 
 
 
Like coming to the research centre monthly for  
 
 
 
 
 
social reasons / 
 
 
 
 
 
Other: Xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx / 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.6 
Participant Questionnaire – Part A (Month 1, 2 and 3) 
Safety Population 
 
 
Page 35 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q4 
Q5 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Knows about the study and the ring / 
Good as is / 
 
 
Enrollment / 
Only knows that I am in a study / 
Hard to understand / 
 
 
Trial Month XX / 
Only knows that I am wearing a ring / 
Needs more information: Xxxxxxxxxxxxxxxxxxxx / 
 
 
Trial Month XX  
Doesn’t know about the study or the ring / 
Needs to be changed: Xxxxxxxxxxxxxxxxxxxxx / 
 
 
(Unscheduled X) / 
Don’t know / 
Did not read the instruction sheet / 
 
 
Exit visit 
Chose not to answer 
Can’t remember the sheet / 
 
 
 
 
Chose not to answer 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.7 
Participant Questionnaire – Part B (Month 2 and 3 Only) 
Safety Population 
 
 
Page 36 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Question 
Question 
No. 
 
 
 
1 
Has your ring been removed/expelled since your last scheduled visit? 
2 
What was the reason the ring was removed/expelled since the last scheduled visit? 
3 
When the ring was removed/expelled did you clean the ring before reinsertion? 
4 
What did you use to clean the ring when it was removed or expelled? 
5 
For those participants who removed their ring: Thinking back since your last scheduled visit, was it easy or difficult to remove your ring? 
6 
Thinking back since your last scheduled visit, when you inserted a new ring, was it easy or difficult? 
7 
At each regularly scheduled visit, you gave a sample of blood and vaginal fluids. Please tell me what your preferences are. 
8 
Below is a list of things that some women may like about participating in this study (DREAM). Please order these, where 1 means you liked it the most 
 
and 5 means you liked it the least. 
9 
I’m going to read a list of things that some women have experienced during other study/studies. Please tell me if you have experienced any of these things in  
 
this study (DREAM). 
9.a 
Length of time spent at the research centre for the study visits was too long. If Yes, specify how long. 
9.b 
Transport to the research centre for scheduled visits was a problem. If Yes, specify. 
9.c 
I was treated well when coming to the research centre for regular visits. 
9.d 
If partner knows about participation: My partner id happy about my participation in the study. 
9.e 
My neighbors, family, or friends know about my participation in this study. If yes, specify if neighbor/friends/family. 
9.f 
If neighbor, friends, or family knows about participation (see above): My neighbors, family, or friends (as above) are happy about my participation in this study. 
9.g 
Other 
10 
If you were not in a study, would you prefer to come to the health care clinic/provider for new rings each month, or every three months? 
11 
If you were not in a study, would you prefer to come to the health care clinic/provider for an HIV test each month, or every three months? 
 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.7 
Participant Questionnaire – Part B (Month 2 and 3 Only) 
Safety Population 
 
 
Page 37 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q1 
Q2 
Q3 
Q4 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Removed: Uncomfortable/painful / 
Yes / 
Water only / 
 
 
Enrollment / 
No / 
Removed: Cleaning / 
No / 
Body wash soap only / 
 
 
Trial Month XX / 
Chose not to answer 
Removed: Menses / 
Chose not to  
Water and body wash soap / 
 
 
Trial Month XX  
 
Removed: Real/perceived side 
answer 
Disinfectant: Xxxxxxxxxx / 
 
 
(Unscheduled X) / 
 
effects: Xxxxxxxxxxxx / 
 
Herbal product: Xxxxxxxxxx / 
 
 
Exit visit 
 
Removed: Partner request / 
 
Traditional medicine: Xxxxxxx / 
 
 
 
 
Removed: Sex / 
 
Bubble bath: Xxxxxxxxxx / 
 
 
 
 
Removed: Keep from partner / 
 
Bath salts: Xxxxxxxxx / 
 
 
 
 
Accident: Xxxxxxxxxxxxxxx / 
 
Dishwashing liquid: Xxxxxxxxx / 
 
 
 
 
Other: Xxxxxxxxxxxxxx / 
 
Other: Xxxxxxxxxxxxxx / 
 
 
 
 
Chose not to answer 
 
Chose not to answer 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.7 
Participant Questionnaire – Part B (Month 2 and 3 Only) 
Safety Population 
 
 
Page 38 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q5 
Q6 
Q7a: Blood Samples 
Q7b: Vaginal Fluid Samples 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Easy / 
Easy / 
Taken at every visit / 
Taken at every visit / 
 
 
Enrollment / 
Difficult / 
Difficult / 
Taken less often / 
Taken less often / 
 
 
Trial Month XX / 
Bit of both / 
Bit of both / 
N/A / 
N/A / 
 
 
Trial Month XX  
Neither / 
Neither / 
Chose not to answer 
Chose not to answer 
 
 
(Unscheduled X) / 
N/A / 
N/A / 
 
 
 
 
Exit visit 
Chose not to answer 
Chose not to answer 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.7 
Participant Questionnaire – Part B (Month 2 and 3 Only) 
Safety Population 
 
 
Page 39 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q8: Rank  
Q9 
Q9a 
Q9b 
Q9c 
Q9d 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Regular HIV testing: X / 
Answered / 
Yes: Xxxx / 
Yes: Xxxx / 
Yes / 
Yes / 
 
 
Enrollment / 
Other health benefits: X / 
Chose not to  
No  
No  
No  
No / 
 
 
Trial Month XX / 
Reimbursement money: X / 
answer 
 
 
 
N/A 
 
 
Trial Month XX  
Meeting other study participants: X / 
 
 
 
 
 
 
 
(Unscheduled X) / 
Helping others in future: X / 
 
 
 
 
 
 
 
Exit visit 
Chose not to answer 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.7 
Participant Questionnaire – Part B (Month 2 and 3 Only) 
Safety Population 
 
 
Page 40 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q9e 
Q9f 
Q9g  
Q9g 
Q10 
Q11 
  Participant ID 
Date 
 
 
 
Experience 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes: Friends / 
Yes / 
 
Yes / 
Each month / 
Each month / 
 
 
Enrollment / 
Yes: Family / 
No / 
 
No / 
Every 3 months / 
Every 3 months / 
 
 
Trial Month XX / 
Yes: Neighbor / 
N/A 
 
N/A 
Don’t mind / 
Don’t mind / 
 
 
Trial Month XX  
No / 
 
 
 
Depends: Xxxxxxxxxx / 
Depends: Xxxxxxxxxx / 
 
 
(Unscheduled X) / 
 
 
 
 
Chose not to answer 
Chose not to answer 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.8 
Participant Questionnaire – Part C (Month 1, 2, and 3) 
Safety Population 
 
 
Page 41 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Question 
Question 
No. 
 
 
 
1 
Do you currently have a main sex partner?  
1a  
How long has he been your partner? 
2 
Do you and your main partner currently live together? 
3 
Have you had any other partners in the past 3 months? 
3a 
If yes, indicate number. 
4 
We need to know how often you usually have sex. Think about the past four weeks, which is about one month. Over the past four weeks, how many rounds of  
 
vaginal sex did you have? 
5 
In the past month, how frequently did you use a male condom during vaginal sex? 
6 
In the past month, how frequently did you use a female condom during vaginal sex? 
7 
During the last round of vaginal sex you had, did you use a condom? 
8 
In the past year, have you had anal sex?  
8a 
If yes, did you use a condom? 
9 
How worried are you that you might get infected with HIV in the next year? 
10 
In the past 3 months, have you had any menstrual bleeding or any menstrual spotting? 
11 
In the past 3 months, what have you used to control or manage the menstrual blood or spotting? Mark all that apply, using numbers for only those that apply -  
 
with 1 for the item used most, 2 for next most frequent, and so on until least frequent. 
12 
Since your last scheduled visit, have you inserted your fingers into your vagina for any reason? 
13 
What was the reason for inserting your fingers into your vagina? 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.8 
Participant Questionnaire – Part C (Month 1, 2, and 3) 
Safety Population 
 
 
Page 42 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q1 
Q1a 
Q2 
Q3 
Q3a 
Q4 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
XXX months / 
Yes / 
Yes / 
XXX / 
XXX / 
 
 
Enrollment / 
No / 
XXX years / 
No / 
No / 
Chose  
Chose not  
 
 
Trial Month XX / 
Chose not  
Chose not  
Chose not  
Chose  
not to answer 
to answer 
 
 
Trial Month XX  
to answer 
to answer 
to answer 
not to answer 
 
 
 
 
(Unscheduled X) / 
 
 
 
 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
 
Rank: 1 = Used most frequent; 2 = Used second most frequent; 3 = Frequently used; 4 = Used a little; 5 = Least used 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.8 
Participant Questionnaire – Part C (Month 1, 2, and 3) 
Safety Population 
 
 
Page 43 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q5 
Q6 
Q7 
Q8 
Q8a 
Q9 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Always / 
Always / 
Yes male condom / 
Yes / 
Yes / 
Very  / 
 
 
Enrollment / 
Sometimes / 
Sometimes / 
Yes female condom 
No / 
No / 
A little / 
 
 
Trial Month XX / 
Often / 
Often / 
No / 
Chose not  
Sometimes / 
Not at all / 
 
 
Trial Month XX  
Never / 
Never / 
Chose not to answer 
to answer 
Chose not to answer 
Chose not 
 
 
(Unscheduled X) / 
Chose  
Chose  
 
 
 
to answer 
 
 
Exit visit 
not to answer 
not to answer 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
 
Rank: 1 = Used most frequent; 2 = Used second most frequent; 3 = Frequently used; 4 = Used a little; 5 = Least used 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.8 
Participant Questionnaire – Part C (Month 1, 2, and 3) 
Safety Population 
 
 
Page 44 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q10 
Q11 
Q11. 
Q12 
Q13 
  Participant ID 
Date 
 
 
 
No 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Put inside the vagina: Xxxxxxx / 
 
Yes / 
Check position of ring / 
 
 
Enrollment / 
No / 
Put inside the underwear/clothing: Xxxxxxx / 
 
No / 
Insert/remove ring / 
 
 
Trial Month XX / 
Chose not  
Tampon / 
 
Chose not  
Insert menses product / 
 
 
Trial Month XX  
to answer 
Sanitary pad / 
 
to answer 
Cleaning / 
 
 
(Unscheduled X) / 
 
Menstrual cup / 
 
 
Sexual pleasure / 
 
 
Exit visit 
 
Water, no soap, inside the vagina / 
 
 
Other: Xxxxxxxxxxx / 
 
 
 
 
Water, with soap, inside the vagina / 
 
 
Chose not to answer 
 
 
 
 
Anything else: Xxxxxxxxxxxx / 
 
 
 
 
 
 
 
Nothing was used / 
 
 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
Rank: 1 = Used most frequent; 2 = Used second most frequent; 3 = Frequently used; 4 = Used a little; 5 = Least used 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.5.9 
Participant Questionnaire – 3 Month Follow-Up 
Safety Population 
 
 
Page 45 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Question 
Question 
No. 
 
 
 
1 
Will you take your extra rings with you today or will you come back to the research centre each month to pick up your new ring? 
2 
What are your reasons for leaving the rings at the research centre today? 
3 
Did you have an additional HIV test at the research centre when you returned to collect your ring (in-between the study visits)? 
4 
Does your main partner know you are in the study and wearing a vaginal ring? 
5 
The research centre staff showed you how to insert and remove your ring. You were also given an instruction sheet that explains this. Was the sheet helpful, or  
 
does it need to be changed? 
6 
Thinking back since your last visit, was it easy or difficult to remove your ring? 
7 
Thinking back since your last visit, when you inserted a new ring, was it easy or difficult? 
8 
You were given a bag(s) to put the used ring in when returning it to the research centre. Please describe your experiences with the bag(s)? 
9 
For those who took extra rings: Where did you store the unused ring(s) before insertion? 
10 
For those who took extra rings: You personally stored the unused rings before using them. What was it like storing the unused ring(s)? 
11 
For those who did not return the used ring to the research centre straight away: Where did you store the used ring(s) after removing it/them? 
12 
For those who did not return the used ring to the research centre straight away: You stored the used ring before bringing it back to the research centre for your  
 
next scheduled visit. What was it like storing the used ring(s)? 
13 
At each regularly scheduled visit, you gave a sample of blood and vaginal fluids. Please tell me what your preferences are. 
14 
Below is a list of things that some women may like about participating in this study (DREAM). Please order these, where 1 means you liked it the most, and 5  
 
means you liked it the least. 
15 
I’m going to read a list of things that some women have experienced during other study/studies. Please tell me if you have experienced any of these things in  
 
this study (DREAM). 
15a 
Length of time spent at the research centre for the study visits was too long. If yes, specify how long. 
15b 
Length of time spent at the research centre to pick up rings was too long. If yes, specify how long. 
15c 
Transport to the research centre for scheduled visits was a problem. If yes, specify. 
15d 
I was treated well when coming to the research centre for regular visits. 
15e 
I was treated well when I came to the research centre to pick up rings. 
15f 
Transport to pick up rings was a problem (if applicable). If yes, specify. 
15g 
If partner knows about participation (see question 4): My partner is happy about my participation in the study. 
15h 
My neighbors, family, or friends know about my participation in this study. If yes, specify if neighbor/friends/family. 
15i 
If neighbor, friends, or family knows about participation (see above): My neighbors, family, or friends (as above) are happy about my participation in this study 
15j 
Other 
16 
If you were not in a study, would you prefer to come to the health care clinic/provider for new rings each month, or every three months? 
17 
If you were not in a study, would you prefer to come to the health care clinic/provider for an HIV test each month, or every three months? 
18 
Do you currently have a main sex partner?  
18a 
How long has he been your partner? 
19 
Do you and your main partner currently live together? 
20 
Have you had any other partners since your last scheduled visit? 


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20a 
If yes, indicate number. 
21 
We need to know how often you usually have sex. Think about the past four weeks, which is about one month. Over the past four weeks, how many rounds of  
 
vaginal sex did you have? 
22 
In the past month, how frequently did you use a male condom during vaginal sex? 
23 
In the past month, how frequently did you use a female condom during vaginal sex? 
24 
During the last round of vaginal sex you had, did you use a condom? 
25 
Since your last scheduled visit, have you had anal sex? 
26 
How worried are you that you might get infected with HIV in the next year? 
27 
Since your last scheduled visit, have you had any menstrual bleeding or any menstrual spotting? 
28 
Since your last scheduled visit, what have you used to control or manage the menstrual blood or spotting? Mark all that apply, using numbers for only those that  
 
apply - with 1 for the item used most, 2 for next most frequent, and so on until least frequent. 
29 
Since your last scheduled visit, has your ring been removed/expelled between scheduled removal dates? 
30 
What was the reason the ring was removed/expelled at this time? 
31 
When the ring was removed/expelled did you clean the ring before reinsertion? 
32 
What did you use to clean the ring when it was removed or expelled? 
33 
Since your last scheduled visit have you inserted your fingers into your vagina for any reason? 
34 
What was the reason for inserting your fingers into your vagina? 
 
 
 
 
 


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IPM 032 
 
 
 
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Participant Questionnaire – 3 Month Follow-Up 
Safety Population 
 
 
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Centre 
Visit 
Visit 
Q1 
Q2 
Q3 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Take them all / 
Do not want anyone to see the rings / 
Yes / 
 
 
Enrollment / 
Collect monthly from centre / 
No private place to keep the unused rings / 
No / 
 
 
Trial Month XX / 
Chose not to answer 
No private place to keep the used rings / 
N/A / 
 
 
Trial Month XX  
 
No appropriate storage place to keep rings / 
Chose not to answer 
 
 
(Unscheduled X) / 
 
No private place to insert the rings / 
 
 
 
Exit visit 
 
Worried I might lose the ring(s) / 
 
 
 
 
 
I might forget to insert the new ring / 
 
 
 
 
 
Like coming to the centre for monthly HIV tests / 
 
 
 
 
 
Like coming to the centre monthly for social reasons / 
 
 
 
 
 
Other: Xxxxxxxxxxxxxxxx / 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’  
 
 
 
 
 
 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


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Safety Population 
 
 
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Centre 
Visit 
Visit 
Q4 
Q5 
Q6 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
He knows about the study and the ring / 
Good as is / 
Easy / 
 
 
Enrollment / 
He only knows that I am in a study / 
Hard to understand / 
Difficult / 
 
 
Trial Month XX / 
He only knows that I am wearing a ring / 
Needs more information: Xxxxxxxxxxxxxxxxx / 
Bit of both / 
 
 
Trial Month XX  
He doesn’t know about the study or the ring / 
Needs to be changed: Xxxxxxxxxxxxxxxxxxx / 
Got easier over 
 
 
(Unscheduled X) / 
Don’t know /  
Did not read the instruction sheet / 
time / 
 
 
Exit visit 
Chose not to answer 
Can’t remember the sheet / 
Neither / 
 
 
 
 
Chose not to answer 
N/A / 
 
 
 
 
 
Chose not  
 
 
 
 
 
to answer 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


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Safety Population 
 
 
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Centre 
Visit 
Visit 
Q7 
Q8 
Q9 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Easy / 
Easy to open and close / 
Bag/handbag / 
 
 
Enrollment / 
Difficult / 
Hard to open or close / 
Shared cupboard/drawer / 
 
 
Trial Month XX / 
Bit of both / 
Was sometimes lost / 
Personal cupboard/drawer / 
 
 
Trial Month XX  
Got easier over 
Used for something else: Xxxxxx / 
Locked place / 
 
 
(Unscheduled X) / 
time / 
Bag was fine / 
At someone else’s house: Xxxxxxx / 
 
 
Exit visit 
Neither / 
Did not like keeping the empty bag(s) / 
Other: Xxxxxxxxxxxx / 
 
 
 
 
Did not like the used ring(s) in the house / 
N/A / 
 
 
 
 
Did not like carrying the used ring(s) to the  
Chose not to answer 
 
 
 
 
research centre / 
 
 
 
 
 
Someone found the ring bag(s): Xxxxxxx / 
 
 
 
 
 
Did not like the look of the bag: Xxxxxxxx / 
 
 
 
 
 
Difficult to bring the bags back to the 
 
 
 
 
 
clinic: Xxxxxxxxxx / 
 
 
 
 
 
Other: Xxxxxxxxxxx / 
 
 
 
 
 
N/A, did not use the bags / 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


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IPM 032 
 
 
 
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Safety Population 
 
 
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Centre 
Visit 
Visit 
Q10 
Q11 
Q12 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
No problems / 
Returned used rings / 
No problems / 
 
 
Enrollment / 
Worried someone might find it / 
Bag/handbag / 
Worried someone might find it / 
 
 
Trial Month XX / 
Forgot where it was stored/lost it / 
Shared cupboard/drawer / 
Forgot where it was stored/lost it / 
 
 
Trial Month XX  
Accidentally threw it away / 
Personal cupboard/drawer / 
Accidentally threw it away / 
 
 
(Unscheduled X) / 
Did not like it: Xxxxxxxxx / 
Locked place / 
Did not like it: Xxxxxxxxx / 
 
 
Exit visit 
Someone found it and it was  
At someone else’s house: Xxxxxxx / 
Someone found it and it was  
 
 
 
a problem: Xxxxxxxxxxx / 
Other: Xxxxxxxxxxxx / 
a problem: Xxxxxxxxxxx / 
 
 
 
Someone found it and it was not 
N/A / 
Someone found it and it was not 
 
 
 
a problem: Xxxxxxxxxxx / 
Chose not to answer 
a problem: Xxxxxxxxxxx / 
 
 
 
Other: Xxxxxxxxx / 
 
Other: Xxxxxxxxx / 
 
 
 
N/A  / 
 
N/A  / 
 
 
 
Chose not to answer 
 
Chose not to answer 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
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Safety Population 
 
 
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Centre 
Visit 
Visit 
Q13: Blood Samples 
Q13: Vaginal Fluid Samples 
Q14: Rank  
Q15 
  Participant 
ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Taken at every visit / 
Taken at every visit / 
Regular HIV testing: X / 
Answered / 
 
 
Enrollment / 
Taken less often / 
Taken less often / 
Other health benefits: X / 
Chose not to answer 
 
 
Trial Month XX / 
N/A / 
N/A / 
Reimbursement money: X / 
 
 
 
Trial Month XX  
Chose not to answer 
Chose not to answer 
Meeting other study participants: X / 
 
 
 
(Unscheduled X) / 
 
 
Helping others in future: X / 
 
 
 
Exit visit 
 
 
Chose not to answer 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
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Safety Population 
 
 
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Centre 
Visit 
Visit 
Q15a 
Q15b 
Q15c 
Q15d 
Q15e 
Q15f 
Q15g 
Q15h 
Q15i 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes: Xxxx / 
Yes: Xxxx / 
Yes: Xxxx / 
Yes / 
Yes / 
Yes: Xxxx / 
Yes / 
Yes: Friends / 
Yes / 
 
 
Enrollment / 
No  
No / 
No  
No / 
No / 
No / 
No / 
Yes: Family / 
No / 
 
 
Trial Month XX / 
 
N/A 
 
 
N/A 
N/A 
N/A 
Yes: Neighbor / 
N/A 
 
 
Trial Month XX  
 
 
 
 
 
 
 
No / 
 
 
 
(Unscheduled X) / 
 
 
 
 
 
 
 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
 
 
 
 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
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Safety Population 
 
 
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Centre 
Visit 
Visit 
Q15j  
Q15j 
Q16 
Q17 
Q18 
Q18a 
  Participant ID 
Date 
 
Experience 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
 
Yes / 
Each month / 
Each month / 
Yes / 
XXX months / 
 
 
Enrollment / 
 
No / 
Every 3 months / 
Every 3 months / 
No / 
XXX years / 
 
 
Trial Month XX / 
 
N/A 
Don’t mind / 
Don’t mind / 
Chose not  
Chose not  
 
 
Trial Month XX  
 
 
Depends: Xxxxxxxxxx / 
Depends: Xxxxxxxxxx / 
to answer 
to answer 
 
 
(Unscheduled X) / 
 
 
Chose not to answer 
Chose not to answer 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
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Safety Population 
 
 
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Centre 
Visit 
Visit 
Q19 
Q20 
Q20a 
Q21 
Q22 
Q23 
Q24 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Yes / 
XXX / 
XXX / 
Always / 
Always / 
Yes male condom / 
 
 
Enrollment / 
No / 
No / 
Chose not  
Chose not to  
Sometimes / 
Sometimes / 
Yes female condom / 
 
 
Trial Month XX / 
Chose not  
Chose not  
to answer 
answer 
Often / 
Often / 
No / 
 
 
Trial Month XX  
to answer 
to answer 
 
 
Never / 
Never / 
Chose not to answer 
 
 
(Unscheduled X) / 
 
 
 
 
Chose not to  
Chose not to  
 
 
 
Exit visit 
 
 
 
 
answer 
answer 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
 
 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
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Safety Population 
 
 
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Centre 
Visit 
Visit 
Q25 
Q25a 
Q26 
Q27 
Q28 
Q28 No. 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Yes / 
Very  / 
Yes / 
Put inside the vagina: Xxxxxxx / 
 
 
 
Enrollment / 
No / 
No / 
A little / 
No / 
Put inside the underwear/clothing: Xxxxxxx / 
 
 
 
Trial Month XX / 
Chose not  Sometimes 
Not at all / 
Chose not  
Tampon / 
 
 
 
Trial Month XX  
to answer 
 
Chose not 
to answer 
Sanitary pad / 
 
 
 
(Unscheduled X) / 
 
 
answer 
 
Menstrual cup / 
 
 
 
Exit visit 
 
 
 
 
Water, no soap, inside the vagina / 
 
 
 
 
 
 
 
 
Water, with soap, inside the vagina / 
 
 
 
 
 
 
 
 
Anything else: Xxxxxxxxxxxx / 
 
 
 
 
 
 
 
 
Nothing was used / 
 
 
 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


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IPM 032 
 
 
 
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Safety Population 
 
 
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Centre 
Visit 
Visit 
Q29 
Q30 
Q31 
Q32 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Removed: Uncomfortable/painful / 
Yes / 
Water only / 
 
 
Enrollment / 
No / 
Removed: Cleaning / 
No / 
Body wash soap only / 
 
 
Trial Month XX / 
Chose not  
Removed: Menses / 
Chose not  
Water and body wash soap / 
 
 
Trial Month XX  
to answer 
Removed: Real/perceived side 
to answer 
Disinfectant: Xxxxxxxxxx / 
 
 
(Unscheduled X) / 
 
effects: Xxxxxxxxxxxxxx / 
 
Herbal product: Xxxxxxxxxx / 
 
 
Exit visit 
 
Removed: Partner request / 
 
Traditional medicine: Xxxxxxx / 
 
 
 
 
Removed: Sex / 
 
Bubble bath: Xxxxxxxxxxxx / 
 
 
 
 
Removed: Keep from partner / 
 
Bath salts: Xxxxxxxxx / 
 
 
 
 
Accident: Xxxxxxxxxxxxxxx / 
 
Dishwashing liquid: Xxxxxxxxx / 
 
 
 
 
Other: Xxxxxxxxxxxxxx / 
 
Other: Xxxxxxxxxxxxxx / 
 
 
 
 
Chose not to answer 
 
Chose not to answer 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


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Safety Population 
 
 
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Centre 
Visit 
Visit 
Q33 
Q34 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Check position of ring / 
 
 
Enrollment / 
No / 
Insert/remove ring / 
 
 
Trial Month XX / 
Chose not to answer 
Insert menses product / 
 
 
Trial Month XX  
 
Cleaning / 
 
 
(Unscheduled X) / 
 
Other: Xxxxxxxxxxx / 
 
 
Exit visit 
 
Sexual pleasure / 
 
 
 
 
Chose not to answer 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.10 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
 
 
Page 58 of 154 
 
Version 1.0 
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Question 
Question 
No. 
 
 
 
1 
When you were doing your three monthly visits, did you take your extra rings with you or did you come back to the research centre each month to pick up your  
 
new ring? 
1a 
If sometimes took them, sometimes left them, did you: 
 
Initially leave it at the centre then later start taking it / 
 
Initially take it then start leaving it at the  
 
centre / 
 
It varied / 
 
Chose not to answer 
2 
What were your reasons for leaving the rings at the research centre? 
3 
Did your main partner know you were in the study and wearing a vaginal ring? 
4 
The research centre staff showed you how to insert and remove your ring. You were also given an instruction sheet that explains this. Was the sheet helpful, or  
 
does it need to be changed? 
5 
Thinking back over the study, when you removed your ring, was it easy or difficult? 
6 
Thinking back, when you inserted your ring, was it easy or difficult? 
7 
You were given a bag(s) to put the used ring in when returning it to the research centre. Please describe your experiences with the bag(s)? 
8 
For those who took extra rings: Over the duration of the study, Where did you store the unused ring(s) before insertion? 
9 
For those who took extra rings: You personally stored the unused rings before using them. What was it like storing the unused ring(s)? 
10 
For those who did not return the used ring to the research centre straight away: During the course of the study where did you store the used ring(s) after  
 
removing it/them? 
11 
For those who did not return the used ring to the research centre straight away: During the course of the study you stored the used ring before bringing it back  
 
to the research centre for your next scheduled visit. What was it like storing the used ring(s)? 
12 
At each regularly scheduled visit, you gave a sample of blood and vaginal fluids. Please tell me what your preferences are. 
13 
Below is a list of things that some women may like about participating in this study (DREAM). Please order these, where 1 means you liked it the most, and 5  
 
means you liked it the least. 
14 
I’m going to read a list of things that some women have experienced during other study/studies. Please tell me if you have experienced any of these things at  
 
any time in this study (DREAM). 
14a 
In general, the length of time spent at the research centre for the study visits was too long. If yes, specify how long. 
14b 
In general, the length of time spent at the research centre to pick up rings was too long. If yes, specify how long. 
14c 
Transport to the research centre for scheduled visits was a problem. If yes, specify. 
14d 
I was treated well when coming to the research centre for regular visits. 
14e 
I was treated well when I came to the research centre to pick up rings. 
14f 
Transport to pick up rings was a problem (if applicable). If yes, specify. 
14g 
If partner knows about participation (see question 3): My partner is happy about my participation in the study. 
14h 
My neighbors, family, or friends know about my participation in this study. If yes, specify if neighbor/friends/family. 


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Safety Population 
 
 
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14i 
If neighbor, friends, or family knows about participation (see above): My neighbors, family, or friends (as above) are happy about my participation in this study. 
14j 
Other, specify 
15 
Please tell us how much you like/do not like participating in this study. 
16 
If you were not in a study, would you prefer to come to the health care clinic/provider for new rings each month, or every three months? 
17 
If you were not in a study, would you prefer to come to the health care clinic/provider for an HIV test each month, or every three months? 
18 
Do you currently have a main sex partner? 
18a 
How long has he been your partner? 
19 
Do you and your main partner currently live together? 
20 
Have you had any other partners since your last scheduled visit? 
20a 
If yes, indicate number. 
21 
We need to know how often you usually have sex. Think about the past four weeks, which is about one month. Over the past four weeks, how many rounds 
 
of vaginal sex did you have? 
22 
In the past month, how frequently did you use a male condom during vaginal sex? 
23 
In the past month, how frequently did you use a female condom during vaginal sex? 
24 
During the last round of vaginal sex you had, did you use a condom? 
25 
Since your last scheduled visit, have you had anal sex? 
25a 
If yes, did you use a condom? 
26 
Since your last scheduled visit, have you had any menstrual bleeding or any menstrual spotting? 
27 
Since your last scheduled visit, what have you used to control or manage the menstrual blood or spotting? Mark all that apply, using numbers for only those that  
 
apply - with 1 for the item used most, 2 for next most frequent, and so on until least frequent. 
28 
Since your last scheduled visit, has your ring been removed/expelled between scheduled removal dates? 
29 
What was the reason the ring was removed/expelled at this time? 
30 
When the ring was removed/expelled did you clean the ring before reinsertion? 
31 
What did you use to clean the ring when it was removed or expelled? 
32 
How worried are you that you might get infected with HIV in the next year? 
33 
Since your last scheduled visit have you inserted your fingers into your vagina for any reason? 
34 
What was the reason for inserting your fingers into your vagina? 
35 
When you first joined the study you were told that we will do tests to see if a woman has been wearing her ring. If a woman was not able to wear her ring as she  
 
is meant to, she was not able to continue to participate in the study. The following tests could be used. Do you think these are good ways to check and make  
 
sure women are using the rings they are given? 
35a 
Test blood to see how much medicine is in the blood. 
35b 
Test used ring to see how much medicine is still in the ring. 
35c 
Ask the woman if she has been using the ring. 
35d 
Other, specify. 
36 
Sometimes women in microbicide studies can’t/don’t always keep their rings inserted. Do you think most women would be more likely to use their rings properly. 
 
if they knew the blood tests or used rings would show staff who was using the ring as intended and who was not? 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.10 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
 
 
Page 60 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
37 
It may be hard for women to use the ring all the time without taking it out. Do you think it is possible for women to use the ring as requested (i.e, without  
 
removing it)? 
38 
What do you think are the most likely reason(s) for a woman to take out her ring? 
39 
Please say whether you strongly agree, agree somewhat or disagree with the following statements below: 
39a 
All women can use the ring without taking it out. 
39b 
Women would need a break from using the ring every few months. 
40 
Do you think women in your community would want to use this ring if it were available? 
41 
If the ring is made available to the public, where do you think most women would want to get it from? 
 
 
42 
If the ring is made available to the public, how much would you be prepared to pay for it? 
43 
If the ring is made available to the public, where do you think it should be marketed/advertised? 
 
 
 
 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.10 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
 
 
Page 61 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q1 
Q1a 
Q2 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Always took it / 
Initially leave it at the centre then later  
Did not want anyone to see the rings / 
 
 
Enrollment / 
Always left it at the centre  
start taking it / 
Did not have a private place to keep the 
 
 
Trial Month XX / 
to collect monthly / 
Initially take it then start leaving it at the  
unused rings / 
 
 
Trial Month XX  
Sometimes took it 
centre / 
Did not have a private place to keep the 
 
 
(Unscheduled X) / 
sometimes left 
It varied: Xxxxxxxxxxxxxxxx / 
used rings / 
 
 
Exit visit 
it at the centre / 
Chose not to answer 
Did not have an appropriate storage place 
 
 
 
Chose not to answer 
 
to keep the rings / 
 
 
 
 
 
Did not have a private place to insert the rings / 
 
 
 
 
 
Worried I might lose the ring(s) / 
 
 
 
 
 
Felt I might forget to insert the new ring if I 
didn’t  
 
 
 
 
 
come each month / 
 
 
 
 
 
Liked coming to the centre for HIV tests each  
 
 
 
 
 
month / 
 
 
 
 
 
Liked coming to the research centre monthly for  
 
 
 
 
 
social reasons / 
 
 
 
 
 
Other: Xxxxxxxxxx / 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
LPUV = Last product use visit 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.10 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
 
 
Page 62 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q3 
Q4 
Q5 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
He knows about the study and the ring / 
Good as is / 
Easy / 
 
 
Enrollment / 
He only knows that I am in a study / 
Hard to understand / 
Difficult / 
 
 
Trial Month XX / 
He only knows that I am wearing a ring / 
Needs more information: Xxxxxxxxxxxxxxx / 
Bit of both / 
 
 
Trial Month XX  
He doesn’t know about the study or the ring / 
Needs to be changed: Xxxxxxxxxxxxxxxxxx / 
Neither / 
 
 
(Unscheduled X) / 
Don’t know / 
Did not read the instruction sheet / 
Got easier over time / 
 
 
Exit visit 
Chose not to answer 
Can’t remember the sheet / 
Neither / 
 
 
 
 
Chose not to answer 
Chose not to answer 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
LPUV = Last product use visit 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.10 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
 
 
Page 63 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q6 
Q7 
Q8 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Easy / 
Easy to open and close / 
Bag/handbag / 
 
 
Enrollment / 
Difficult / 
Hard to open or close / 
Shared cupboard/drawer / 
 
 
Trial Month XX / 
Bit of both / 
Was sometimes lost / 
Personal cupboard/drawer / 
 
 
Trial Month XX  
Neither / 
Used for something else: Xxxxxx / 
Locked place / 
 
 
(Unscheduled X) / 
Got easier over time / 
Bag was fine / 
At someone else’s house: Xxxxxxx / 
 
 
Exit visit 
Neither / 
Did not like keeping the empty bag(s) / 
Other: Xxxxxxxxxxxx / 
 
 
 
Chose not to answer 
Did not like the used ring(s) in the house / 
N/A, did not ever take rings / 
 
 
 
 
Did not like carrying the used ring(s) to the  
Chose not to answer 
 
 
 
 
research centre / 
 
 
 
 
 
Someone found the ring bag(s): Xxxxxxx / 
 
 
 
 
 
Did not like the look of the bag: Xxxxxxxx / 
 
 
 
 
 
Difficult to bring the bags back to the 
 
 
 
 
 
clinic: Xxxxxxxxxx / 
 
 
 
 
 
Other: Xxxxxxxxxxx / 
 
 
 
 
 
N/A, did not use the bags / 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
LPUV = Last product use visit 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.10 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
 
 
Page 64 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q9 
Q10 
Q11 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
No problems / 
Returned used rings / 
No problems / 
 
 
Enrollment / 
Worried someone might find it / 
Bag/handbag / 
Worried someone might find it / 
 
 
Trial Month XX / 
Forgot where it was sorted/lost it / 
Shared cupboard/drawer / 
Forgot where it was sorted/lost it / 
 
 
Trial Month XX  
Accidentally threw it away / 
Personal cupboard/drawer / 
Accidentally threw it away / 
 
 
(Unscheduled X) / 
Did not like it: Xxxxxxxxx / 
Locked place / 
Did not like it: Xxxxxxxxx / 
 
 
Exit visit 
Someone found it and it was  
At someone else’s house: Xxxxxxx / 
Someone found it and it was  
 
 
 
a problem: Xxxxxxxxxxx / 
Other: Xxxxxxxxxxxx / 
a problem: Xxxxxxxxxxx / 
 
 
 
Someone found it and it was not 
N/A, did not store extra rings / 
Someone found it and it was not 
 
 
 
a problem: Xxxxxxxxxxx / 
Chose not to answer 
a problem: Xxxxxxxxxxx / 
 
 
 
Other: Xxxxxxxxx / 
 
Other: Xxxxxxxxx / 
 
 
 
N/A, did not ever take extra rings / 
 
N/A, did not have/store extra rings / 
 
 
 
Chose not to answer 
 
Chose not to answer 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
LPUV = Last product use visit 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.10 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
 
 
Page 65 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q12: Blood Samples 
Q12: Vaginal Fluid Sample 
Q13: Rank  
Q14 
Q14a 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Taken at every visit / 
Taken at every visit / 
Regular HIV testing: X / 
Answered / 
Yes: Xxxx / 
 
 
Enrollment / 
Taken less often / 
Taken less often / 
Other health benefits: X / 
Chose not to  
No  
 
 
Trial Month XX / 
N/A / 
N/A / 
Reimbursement money: X / 
answer 
 
 
 
Trial Month XX  
Chose not to answer 
Chose not to answer 
Meeting other participants: X / 
 
 
 
 
(Unscheduled X) / 
 
 
Chose not to answer 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
LPUV = Last product use visit 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.10 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
 
 
Page 66 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q14b 
Q14c 
Q14d 
Q14e 
Q14f 
Q14g 
Q14h 
Q14i 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes: Xxxx / 
Yes: Xxxx / 
Yes / 
Yes / 
Yes: Xxxx / 
Yes / 
Yes: Family / 
Yes/ 
 
 
Enrollment / 
No / 
No  
No / 
No / 
No / 
No / 
Yes: Friends / 
No / 
 
 
Trial Month XX / 
N/A 
 
 
N/A 
N/A 
N/A 
Yes: Neighbor / 
N/A 
 
 
Trial Month XX  
 
 
 
 
 
 
No 
 
 
 
(Unscheduled X) / 
 
 
 
 
 
 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
 
 
 
LPUV = Last product use visit 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.10 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
 
 
Page 67 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q14j  
Q14j 
Q15 
Q16 
Q17 
  Participant ID 
Date 
 
Experience 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Xxxxxxxxxxx 
Yes / 
Don’t like it: Xxxxxxxxxxx / 
Each month / 
Each month / 
 
 
Enrollment / 
 
No / 
It’s alright/okay / 
Every 3 months / 
Every 3 months / 
 
 
Trial Month XX / 
 
N/A 
Really liked it: Xxxxxxxxxxxxx / 
Don’t mind / 
Don’t mind / 
 
 
Trial Month XX  
 
 
Other: Xxxxxxxxxxxxxxxxxx / 
Depends: Xxxxxxxxx / 
Depends: Xxxxxxxxx / 
 
 
(Unscheduled X) / 
 
 
Chose not to answer 
Chose not to answer 
Chose not to answer 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LPUV = Last product use visit 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.10 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
 
 
Page 68 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q18 
Q18a 
Q19 
Q20 
Q20a 
Q21 
Q22 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
XXX months / 
Yes / 
Yes / 
XXX / 
XXX / 
Always / 
 
 
Enrollment / 
No / 
XXX years / 
No / 
No / 
Chose not  
Chose not to  
Sometimes / 
 
 
Trial Month XX / 
Chose not  
Chose not  
Chose not  
Chose not  
to answer 
answer 
Often / 
 
 
Trial Month XX  
to answer 
to answer 
to answer 
to answer 
 
 
Never / 
 
 
(Unscheduled X) / 
 
 
 
 
 
 
Chose not to  
 
 
Exit visit 
 
 
 
 
 
 
answer 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
 
 
LPUV = Last product use visit 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.10 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
 
 
Page 69 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q23 
Q24 
Q25 
Q26 
Q27 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Always / 
Yes male condom / 
Yes / 
Yes / 
Put inside the vagina: Xxxxxxx / 
 
 
Enrollment / 
Sometimes / 
Yes female condom / 
No / 
No / 
Put inside the underwear/clothing: Xxxxxxx / 
 
 
Trial Month XX / 
Often / 
No / 
Chose not  
Chose not  
Tampon / 
 
 
Trial Month XX  
Never / 
Chose not to answer 
to answer 
to answer 
Sanitary pad / 
 
 
(Unscheduled X) / 
Chose not  
 
 
 
Menstrual cup / 
 
 
Exit visit 
to answer 
 
 
 
Water, no soap, inside the vagina / 
 
 
 
 
 
 
 
Water, with soap, inside the vagina / 
 
 
 
 
 
 
 
Anything else: Xxxxxxxxxxxx / 
 
 
 
 
 
 
 
Nothing was used / 
 
 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
LPUV = Last product use visit 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.10 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
 
 
Page 70 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q27  
Q28 
Q29 
Q30 
Q31 
  Participant ID 
Date 
 
No. 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
 
Yes / 
Removed: Uncomfortable/painful / 
Yes / 
Water only / 
 
 
Enrollment / 
 
No / 
Removed: Cleaning / 
No / 
Body wash soap only / 
 
 
Trial Month XX / 
 
Chose not  
Removed: Menses / 
Chose not  
Water and body wash soap / 
 
 
Trial Month XX  
 
to answer 
Removed: Real/perceived side  
to answer 
Disinfectant: Xxxxxxxxxx / 
 
 
(Unscheduled X) / 
 
 
effects: Xxxxxxxxxxxxxx / 
 
Herbal product: Xxxxxxxxxx / 
 
 
Exit visit 
 
 
Removed: Partner request / 
 
Traditional medicine: Xxxxxxx / 
 
 
 
 
 
Removed: Sex / 
 
Bubble bath: Xxxxxxxxxx / 
 
 
 
 
 
Removed: Keep from partner / 
 
Bath salts: Xxxxxxxxx / 
 
 
 
 
 
Accident: Xxxxxxxxxxxxxxx / 
 
Dishwashing liquid: Xxxxxxxxx / 
 
 
 
 
 
Other: Xxxxxxxxxxxxxx / 
 
Other: Xxxxxxxxxxxxxx / 
 
 
 
 
 
Chose not to answer 
 
Chose not to answer 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
LPUV = Last product use visit 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.10 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
 
 
Page 71 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q32 
Q33 
Q34 
Q35 
Q35a 
Q35b 
Q35c 
Q35d  
  Participant ID 
Date 
 
 
 
 
 
 
 
 
Specify 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Very / 
Yes / 
Check position of ring / 
Answered / 
Yes / 
Yes / 
Yes / 
 
 
 
Enrollment / 
A little / 
No / 
Insert/remove ring / 
Not answered 
No 
No 
No 
 
 
 
Trial Month XX / 
Not at all 
Chose not 
Insert menses product / 
 
 
 
 
 
 
 
Trial Month XX  
 
to answer 
Cleaning / 
 
 
 
 
 
 
 
(Unscheduled X) / 
 
 
Sexual pleasure / 
 
 
 
 
 
 
 
Exit visit 
 
 
Other: Xxxxxxxxxxx / 
 
 
 
 
 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
 
 
 
LPUV = Last product use visit 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.10 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
 
 
Page 72 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q35d 
Q36 
Q37 
Q38 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Yes / 
Yes / 
Partner request / 
 
 
Enrollment / 
No 
No: Xxxxxxxxxx / 
No: Xxxxxxxxxx / 
Fear of partner feeling it / 
 
 
Trial Month XX / 
 
Don’t know: Xxxxxxxxx / 
Don’t know: Xxxxxxxxx / 
Influence of others: Xxxxxxxxx / 
 
 
Trial Month XX  
 
Chose not to answer 
Chose not to answer 
Break from having the ring inside / 
 
 
(Unscheduled X) / 
 
 
 
Mense / 
 
 
Exit visit 
 
 
 
Side effects / 
 
 
 
 
 
 
Discomfort/pain / 
 
 
 
 
 
 
Belief that ring doesn’t work / 
 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
LPUV = Last product use visit 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.10 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
 
 
Page 73 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q39a 
Q39b 
Q40 
Q41 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Strongly agree / 
Strongly agree / 
Yes / 
Clinic / 
 
 
Enrollment / 
Somewhat agree / 
Somewhat agree / 
No: Xxxxxxxxxx / 
Pharmacy / 
 
 
Trial Month XX / 
Strongly disagree / 
Strongly disagree / 
Chose not to answer 
Private doctor / 
 
 
Trial Month XX  
Chose not to answer / 
Chose not to answer 
 
Other: Xxxxxx / 
 
 
(Unscheduled X) / 
 
 
 
Wouldn’t want to wear it / 
 
 
Exit visit 
 
 
 
Chose not to answer 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
LPUV = Last product use visit 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.10 
Participant Questionnaire – Last Product Use Visit 
Safety Population 
 
 
Page 74 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Q42 
Q43 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Free / 
Qualified healthcare providers / 
 
 
Enrollment / 
Would pay: ZARXXXX / 
Local clinic/hospital notice boards / 
 
 
Trial Month XX / 
Would pay: UShXXXX / 
Pamphlets in clinics only / 
 
 
Trial Month XX  
Chose not to answer 
Pamphlets in pharmacies/private doctor / 
 
 
(Unscheduled X) / 
 
Pamphlets in public areas: Xxxxxxxxxxxxxx / 
 
 
Exit visit 
 
Television and/or radio / 
 
 
 
 
Billboards / 
 
 
 
 
Other: Xxxxxxxxx / 
 
 
 
 
 Chose not to answer 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
LPUV = Last product use visit 
Rank: 1 = Liked the most; 2 = Liked second most; 3 = Liked; 4 = Liked a little; 5 = Liked the least 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.11 
Feasibility of a 3-Monthly Clinical Follow-Up Schedule 
Safety Population 
 
 
Page 75 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Participant 
Question 
Question 
Questionnaire 
No. 
 
 
 
 
Part A 
1 
As per investigator decision, are you coming to the research centre next month or in three months for your next visit? 
 
2 
Will you take your extra ring with you today or will you come back to the research centre each month to pick up your new ring? 
 
3 
What are your reasons for leaving the rings at the research centre today? 
 
 
 
Part B 
10 
If you were not in a study, would you prefer to come to the health care clinic / provider for new rings each month, or every three months? 
 
11 
If you were not in a study, would you prefer to come to the health care clinic / provider for an HIV test each month, or every three months? 
 
 
 
3 Month Follow-up 
1 
Will you take your extra rings with you today or will you come back to the research centre each month to pick up your new ring? 
 
2 
What are your reasons for leaving the rings at the research centre today? 
 
16 
If you were not in a study, would you prefer to come to the health care clinic / provider for new rings each month, or every three months? 
 
17 
If you were not in a study, would you prefer to come to the health care clinic / provider for an HIV test each month, or every three months? 
 
 
 
LPUV 
1 
When you were doing your three monthly visits, did you take your extra rings with you or did you come back to the research centre each  
 
 
month to pick up your new ring? 
 
1a 
If sometimes took them, sometimes left them, did you: 
 
 
Initially leave them at the research centre then later start taking them / 
 
 
Initially take them, then start leaving them at the research centre / 
 
 
It varied / 
 
 
Chose not to answer 
 
2 
What were your reasons for leaving the rings at the research centre? 
 
16 
If you were not in a study, would you prefer to come to the health care clinic / provider for new rings each month, or every three months? 
 
17 
If you were not in a study, would you prefer to come to the health care clinic / provider for an HIV test each month, or every three months? 
 
 
 
 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.11 
Feasibility of a 3-Monthly Clinical Follow-Up Schedule 
Safety Population 
 
 
Page 76 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
Part A (Month 1, 2 and 3) 
Centre 
Visit 
Visit 
Q1 
Q2 
Q3 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Next month / 
Will take them all / 
Do not want anyone to see rings / 
 
 
Enrollment / 
In three months 
Will leave them at the 
research 
Do not have a private place to keep unused rings at home / 
 
 
Trial Month XX / 
 
centre to collect monthly / 
Do not have a private place to keep the used rings at home / 
 
 
Trial Month XX  
 
Chose not to answer 
Do not have an appropriate storage place to keep the rings 
 
 
(Unscheduled X) / 
 
 
(used and unused) at home / 
 
 
Exit visit 
 
 
Do not have a private place to insert the rings at home / 
 
 
 
 
 
Worried I might lose the ring(s) / 
 
 
 
 
 
Feel I might forget to insert the new ring if I don’t come each month 
/ 
 
 
 
 
 
Like coming to the research centre for HIV tests each month / 
 
 
 
 
 
Like coming to the research centre monthly for social reasons / 
 
 
 
 
 
Other: Xxxxxxxxxxxxxxxx / 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
LPUV = Last product use visit 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.11 
Feasibility of a 3-Monthly Clinical Follow-Up Schedule 
Safety Population 
 
 
Page 77 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
Part B (Month 2 and 3 Only) 
 
3 Month Follow-up 
Centre 
Visit 
Visit 
Q10 
Q11 
 
Q1 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Each month / 
Each month / 
 
Will take them all / 
 
 
Enrollment / 
Every three months / 
Every three months / 
 
Will leave them at the research centre to collect monthly 
/ 
 
 
Trial Month XX / 
Don’t mind / 
Don’t mind / 
 
Chose not to answer 
 
 
Trial Month XX  
Depends (e.g. if working): 
Depends (e.g. if working): 
 
 
 
 
(Unscheduled X) / 
Xxxxxxxxxxxxxxxxxxx / 
Xxxxxxxxxxxxxxxxxxx / 
 
 
 
 
Exit visit 
Chose not to answer 
Chose not to answer 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
LPUV = Last product use visit 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.11 
Feasibility of a 3-Monthly Clinical Follow-Up Schedule 
Safety Population 
 
 
Page 78 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
3 Month Follow-up 
Centre 
Visit 
Visit 
Q2 
Q16 
Q17 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Do not want anyone to see rings / 
Each month / 
Each month / 
 
 
Enrollment / 
Do not have a private place to keep unused rings at home / 
Every three months / 
Every three months / 
 
 
Trial Month XX / 
Do not have a private place to keep the used rings at home / 
Don’t mind / 
Don’t mind / 
 
 
Trial Month XX  
Do not have an appropriate storage place to keep the rings 
Depends (e.g. if working): 
Depends (e.g. if working): 
 
 
(Unscheduled X) / 
(used and unused) at home / 
Xxxxxxxxxxxxxxxxxxx / 
Xxxxxxxxxxxxxxxxxxx / 
 
 
Exit visit 
Do not have a private place to insert the rings at home / 
Chose not to answer 
Chose not to answer 
 
 
 
Worried I might lose the ring(s) / 
 
 
 
 
 
Feel I might forget to insert the new ring if I don’t come each  
 
 
 
 
 
month / 
 
 
 
 
 
Like coming to the research centre for HIV tests each month / 
 
 
 
 
 
Like coming to the research centre monthly for social reasons 
/ 
 
 
 
 
 
Other: Xxxxxxxxxxxxxxxx / 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
LPUV = Last product use visit 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.11 
Feasibility of a 3-Monthly Clinical Follow-Up Schedule 
Safety Population 
 
 
Page 79 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
LPUV 
Centre 
Visit 
Visit 
Q1 
Q1a 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Always took them / 
Initially leave them at the research centre then later start 
 
 
Enrollment / 
Always left the research centre to collect monthly 
/ 
taking them / 
 
 
Trial Month XX / 
Sometimes took them, sometimes left them at 
Initially take them, then start leaving them at the research centre / 
 
 
Trial Month XX  
the research centre/ 
It varied: Xxxxxxxxxxxxxxxxxxxxxxxxxxxx / 
 
 
(Unscheduled X) / 
Chose not to answer 
Chose not to answer 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
LPUV = Last product use visit 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.11 
Feasibility of a 3-Monthly Clinical Follow-Up Schedule 
Safety Population 
 
 
Page 80 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
LPUV 
Centre 
Visit 
Visit 
Q2 
Q16 
Q17 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Did not want anyone to see the rings / 
Each month / 
Each month / 
 
 
Enrollment / 
Did not have a private place to keep the unused 
Every three months / 
Every three months / 
 
 
Trial Month XX / 
rings / 
Don’t mind / 
Don’t mind / 
 
 
Trial Month XX  
Did not have a private place to keep the used 
Depends (e.g. if working): 
Depends (e.g. if working): 
 
 
(Unscheduled X) / 
rings / 
Xxxxxxxxxxxxxxxxxxx / 
Xxxxxxxxxxxxxxxxxxx / 
 
 
Exit visit 
Did not have an appropriate storage place to 
keep 
Chose not to answer 
Chose not to answer 
 
 
 
the rings (used or unused) at home / 
 
 
 
 
 
Did not have a private place to insert the rings at 
 
 
 
 
 
home / 
 
 
 
 
 
Worried I might lose the ring(s) / 
 
 
 
 
 
Felt I might forget to insert the new ring if I didn’t 
 
 
 
 
 
come each month / 
 
 
 
 
 
Liked coming to the research centre monthly for 
 
 
 
 
 
social reasons / 
 
 
 
 
 
Other: Xxxxxxxxxxxxxxxxxxxxxxxxxx / 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
LPUV = Last product use visit 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.12 
Participant Questionnaire – Vaginal Practices 
Safety Population 
 
 
Page 81 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
External Cleaning/ External Genital Washing 
Centre 
Visit  
Visit 
Done 
Product(s) Used 
Product(s) 
Removed  Reason for Product 
  Participant ID 
Date 
 
 
 
Applied Using 
Ring 
Use 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Water only / 
Cloth / 
Yes / 
General cleaning/hygiene / 
 
 
Trial Month XX / 
No / 
Soap only: Xxxxxxx / 
Hands / 
No 
Cleaning/hygiene during menses / 
 
 
Trial Month XX  
Chose not  
Soap and water / 
Other: Xxxxx / 
 
To clean for sex / 
 
 
(Unscheduled X) / 
to answer 
Disinfectant/detergent: Xxxxxxx / 
 
 
To clean after sex / 
 
 
Exit visit 
 
Traditional: Xxxxxxxx / 
 
 
Prepare vagina for sexual pleasure / 
 
 
 
 
Other: Xxxxxxxx  
 
 
Improve/enhance sex / 
 
 
 
 
 
 
 
Dry/tighten vagina / 
 
 
 
 
 
 
 
Heal/treat vagina / 
 
 
 
 
 
 
 
Other: Xxxxxxxxxxxx / 
 
 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.12 
Participant Questionnaire – Vaginal Practices 
Safety Population 
 
 
Page 82 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
Internal Cleaning/ Internal Vaginal Cleansing 
Centre 
Visit  
Visit 
Done 
Product(s) Used 
Product(s) 
Removed  Reason for Product 
  Participant ID 
Date 
 
 
 
Applied Using 
Ring 
Use 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Water only / 
Cloth / 
Yes / 
General cleaning/hygiene / 
 
 
Trial Month XX / 
No / 
Soap only: Xxxxxxx / 
Hands / 
No 
Cleaning/hygiene during menses / 
 
 
Trial Month XX  
Chose not  
Soap and water / 
Other: Xxxxx / 
 
To clean for sex / 
 
 
(Unscheduled X) / 
to answer 
Disinfectant/detergent: Xxxxxxx / 
 
 
To clean after sex / 
 
 
Exit visit 
 
Traditional: Xxxxxxxx / 
 
 
Prepare vagina for sexual pleasure / 
 
 
 
 
Gels: Xxxxxxxxxxx / 
 
 
Improve/enhance sex / 
 
 
 
 
Other: Xxxxxxxx 
 
 
Dry/tighten vagina / 
 
 
 
 
 
 
 
Heal/treat vagina / 
 
 
 
 
 
 
 
Other: Xxxxxxxxxxxx / 
 
 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.12 
Participant Questionnaire – Vaginal Practices 
Safety Population 
 
 
Page 83 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
Vaginal Steaming/ Smoking 
Centre 
Visit  
Visit 
Done 
Product(s) Used 
Product(s) 
Removed  Reason for Product 
  Participant ID 
Date 
 
 
 
Applied Using 
Ring 
Use 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Traditional: Xxxxxxxx / 
Cloth / 
Yes / 
General cleaning/hygiene / 
 
 
Trial Month XX / 
No / 
Commercial: Xxxxxxxxxx / 
Hands / 
No 
Cleaning/hygiene during menses / 
 
 
Trial Month XX  
Chose not  
Other: Xxxxxxxx 
Other: Xxxxx / 
 
To clean for sex / 
 
 
(Unscheduled X) / 
to answer 
 
 
 
To clean after sex / 
 
 
Exit visit 
 
 
 
 
Prepare vagina for sexual pleasure / 
 
 
 
 
 
 
 
Improve/enhance sex / 
 
 
 
 
 
 
 
Dry/tighten vagina / 
 
 
 
 
 
 
 
Heal/treat vagina / 
 
 
 
 
 
 
 
Other: Xxxxxxxxxxxx / 
 
 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.12 
Participant Questionnaire – Vaginal Practices 
Safety Population 
 
 
Page 84 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
Inserted Products Into Vagina 
Centre 
Visit  
Visit 
Done 
Product(s) Used 
Product(s) 
Removed  Reason for Product 
  Participant ID 
Date 
 
 
 
Applied Using 
Ring 
Use 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Tampon / 
Cloth / 
Yes / 
General cleaning/hygiene / 
 
 
Trial Month XX / 
No / 
Cloth / 
Hands / 
No 
Cleaning/hygiene during menses / 
 
 
Trial Month XX  
Chose not  
Type of paper: Xxxxxxxx / 
Other: Xxxxx / 
 
To clean for sex / 
 
 
(Unscheduled X) / 
to answer 
Cotton wool / 
 
 
To clean after sex / 
 
 
Exit visit 
 
Snuff, Kuber: Xxxxxxxxxx / 
 
 
Prepare vagina for sexual pleasure / 
 
 
 
 
Zambuk / 
 
 
Improve/enhance sex / 
 
 
 
 
Talc / 
 
 
Dry/tighten vagina / 
 
 
 
 
Other commercial: Xxxxxxxxx / 
 
 
Heal/treat vagina / 
 
 
 
 
Traditional: Xxxxxx / 
 
 
Other: Xxxxxxxxxxxx / 
 
 
 
 
Other: Xxxxxxxxxxxxxx 
 
 
Chose not to answer 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.12 
Participant Questionnaire – Vaginal Practices 
Safety Population 
 
 
Page 85 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
External Application 
Centre 
Visit  
Visit 
Done 
Product(s) Used 
Product(s) 
Removed  Reason for Product 
  Participant ID 
Date 
 
 
 
Applied Using 
Ring 
Use 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Commercial cream: Xxxxxxxx / 
Cloth / 
Yes / 
General cleaning/hygiene / 
 
 
Trial Month XX / 
No / 
Talc / 
Hands / 
No 
Cleaning/hygiene during menses / 
 
 
Trial Month XX  
Chose not  
Intimate sprays / 
Other: Xxxxx / 
 
To clean for sex / 
 
 
(Unscheduled X) / 
to answer 
Traditional: Xxxxxxxx / 
 
 
To clean after sex / 
 
 
Exit visit 
 
Other: Xxxxxxxx 
 
 
Prepare vagina for sexual pleasure / 
 
 
 
 
 
 
 
Improve/enhance sex / 
 
 
 
 
 
 
 
Dry/tighten vagina / 
 
 
 
 
 
 
 
Heal/treat vagina / 
 
 
 
 
 
 
 
Other: Xxxxxxxxxxxx / 
 
 
 
 
 
 
 
Chose not to answer 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.13 
Dapivirine Concentration Sample Collection 
Safety Population 
 
 
Page 86 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Plasma Sample for 
Vaginal Fluid Sample for 
Wet Tear Test  
Dry Tear Test 
  Participant ID 
Date 
 
Dapivirine Concentration 
Dapivirine Concentration 
Strip Mass (g) 
Strip Mass (g) 
 
 
 
Collected 
Collected 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Yes / 
XX.XXXX 
XX.XXXX 
 
 
Enrollment / 
No: Xxxxxxxxxxxx 
No: Xxxxxxxxxxxx 
 
 
 
 
Trial Month XX / 
 
 
 
 
 
 
Trial Month XX (Unscheduled X) / 
 
 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.13 
Dapivirine Concentration Sample Collection 
Safety Population 
 
 
Page 87 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Visit 
Sample Mass (g) 
Comments 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
XX.XXXX 
 
 
 
Enrollment / 
 
 
 
 
Trial Month XX / 
 
 
 
 
Trial Month XX (Unscheduled X) / 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.14 
Dapivirine Ring Residual Levels (mg) in the Last Three Returned Rings Prior to HIV-1 Seroconversion 
m-ITT Population 
 
 
Page 88 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Participant ID 
Day of HIV-1 
Visit 
Residual  
Appearance of  
Color of Ring 
Average Residual Levels of  
IPM 027  
 
Seroconversion 
 
Dapivirine 
Ring 
 
HIV-Neg. Participants Over the  Treatment 
 
 
 
in Ring (mg) 
 
 
Duration of the Trial 
 
 
 
 
 
 
 
 
 
XXXXXXXX 
XX 
Trial Month XX 
XX 
Appears used:  
White to off-white 
XX.X 
Dapivirine / 
 
 
 
 
Xxxxxxxx / 
cream-colored / 
 
Placebo 
 
 
 
 
Appears not used:  
Slight yellow to  
 
 
 
 
 
 
Xxxxx / 
yellow / 
 
 
 
 
 
 
Not sure:  
Tan / 
 
 
 
 
 
 
Xxxxxxxxx 
Brown / 
 
 
 
 
 
 
 
Other color:  
 
 
 
 
 
 
 
Xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1; RNA = Ribonucleic acid 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.5.15 
Dapivirine Concentration in the Last Two Returned Rings Prior to First Positive HIV RNA PCR Test 
m-ITT Population 
 
 
Page 89 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Participant 
Date of  
Day of  
Ring  Residual Dapivirine  
Appearance of  
Color of Ring 
Average Residual Levels of  
IPM 027 
ID 
HIV-1 RNA 
HIV-1 RNA 
No. 
in Ring (mg)  
Ring 
 
HIV-Neg. Participants Over the  
Treatment 
 
Detection 
Detection 
 
 
 
 
Duration of the Trial 
 
 
 
 
 
 
 
 
 
 
XXXXXXXX 
ddMMMyyyy 
XX 
XX 
XX 
Appears used:  
White to off-white 
XX 
Dapivirine / 
 
 
 
 
 
Xxxxxxxx / 
cream-colored / 
 
Placebo 
 
 
 
 
 
Appears not used:  
Slight yellow to  
 
 
 
 
 
 
 
Xxxxx / 
yellow / 
 
 
 
 
 
 
 
Not sure:  
Tan / 
 
 
 
 
 
 
 
Xxxxxxxxx 
Brown / 
 
 
 
 
 
 
 
 
Other color:  
 
 
 
 
 
 
 
 
Xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1; RNA = Ribonucleic acid 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.7.1 
Treatment Emergent Adverse Events 
Safety Population 
 
 
Page 90 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
Start Date 
End Date 
Study Day  
Duration of 
Related  
Worsening 
Severity  
SAE? 
  Participant ID 
Preferred Term / 
 
 
of Start 
AE  (Days) 
to IP 
of Pre-Existing 
Grade 
 
 
AE Term (Verbatim) 
 
 
of AE  
 
 
Condition? 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
   XXXXXXXX 
 
ddMMMyyyy 
ddMMMyyyy / 
XXX 
XX / 
Yes / 
Yes / 
1 / 
Yes / 
 
 
 
Ongoing 
 
> XX 
No 
No 
2 / 
No 
 
 
 
 
 
 
 
 
3 / 
 
 
 
 
 
 
 
 
 
4 / 
 
 
 
 
 
 
 
 
 
5 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- List all CMs captured, separated with a ; 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Duration of ring removal = Date re-introduced – Date withdrawn+1  
- Concatenate SOC, PT and AE Term separated by ‘/’  
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; CM = Concomitant medication; IP = Investigational product; SAE = Serious adverse event; SPL = Surgical intervention/procedure log  
Severity grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death  
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.7.1 
Treatment Emergent Adverse Events 
Safety Population 
 
 
Page 91 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
IPM 027 
Action Taken 
Date IP 
Duration of  
Other Action Taken: 
Procedures 
  Participant ID 
Preferred Term / 
Treatment 
with IP 
Withdrawn 
Ring Removal  
CM Name 
Performed / 
 
AE Term (Verbatim) 
 
 
 
(Days) 
 
SPL Page No. 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
 
Dapivirine / 
Dose not changed / 
ddMMMyyyy 
XX 
None / 
Yes: XX / 
 
 
Placebo 
Drug interrupted / 
 
 
Treatment medication: 
Xxxxxx  / 
No 
 
 
 
Drug withdrawn / 
 
 
Non-drug therapy / 
 
 
 
 
Not applicable 
 
 
Other: Xxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- List all CMs captured, separated with a ; 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Duration of ring removal = Date re-introduced – Date withdrawn+1  
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
 
 
AE = Adverse event; CM = Concomitant medication; IP = Investigational product; SAE = Serious adverse event; SPL = Surgical intervention/procedure log  
Severity grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death  
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.7.1 
Treatment Emergent Adverse Events 
Safety Population 
 
 
Page 92 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
Outcome 
Comments 
  Participant ID 
Preferred Term / 
 
 
 
AE Term (Verbatim) 
 
 
 
 
 
 
Centre XX 
 
 
 
   XXXXXXXX 
 
Fatal / 
 
 
 
Unknown / 
 
 
 
Not recovered/not resolved / 
 
 
 
Recovering/resolving / 
 
 
 
Recovered/resolved / 
 
 
 
Recovered/resolved with 
 
 
 
sequelae: Xxxxxxxxxxxxxxxxxx 
 
 
 
 
 
Programmers Notes: 
- List all CMs captured, separated with a ; 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Duration of ring removal = Date re-introduced – Date withdrawn+1  
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
AE = Adverse event; CM = Concomitant medication; IP = Investigational product; SAE = Serious adverse event SPL = Surgical intervention/procedure log  
Severity grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death  
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
 Listing 16.2.7.2 
Product-Related Treatment Emergent Adverse Events 
Safety Population 
 
 
Page 93 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
Start Date 
End Date 
Study Day of 
Duration of 
Severity 
SAE? 
IPM 027 
  Participant ID 
Preferred Term / 
 
 
Start of AE 
AE (Days) 
Grade 
 
Treatment 
 
AE Term (Verbatim) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
   XXXXXXXX 
 
ddMMMyyyy 
ddMMMyyyy / 
XXX 
XX / 
1 / 
Yes / 
Dapivirine / 
 
 
 
Ongoing 
 
> XX 
2 / 
No 
Placebo 
 
 
 
 
 
 
3 / 
 
 
 
 
 
 
 
 
4 / 
 
 
 
 
 
 
 
 
5 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Duration of ring removal = Date re-introduced – Date withdrawn+1  
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
Severity grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
 Listing 16.2.7.2 
Product-Related Treatment Emergent Adverse Events 
Safety Population 
 
 
Page 94 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
Action Taken with  
Date IP 
Duration of  
Other Action 
Outcome 
Comments 
  Participant ID 
Preferred Term / 
IP 
Withdrawn 
Ring Removal  Taken 
 
 
 
AE Term (Verbatim) 
 
 
(Days) 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
 
Dose not changed / 
ddMMMyyyy 
XX 
None / 
Fatal / 
 
 
 
Drug interrupted / 
 
 
Treatment 
medication: 
Not recovered/ not 
resolved / 
 
 
 
Drug withdrawn / 
 
 
Xxxxxxxxx / 
Unknown / 
 
 
 
Not applicable 
 
 
Non-drug 
therapy / 
Recovering/ 
resolving / 
 
 
 
 
 
 
Other: 
Xxxxxxxxx 
Recovered/ 
resolved / 
 
 
 
 
 
 
 
Recovered/ 
resolved with 
 
 
 
 
 
 
 
sequelae: 
Xxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Duration of ring removal = Date re-introduced – Date withdrawn+1  
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
Severity grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
 Listing 16.2.7.3 
Treatment Emergent Adverse Events Leading to Temporary Product Discontinuation 
Safety Population 
 
 
Page 95 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
Start Date 
End Date 
Study Day of 
Duration of 
Related  
Severity 
SAE? 
  Participant ID 
Preferred Term / 
 
 
Start of AE 
AE (Days) 
to IP 
Grade 
 
 
AE Term (Verbatim) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
   XXXXXXXX 
 
ddMMMyyyy 
ddMMMyyyy / 
XXX 
XX / 
Yes / 
1 / 
Yes / 
 
 
 
Ongoing 
 
> XX 
No 
2 / 
No 
 
 
 
 
 
 
 
3 / 
 
 
 
 
 
 
 
 
4 / 
 
 
 
 
 
 
 
 
5  
 
 
 
 
 
 
 
 
 
 
Programmers Notes:  
- Source: A participant reported as having an AE with an action taken of “drug interrupted” per the AE CRF 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
Severity grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
 Listing 16.2.7.3 
Treatment Emergent Adverse Events Leading to Temporary Product Discontinuation 
Safety Population 
 
 
Page 96 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
IPM 027 
Action Taken 
Duration of 
Other Action Taken 
Outcome 
  Participant ID 
Preferred Term / 
Treatment 
with IP 
Ring Removal 
 
 
 
AE Term (Verbatim) 
 
 
(Days) 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
 
Dapivirine / 
Drug interrupted  XX 
None / 
Fatal / 
 
 
Placebo 
 
 
Treatment medication:  
Unknown / 
 
 
 
 
 
Xxxxxxx  / 
Not recovered/not resolved / 
 
 
 
 
 
Non-drug therapy / 
Recovering/resolving / 
 
 
 
 
 
Other: Xxxxxxxxx 
Recovered/resolved / 
 
 
 
 
 
 
Recovered/resolved with 
 
 
 
 
 
 
sequelae: Xxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
Programmers Notes: 
- Source: A participant reported as having an AE with an action taken of “drug interrupted” per the AE CRF 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
Severity grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
 Listing 16.2.7.4 
Treatment Emergent Adverse Events Leading to Permanent Product Discontinuation 
Safety Population 
 
 
Page 97 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
Start Date 
End Date 
Study Day of 
Duration of 
Related  
Severity 
SAE? 
  Participant ID 
Preferred Term / 
 
 
Start of AE 
AE (Days) 
to IP 
Grade 
 
 
AE Term (Verbatim) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
   XXXXXXXX 
 
ddMMMyyyy 
ddMMMyyyy / 
XXX 
XX / 
Yes / 
1 / 
Yes / 
 
 
 
Ongoing 
 
> XX 
No 
2 / 
No 
 
 
 
 
 
 
 
3 / 
 
 
 
 
 
 
 
 
4 / 
 
 
 
 
 
 
 
 
5  
 
 
 
 
 
 
 
 
 
 
Programmers Notes:  
- Source: A participant reported as having an AE with an action taken of “drug withdrawn” per the AE CRF 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
Severity grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death  
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 
 
 


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IPM 032 
 
 
 
 Listing 16.2.7.4 
Treatment Emergent Adverse Events Leading to Permanent Product Discontinuation 
Safety Population 
 
 
Page 98 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
IPM 027 
Action Taken 
Date IP 
Other Action Taken 
Outcome 
  Participant ID 
Preferred Term / 
Treatment 
with IP 
Withdrawn  
 
 
 
AE Term (Verbatim) 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
 
Dapivirine / 
Drug withdrawn 
ddMMMyyyy 
None / 
Fatal / 
 
 
Placebo 
 
 
Treatment medication:  
Unknown / 
 
 
 
 
 
Xxxxxxxx / 
Not recovered/not resolved / 
 
 
 
 
 
Non-drug therapy / 
Recovering/resolving / 
 
 
 
 
 
Other: Xxxxxxxxx 
Recovered/resolved / 
 
 
 
 
 
 
Recovered/resolved with 
 
 
 
 
 
 
sequelae: Xxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
Programmers Notes: 
- Source: A participant reported as having an AE with an action taken of “drug withdrawn” per the AE CRF 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
Severity grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death  
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.7.5 
Treatment Emergent Adverse Events Leading to Premature Trial Discontinuation 
Safety Population 
 
 
Page 99 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
Start Date 
End Date 
Study Day of 
Duration of 
Related  
Severity 
SAE? 
  Participant ID 
Preferred Term / 
 
 
Start of AE 
AE (Days) 
to IP 
Grade 
 
 
AE Term (Verbatim) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
   XXXXXXXX 
 
ddMMMyyyy 
ddMMMyyyy / 
XXX 
XX / 
Yes / 
1 / 
Yes / 
 
 
 
Ongoing 
 
> XX 
No 
2 / 
No 
 
 
 
 
 
 
 
3 / 
 
 
 
 
 
 
 
 
4 / 
 
 
 
 
 
 
 
 
5  
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- Source: A participant reported as having a Trial Completion status of “Participant discontinued from the trial early” and a reason of “Adverse 
event/intercurrent illness” per the TC CRF 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
Severity grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death  
System organ class and preferred term were coded using MedDRA (Version 19.0). 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.7.5 
Treatment Emergent Adverse Events Leading to Premature Trial Discontinuation 
Safety Population 
 
 
Page 100 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
IPM 027 
Action Taken 
Date IP 
Other Action Taken 
Outcome 
  Participant ID 
Preferred Term / 
Treatment 
with IP 
Withdrawn  
 
 
 
AE Term (Verbatim) 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
 
Dapivirine / 
Dose not changed / 
ddMMMyyyy 
None / 
Fatal / 
 
 
Placebo 
Drug interrupted / 
 
Treatment medication:  
Unknown / 
 
 
 
Drug withdrawn / 
 
Xxxxxxx / 
Not recovered/not resolved / 
 
 
 
Not applicable 
 
Non-drug therapy / 
Recovering/resolving / 
 
 
 
 
 
Other: Xxxxxxxxx 
Recovered/resolved / 
 
 
 
 
 
 
Recovered/resolved with 
 
 
 
 
 
 
sequelae: Xxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
Programmers Notes: 
- Source: A participant reported as having a Trial Completion status of “Participant discontinued from the trial early” and a reason of “Adverse event/intercurrent illness” per 
the TC CRF 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
AE= Adverse event; IP = Investigational product; SAE = Serious adverse event 
Severity grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death  
System organ class and preferred term were coded using MedDRA (Version 19.0). 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.7.6 
Serious Treatment Emergent Adverse Events 
Safety Population 
 
 
Page 101 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
Start Date 
End Date 
Study Day  
Duration  Related  
Severity 
Criteria for  
IPM 027 
  Participant ID 
Preferred Term / 
 
 
of Start  
of AE  
to IP 
Grade 
Seriousness 
Treatment 
 
AE Term (Verbatim) 
 
 
of AE 
(Days) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
   XXXXXXXX 
 
ddMMMyyyy 
ddMMMyyyy / 
XXX 
XX / 
Yes / 
1 / 
Death / 
Dapivirine / 
 
 
 
Ongoing 
 
> XX 
No 
2 / 
Life-threatening / 
Placebo 
 
 
 
 
 
 
 
3 / 
Hospitalization/prolong
ed  
 
 
 
 
 
 
 
 
4 / 
hospitalization / 
 
 
 
 
 
 
 
 
5 
Significant  
 
 
 
 
 
 
 
 
 
disability/incapacity / 
 
 
 
 
 
 
 
 
 
Congenital 
anomaly/birth  
 
 
 
 
 
 
 
 
 
defect / 
 
 
 
 
 
 
 
 
 
Medically significant:  
 
 
 
 
 
 
 
 
 
Xxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- List all Criteria for Seriousness, separated with a ; 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Duration of ring removal = Date re-introduced – Date withdrawn+1  
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
Severity grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death 
System organ class and preferred term were coded using MedDRA (Version 19.0). 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.7.6 
Serious Treatment Emergent Adverse Events 
Safety Population 
 
 
Page 102 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
Action Taken with  
Date IP 
Duration of  
Other Action 
Outcome 
  Participant ID 
Preferred Term / 
IP 
Withdrawn 
Ring Removal  
Taken 
 
 
AE Term (Verbatim) 
 
 
(Days) 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
  XXXXXXXX 
 
Dose not changed / 
ddMMMyyyy 
XX 
None / 
Fatal / 
 
 
Drug interrupted / 
 
 
Treatment medication: 
Not recovered/ not resolved / 
 
 
Drug withdrawn / 
 
 
Xxxxxxx / 
Unknown / 
 
 
Not applicable 
 
 
Non-drug therapy / 
Recovering/ resolving / 
 
 
 
 
 
Other: Xxxxxxxxx 
Recovered/ resolved / 
 
 
 
 
 
 
Recovered/ resolved with 
 
 
 
 
 
 
sequelae: Xxxxxxxxxxxxxx 
 
 
 
 
 
 
 
Programmers Notes: 
- List all Criteria for Seriousness, separated with a ; 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Duration of ring removal = Date re-introduced – Date withdrawn+1  
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
Severity grade: 1 = Mild; 2 = Moderate; 3 = Severe; 4 = Potentially life-threatening; 5 = Death 
System organ class and preferred term were coded using MedDRA (Version 19.0). 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.7.7 
Grade 3 or 4 Treatment Emergent Adverse Events 
Safety Population 
 
 
Page 103 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
Start Date 
End Date 
Study Day of 
Duration of 
Related to 
Severity 
SAE? 
IPM 027 
  Participant ID 
Preferred Term / 
 
 
Start of AE 
AE (Days) 
IP 
Grade 
 
Treatment 
 
AE Term (Verbatim) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
  XXXXXXXX 
 
ddMMMyyyy 
ddMMMyyyy / 
XXX 
XX / 
Yes / 
3 / 
Yes / 
Dapivirine / 
 
 
 
Ongoing 
 
> XX 
No 
4 / 
No 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Duration of ring removal = Date re-introduced – Date withdrawn+1  
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
Severity grade: 3 = Severe; 4 = Potentially life-threatening 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


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IPM 032 
 
 
 
 Listing 16.2.7.7 
Grade 3 or 4 Treatment Emergent Adverse Events 
Safety Population 
 
 
Page 104 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
Action Taken with  
Date IP 
Duration of  
Other Action 
Outcome 
  Participant ID 
Preferred Term / 
IP 
Withdrawn 
Ring Removal  
Taken 
 
 
AE Term (Verbatim) 
 
 
(Days) 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
  XXXXXXXX 
 
Dose not changed / 
ddMMMyyyy 
XX 
None / 
Fatal / 
 
 
Drug interrupted / 
 
 
Treatment medication: 
Not recovered/ not resolved / 
 
 
Drug withdrawn / 
 
 
Xxxxxxx / 
Unknown / 
 
 
Not applicable 
 
 
Non-drug therapy / 
Recovering/ resolving / 
 
 
 
 
 
Other: Xxxxxxxxx 
Recovered/ resolved / 
 
 
 
 
 
 
Recovered/ resolved with 
 
 
 
 
 
 
sequelae: Xxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Duration of ring removal = Date re-introduced – Date withdrawn+1  
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
Severity grade: 3 = Severe; 4 = Potentially life-threatening 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.7.8 
Treatment Emergent Adverse Events Leading to Death 
Safety Population 
 
 
Page 105 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
Start Date 
End Date 
Study Day of 
Duration of 
Worsening of  
Related  
SAE? 
  Participant ID 
Preferred Term / 
 
 
Start of AE 
AE (Days) 
Pre-existing 
to IP 
 
 
AE Term (Verbatim) 
 
 
 
 
Condition 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
   XXXXXXXX 
 
ddMMMyyyy 
ddMMMyyyy / 
XXX 
XX / 
Yes / 
Yes / 
Yes / 
 
 
 
Ongoing 
 
> XX 
No 
No 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial 
end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Duration of ring removal = Date re-introduced – Date withdrawn+1  
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.7.8 
Treatment Emergent Adverse Events Leading to Death 
Safety Population 
 
 
Page 106 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
IPM 027 
Action Taken 
Date IP 
Other Action Taken 
  Participant ID 
Preferred Term / 
Treatment 
with IP 
Withdrawn  
 
 
AE Term (Verbatim) 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
 
Dapivirine / 
Dose not changed / 
ddMMMyyyy 
None / 
 
 
Placebo 
Drug interrupted / 
 
Treatment medication: Xxxxxxx / 
 
 
 
Drug withdrawn / 
 
Non-drug therapy / 
 
 
 
Not applicable 
 
Other: Xxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes:  
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.7.9 
Urogenital Treatment Emergent Adverse Events 
Safety Population 
 
 
Page 107 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
Start Date 
End Date 
Study Day of 
Duration of 
Related to 
Severity 
SAE? 
IPM 027 
  Participant ID 
Preferred Term / 
 
 
Start of AE 
AE (Days) 
IP 
Grade 
 
Treatment 
 
AE Term (Verbatim) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
  XXXXXXXX 
 
ddMMMyyyy 
ddMMMyyyy / 
XXX 
XX / 
Yes / 
3 / 
Yes / 
Dapivirine / 
 
 
 
Ongoing 
 
> XX 
No 
4 / 
No 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Duration of ring removal = Date re-introduced – Date withdrawn+1  
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
Severity grade: 3 = Severe; 4 = Potentially life-threatening 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 
 
 
 
 
 
 


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IPM 032 
 
 
 
 Listing 16.2.7.9 
Urogenital Treatment Emergent Adverse Events 
Safety Population 
 
 
Page 108 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
Action Taken with  
Date IP 
Duration of  
Other Action 
Outcome 
  Participant ID 
Preferred Term / 
IP 
Withdrawn 
Ring Removal  
Taken 
 
 
AE Term (Verbatim) 
 
 
(Days) 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
  XXXXXXXX 
 
Dose not changed / 
ddMMMyyyy 
XX 
None / 
Fatal / 
 
 
Drug interrupted / 
 
 
Treatment medication: 
Not recovered/ not resolved / 
 
 
Drug withdrawn / 
 
 
Xxxxxxx / 
Unknown / 
 
 
Not applicable 
 
 
Non-drug therapy / 
Recovering/ resolving / 
 
 
 
 
 
Other: Xxxxxxxxx 
Recovered/ resolved / 
 
 
 
 
 
 
Recovered/ resolved with 
 
 
 
 
 
 
sequelae: Xxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Duration of ring removal = Date re-introduced – Date withdrawn+1  
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
Severity grade: 3 = Severe; 4 = Potentially life-threatening 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 
 
 
 
 


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IPM 032 
 
 
 
Listing 16.2.7.10 
Social Harms Reported as Treatment Emergent Adverse Events 
Safety Population 
 
 
Page 109 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
Start Date 
End Date 
Study Day of 
Duration of 
Related to 
Severity 
SAE? 
IPM 027 
  Participant ID 
Preferred Term / 
 
 
Start of AE 
AE (Days) 
IP 
Grade 
 
Treatment 
 
AE Term (Verbatim) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
  XXXXXXXX 
 
ddMMMyyyy 
ddMMMyyyy / 
XXX 
XX / 
Yes / 
3 / 
Yes / 
Dapivirine / 
 
 
 
Ongoing 
 
> XX 
No 
4 / 
No 
Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Duration of ring removal = Date re-introduced – Date withdrawn+1  
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
Severity grade: 3 = Severe; 4 = Potentially life-threatening 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.7.10 
Social Harms Reported as Treatment Emergent Adverse Events 
Safety Population 
 
 
Page 110 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
System Organ Class / 
Action Taken with  
Date IP 
Duration of  
Other Action 
Outcome 
Related to  
  Participant ID 
Preferred Term / 
IP 
Withdrawn 
Ring Removal  
Taken 
 
Trial 
 
AE Term (Verbatim) 
 
 
(Days) 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
  XXXXXXXX 
 
Dose not changed / 
ddMMMyyyy 
XX 
None / 
Fatal / 
Yes / 
 
 
Drug interrupted / 
 
 
Treatment medication: 
Not recovered/ 
not resolved / 
No 
 
 
Drug withdrawn / 
 
 
Xxxxxxx / 
Unknown / 
 
 
 
Not applicable 
 
 
Non-drug therapy / 
Recovering/ 
resolving / 
 
 
 
 
 
 
Other: Xxxxxxxxx 
Recovered/ 
resolved / 
 
 
 
 
 
 
 
Recovered/ 
resolved with 
 
 
 
 
 
 
 
sequelae: 
Xxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1; else if AESTDTC is known and AE is ongoing at trial end  
then DURATION = “> (Trial Termination Date – AESTDTC+1)” 
- Duration of ring removal = Date re-introduced – Date withdrawn+1  
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
 
AE = Adverse event; IP = Investigational product; SAE = Serious adverse event 
Severity grade: 3 = Severe; 4 = Potentially life-threatening 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


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IPM 032 
 
 
 
Listing 16.2.7.11 
Congenital Anomalies or Birth Defects 
Safety Population 
 
 
Page 111 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Participant 
System Organ Class / 
Start Date 
End Date 
Duration of 
Worsening of  
IPM 027 
Other Action Taken 
ID 
Preferred Term / 
 
 
AE (Days) 
Pre-existing 
Treatment 
 
 
AE  Term (Verbatim) 
 
 
 
Condition 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
 
ddMMMyyyy 
ddMMMyyyy  
XX  
Yes / 
Dapivirine / 
None / 
 
 
 
 
 
No 
Placebo 
Treatment medication: Xxxxxxx / 
 
 
 
 
 
 
 
Non-drug therapy / 
 
 
 
 
 
 
 
Other: Xxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1  
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
 
AE = Adverse event 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.7.1 
Non-Treatment Emergent Adverse Events 
Safety Population 
 
 
Page 112 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Participant 
System Organ Class / 
Start Date 
End Date 
Duration of 
Worsening of  
IPM 027 
Other Action Taken 
ID 
Preferred Term / 
 
 
AE (Days) 
Pre-existing 
Treatment 
 
 
AE  Term (Verbatim) 
 
 
 
Condition 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
 
ddMMMyyyy 
ddMMMyyyy  
XX  
Yes / 
Dapivirine / 
None / 
 
 
 
 
 
No 
Placebo 
Treatment medication: Xxxxxxx / 
 
 
 
 
 
 
 
Non-drug therapy / 
 
 
 
 
 
 
 
Other: Xxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes: 
- If AESTDTC and AEENDTC are both known then DURATION = AEENDTC – AESTDTC +1  
- Concatenate SOC, PT and AE Term separated by ‘/’ 
 
 
 
 
 
 
 
 
AE = Adverse event 
System organ class and preferred term were coded using MedDRA (Version 19.0) 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


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IPM 032 
 
 
 
 Listing 16.2.8.1 
Haematology Results 
Safety Population 
 
 
Page 113 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
 
 
Reference Range 
 
 
 
Centre 
Visit 
Collection 
Parameter (Unit) 
Result 
Lower  
Upper  Indicator 
DAIDS 
Clinically 
Clinical 
  Participant ID 
 
Date 
 
 
Limit 
Limit 
 
Grade 
Significant 
Assessment 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
 
   XXXXXXXX 
Screening / 
ddMMMyyyy 
Erythrocytes (x1012/L) / 
XX.XX / 
XX 
XX 
High / 
1 / 
Yes / 
 
 
Trial Month XX / 
 
Haemoglobin (g/dL) / 
Not done 
 
 
Low / 
2 / 
No 
 
 
Trial Month XX  
 
Haematocrit (L/L) / 
 
 
 
Normal 
3 / 
 
 
 
(Unschedulead X) / 
 
Haematocrit (%) / 
 
 
 
 
4 / 
 
 
 
Exit visit 
 
Platelets (x109 /L) / 
 
 
 
 
N/A 
 
 
 
 
 
Leukocytes (x109 /L) / 
 
 
 
 
 
 
 
 
 
 
Neutrophils (abs.) (x109 /L) / 
 
 
 
 
 
 
 
 
 
 
Lymphocytes (abs.) (x109 /L) / 
 
 
 
 
 
 
 
 
 
 
Monocytes (abs.) (x109 /L) / 
 
 
 
 
 
 
 
 
 
 
Eosinophils (abs.) (x109 /L) / 
 
 
  
 
 
 
 
 
 
 
Basophils (abs.) (x109 /L) / 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


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IPM 032 
 
 
 
 Listing 16.2.8.1 
Haematology Results 
Safety Population 
 
 
Page 114 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Collection 
Parameter (Unit) 
Any  
Description 
IPM 027 
Comments 
  Participant ID 
 
Date 
 
Findings 
of AE 
Treatment 
 
 
 
 
 
AEs? 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
Screening / 
ddMMMyyyy 
Erythrocytes (x1012/L) / 
Yes / 
 
Dapivirine / 
 
 
Trial Month XX / 
 
Haemoglobin (g/dL) / 
No / 
 
Placebo 
 
 
Trial Month XX  
 
Haematocrit (L/L) / 
N/A 
 
 
 
 
(Unscheduled X) / 
 
Haematocrit (%) / 
 
 
 
 
 
Exit visit 
 
Platelets (x109 /L) / 
 
 
 
 
 
 
 
Leukocytes (x109 /L) / 
 
 
 
 
 
 
 
Neutrophils (abs.) (x109 /L) / 
 
 
 
 
 
 
 
Lymphocytes (abs.) (x109 /L) / 
 
 
 
 
 
 
 
Monocytes (abs.) (x109 /L) / 
 
 
 
 
 
 
 
Eosinophils (abs.) (x109 /L) / 
 
 
 
 
 
 
 
Basophils (abs.) (x109 /L)  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.8.2 
Biochemistry Results 
Safety Population 
 
 
Page 115 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
 
 
Reference Range 
DAIDS 
Clinically 
Clinical 
Centre 
Visit 
Collection 
Parameter (Unit) 
Result 
Lower  
Upper  Indicator 
Grade 
Significant 
Assessment 
  Participant ID 
 
Date 
 
 
Limit 
Limit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
 
   XXXXXXXX 
Screening / 
ddMMMyyyy 
Creatinine (µmol/L) / 
XX.XX / 
XX 
XX 
High / 
1 / 
Yes / 
 
 
Trial Month XX / 
 
ALT (IU/L) / 
Not done 
 
 
Low / 
2 / 
No 
 
 
Trial Month XX  
 
AST (IU/L) / 
 
 
 
Normal 
3 / 
 
 
 
(Unscheduled X) / 
 
Sodium (mmol/L) / 
 
 
 
 
4 / 
 
 
 
Exit visit 
 
Potassium (mmol/L) / 
 
 
 
 
N/A 
 
 
 
 
 
Chloride (mmol/L) / 
 
 
 
 
 
 
 
 
 
 
Urea (mmol/L) / 
 
 
 
 
 
 
 
 
 
 
Bilirubin (total) (µmol/L) / 
 
 
 
 
 
 
 
 
 
 
Alkaline phosphatase 
(IUL/L) / 
 
 
 
 
 
 
 
 
 
 
Calcium (mmol/L) / 
 
 
 
 
 
 
 
 
 
 
Phosphate (mmol/L) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; ALT = Alanine aminotransferase; AST = Aspartate aminotransferase 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.8.2 
Biochemistry Results 
Safety Population 
 
 
Page 116 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Visit 
Collection 
Parameter (Unit) 
Any  
Description 
IPM 027 
Comments 
  Participant ID 
 
Date 
 
Findings 
of AE 
Treatment 
 
 
 
 
 
AEs? 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
Screening / 
ddMMMyyyy 
Creatinine (µmol/L) / 
Yes / 
 
Dapivirine / 
 
 
Trial Month XX / 
 
ALT (IU/L) / 
No / 
 
Placebo 
 
 
Trial Month XX  
 
AST (IU/L) / 
N/A 
 
 
 
 
(Unscheduled X) / 
 
Sodium (mmol/L) / 
 
 
 
 
 
Exit visit 
 
Potassium (mmol/L) / 
 
 
 
 
 
 
 
Chloride (mmol/L) / 
 
 
 
 
 
 
 
Urea (mmol/L) / 
 
 
 
 
 
 
 
Bilirubin (total) (µmol/L) / 
 
 
 
 
 
 
 
Alkaline phosphatase (IUL/L) / 
 
 
 
 
 
 
 
Calcium (mmol/L) / 
 
 
 
 
 
 
 
Phosphate (mmol/L) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; ALT = Alanine aminotransferase; AST = Aspartate aminotransferase 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


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IPM 032 
 
 
 
 Listing 16.2.8.3 
Urinalysis and Microscopy Results 
Safety Population 
 
 
Page 117 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Collection 
Visit 
Test Done / 
Category 
Parameter 
Result 
DAIDS 
Clinically 
Other Clinically 
  Participant ID 
Date 
 
Clinically 
 
 
 
Grade 
Significant 
Significant Findings 
 
 
 
Indicated 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Urinalysis / 
 
 
1 / 
Yes / 
No / 
 
 
Trial Month XX / 
No 
Microscopy 
 
 
2 / 
No 
Yes: Xxxxxxxxxxxxxxx 
 
 
Trial Month XX  
 
 
 
 
3 / 
 
 
 
 
(Unscheduled X) / 
 
 
 
 
4 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.8.3 
Urinalysis and Microscopy Results 
Safety Population 
 
 
Page 118 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Collection 
Visit 
Test Done / 
Category 
Parameter 
Clinical  
Any  
Description of 
IPM 027 
  Participant ID 
Date 
 
Clinically 
 
 
Assessment 
Findings 
AE 
Treatment 
 
 
 
Indicated 
 
 
 
AEs? 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Urinalysis / 
 
 
Yes / 
 
Dapivirine / 
 
 
Trial Month XX / 
No 
Microscopy 
 
 
No / 
 
Placebo 
 
 
Trial Month XX  
 
 
 
 
N/A 
 
 
 
 
(Unscheduled X) / 
 
 
 
 
 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
 Listing 16.2.8.4 
Abnormal Clinical Laboratory Data 
Safety Population 
 
 
Page 119 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Date of  
Visit 
Parameter 
Sample 
Result 
Abnormal Result 
Clinically 
Any  
IPM 027 
  Participant ID 
Exam 
 
 
Type 
 
Specifics 
Significant 
Findings 
Treatment 
 
 
 
 
 
 
 
 
AEs? 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
 
 
Not examined / 
 
Yes /  
Yes / 
Dapivirine / 
 
 
Trial Month XX / 
 
 
Normal / 
 
No 
No / 
Placebo 
 
 
Trial Month XX  
 
 
Abnormal / 
 
 
N/A  
 
 
 
(Unscheduled X) / 
 
 
Not Applicable 
 
 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: If a subject presents with an abnormal result, include all other relevant test for the subject (i.e. show all results 
for all visits) 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
 Listing 16.2.8.5 
Vital Signs 
Safety Population 
 
 
Page 120 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Date of  
Visit 
Weight 
Temperature 
Pulse 
Respiration Rate 
Blood Pressure 
  Participant ID 
Exam 
 
(kg) 
(oC) 
(beats/min) 
(breaths/min) 
(mmHg) 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
XXX / 
XX.X / 
XXX / 
XX / 
XXX/XXX / 
 
 
Trial Month XX / 
Not done 
Not done 
Not done 
Not done 
Not done 
 
 
Trial Month XX  
 
 
 
 
 
 
 
(Unscheduled X) / 
 
 
 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
 Listing 16.2.8.6 
Physical Examination 
Safety Population 
 
 
Page 121 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Date of  
Visit 
Body System 
Result 
Abnormal Result 
Clinically 
Any Findings 
  Participant ID 
Exam 
 
or Part 
 
Specifics 
Significant 
AEs? 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
General 
Not examined / 
 
Yes /  
Yes / 
 
 
Trial Month XX / 
appearance / 
Normal / 
 
No 
No / 
 
 
Trial Month XX  
Gastrointestinal/ Abdomen / 
Abnormal / 
 
 
N/A  
 
 
(Unscheduled X) / 
Neck / 
Not Applicable 
 
 
 
 
 
Exit visit 
Lymph node / 
 
 
 
 
 
 
 
Cardiovascular/ Heart / 
 
 
 
 
 
 
 
Respiratory/Lungs / 
 
 
 
 
 
 
 
Neurological / 
 
 
 
 
 
 
 
Skin / 
 
 
 
 
 
 
 
Eyes / 
 
 
 
 
 
 
 
Ears, nose, throat / 
 
 
 
 
 
 
 
Other: Xxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; CRF = Case report form 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.8.6 
Physical Examination 
Safety Population 
 
 
Page 122 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Date of  
Visit 
Body System 
Description of 
IPM 027 
Comments 
  Participant ID 
Exam 
 
or Part 
AE 
Treatment 
 
 
 
 
 
 
 
 
Centre XXX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
General 
 
Dapivirine / 
 
 
 
Trial Month XX / 
appearance / 
 
Placebo 
 
 
 
Trial Month XX  
Gastrointestinal/ Abdomen / 
 
 
 
 
 
(Unscheduled X) / 
Neck 
 
 
 
 
 
Exit visit 
Lymph node / 
 
 
 
 
 
 
Cardiovascular/ Heart / 
 
 
 
 
 
 
Respiratory/Lungs / 
 
 
 
 
 
 
Neurological / 
 
 
 
 
 
 
Skin / 
 
 
 
 
 
 
Eyes / 
 
 
 
 
 
 
Ears, nose, throat / 
 
 
 
 
 
 
Other: Xxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; CRF = Case report form 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
 Listing 16.2.8.7 
Menses Information and Pregnancy Test Results 
Safety Population 
 
 
Page 123 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
Menses Information 
 
Pregnancy Test 
Centre 
Collection 
Visit 
N/A at Scheduled 
First Day of Last 
Changes to Menses  
 
Urine Test  
Serum Collection 
Serum Test 
  Participant ID 
Date 
 
Visits 
Menstrual Period 
from Previous Visit 
 
Result 
Date 
Result 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes  
ddMMMyyyy / 
No / 
 
Negative / 
ddMMMyyyy / 
Negative / 
 
 
Trial Month XX / 
 
N/A 
N/A / 
 
Positive / 
N/A 
Equivocal / 
 
 
Trial Month XX  
 
 
Yes: Xxxxxxxxxxxx 
 
Not done 
 
positive 
 
 
(Unscheduled X) / 
 
 
 
 
 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Capture all methods used to estimate date of deliver, separated by ‘;’ 
 
 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.8.7 
Menses Information and Pregnancy Test Results 
Safety Population 
 
 
Page 124 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
 
 
Pregnancy Report 
Centre 
Collection 
Visit 
On Contraceptive at Positive 
 
Estimated Day of Delivery 
Information Used to Estimate 
  Participant ID 
Date 
 
Pregnancy Test: Name 
 
 
Date of Delivery 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes: Xxxxxxxxxxxx / 
 
ddMMMyyyy / 
Last menstrual period / 
 
 
Trial Month XX / 
No 
 
N/A 
Initial ultrasound <20 w / 
 
 
Trial Month XX  
 
 
 
Initial ultrasound ≥ 20 w / 
 
 
(Unscheduled X) / 
 
 
 
Physical exam / 
 
 
Exit visit 
 
 
 
Other: Xxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
Programmers Note: Capture all methods used to estimate date of deliver, separated by ‘;’ 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.8.7 
Menses Information and Pregnancy Test Results 
Safety Population 
 
 
Page 125 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
Pregnancy Report 
 
Pregnancy Outcome 
Centre 
Collection 
Visit 
History of Pregnancy Complications 
 
No. of Pregnancy 
Outcome Date 
Delivery / Outcome 
  Participant ID 
Date 
 
or Fetal/Infant Congenital Anomalies 
 
Outcomes Resulted 
 
Place 
 
 
 
 
 
From Report 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
No / 
 
X 
ddMMMyyyy 
Home / 
 
 
Trial Month XX / 
Yes: Xxxxxxxxxxxxxxxxxxx 
 
 
 
Hospital / 
  
 
Trial Month XX  
 
 
 
 
Clinic / 
 
 
(Unscheduled X) / 
 
 
 
 
Unkown / 
 
 
Exit visit 
 
 
 
 
Other: Xxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Capture all methods used to estimate date of deliver, separated by ‘;’ 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.8.7 
Menses Information and Pregnancy Test Results 
Safety Population 
 
 
Page 126 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
Pregnancy Outcome 
Centre 
Collection 
Visit 
Outcome 
Delivery-Related Complications 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Full term live birth (≥37 weeks): C-section / 
None / 
 
 
Trial Month XX / 
Full term live birth (≥37 weeks): Standard vaginal / 
Intrapartum hemorrhage / 
 
 
Trial Month XX  
Full term live birth (≥37 weeks): Operative vaginal / 
Postpartum hemorrhage / 
 
 
(Unscheduled X) / 
Premature term live birth (< 37 weeks): C-section / 
Non-reassuring fetal status / 
 
 
Exit visit 
Premature term live birth (< 37 weeks): Standard vaginal / 
Chorioamnionitis / 
 
 
 
Premature term live birth (< 37 weeks): Operative vaginal / 
Other: Xxxxxxxxxxxxx 
 
 
 
Stillbirth/intrauterine fetal demise (≥20 weeks) / 
 
 
 
 
Spontaneous abortion (< 20 weeks) / 
 
 
 
 
Ectopic pregnancy / 
 
 
 
 
Therapeutic abortion / 
 
 
 
 
Non-therapeutic abortion / 
 
 
 
 
Ongoing at trial end / 
 
 
 
 
Other: Xxxxxxxxxxxxxxxxxxxxx / 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Capture all methods used to estimate date of deliver, separated by ‘;’ 
 
 
 
 
 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.8.7 
Menses Information and Pregnancy Test Results 
Safety Population 
 
 
Page 127 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
Pregnancy Outcome 
Centre 
Collection 
Visit 
Non-Delivery-related 
Congenital Anomalies 
  Participant ID 
Date 
 
Complications 
Indicator 
 
 
 
 
 
Centre XX 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
None / 
 
 
 
Trial Month XX / 
Hypertensive disorders 
 
 
 
Trial Month XX  
of pregnancy / 
 
 
 
(Unscheduled X) / 
Gestational diabetes / 
 
 
 
Exit visit 
Other: Xxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Capture all methods used to estimate date of deliver, separated by ‘;’ 
 
 
 
 
 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
 Listing 16.2.8.8 
Sexually Transmitted Infections  
Safety Population 
 
 
Page 128 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Collection 
Visit 
Parameter 
Result 
Blood Present at  
Any Findings 
AE Description 
  Participant ID 
Date 
 
 
 
Collection of Cervico- 
AEs? 
 
 
 
 
 
 
vaginal Samples 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Trichomonas rapid test / 
 
Yes / 
Yes / 
 
 
 
Trial Month XX / 
Gonorrhea / 
 
No 
No / 
 
 
 
Trial Month XX  
Chlamydia / 
 
 
N/A 
 
 
 
(Unscheduled X) / 
Syphilis RPR screening test / 
 
 
 
 
 
 
Exit visit 
Syphilis RPR titre / 
 
 
 
 
 
 
 
Syphilis confirmatory test TPHA/TPPA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; RPR = Rapid plasma reagin; TPHA = Treponema pallidum haemagglutination test; TPPA = Treponema pallidum particle agglutination assay 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.8.8 
Sexually Transmitted Infections  
Safety Population 
 
 
Page 129 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Collection 
Visit 
Parameter 
Comments 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Trichomonas rapid test / 
 
 
 
Trial Month XX / 
Gonorrhea / 
 
 
 
Trial Month XX  
Chlamydia / 
 
 
 
(Unscheduled X) / 
Syphilis RPR screening test / 
 
 
 
Exit visit 
Syphilis RPR titre / 
 
 
 
 
Syphilis confirmatory test TPHA/TPPA 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; RPR = Rapid plasma reagin; TPHA = Treponema pallidum haemagglutination test; TPPA = Treponema pallidum particle agglutination assay 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
 Listing 16.2.8.9 
HIV-1 Seroconversion 
m-ITT Population 
 
 
Page 130 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Collection  
Visit 
Seroconversion 
Category 
Parameter 
Result 
  IPM 027 Treatment 
Date 
 
Timepoint 
 
 
 
    Participant ID 
 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
  Dapivirine/ Placebo 
 
 
 
 
 
 
    XXXXXXXX 
ddMMMyyyy 
Screening / 
On IP / 
HIV Rapid test / 
Test 1: Determine / 
Reactive / 
 
 
Trial Month XX / 
Prior to IP / 
Seroconversion / 
Test 1: Xxxxxxxxxx / 
Non-reactive / 
 
 
Trial Month XX  
After IP 
Seroconversion 
Test 2: OraQuick / 
Negative / 
 
 
(Unscheduled X) / 
 
additional testing / 
Test 2: Xxxxxxx / 
Positive / 
 
 
Exit visit 
 
HIV RNA PCR / 
Test 3: UniGold / 
Indeterminate / 
 
 
 
 
HIV seroconversion 
Test 3: Xxxxxxx / 
< 40 cop/mL / 
 
 
 
 
evaluation / 
HIV-1 Western Blot / 
>= 40 cop/mL: XXXX / 
 
 
 
 
 
Repeat HIV-1 Western Blot / 
Xxxxxxxx / 
 
 
 
 
 
HIV-2 Western Blot / 
Yes / 
 
 
 
 
 
Reapeat HIV-2 Western Blot / 
No / 
 
 
 
 
 
RNA PCR Testing: Confirmed  
N/A / 
 
 
 
 
 
seroconversion / 
Not done 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; HIV-1 = Human immunodeficiency virus type 1; IP = Investigational product; IRE = Immediately reportable event; PCR = Polymerase chain reaction; 
RNA = Ribonucleic acid 
a Based on Retrospective HIV RNA PCR results 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
 Listing 16.2.8.9 
HIV-1 Seroconversion 
m-ITT Population 
 
 
Page 131 of 154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Collection  
Visit 
HIV 
Genotype Sample Taken / 
Reported  
Contraceptive When 
Estimated Point 
  IPM 027 Treatment 
Date 
 
Subtype 
Analysed / Successful 
as IREb 
Seroconverted: 
of Infection  
    Participant ID 
 
 
 
Assessment 
 
Method and Name 
On IP?a 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
  Dapivirine/ Placebo 
 
 
 
 
 
 
 
    XXXXXXXX 
ddMMMyyyy 
Screening / 
 
Yes/Yes/Yes / 
Yes / 
Oral: Xxxxxxxxx / 
 
 
 
Trial Month XX / 
 
Yes/Yes/No / 
No 
Transdermal patch / 
 
 
 
Trial Month XX  
 
Yes/No/No 
 
Long acting injectable 
 
 
 
(Unscheduled X) / 
 
No 
 
Condoms /progestins / 
 
 
 
Exit visit 
 
 
 
Subcutaneous implant / 
 
 
 
 
 
 
 
IUD / 
 
 
 
 
 
 
 
Surgical sterilization / 
 
 
 
 
 
 
 
Other: Xxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; HIV-1 = Human immunodeficiency virus type 1; IP = Investigational product; IRE = Immediately reportable event; PCR = Polymerase chain reaction; 
RNA = Ribonucleic acid 
a Based on Retrospective HIV RNA PCR results 
b A positive/reactive HIV rapid test result is reported as an IRE 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM); 
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


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IPM 032 
 
 
 
 Listing 16.2.8.9 
HIV-1 Seroconversion 
m-ITT Population 
 
 
Page 132 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Collection  
Visit 
Specifics of Point of Infection 
ARV Treatment 
Comments 
  IPM 027 Treatment 
Date 
 
 
Initiated 
 
    Participant ID 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
  Dapivirine/ Placebo 
 
 
 
 
 
    XXXXXXXX 
ddMMMyyyy 
Screening / 
HIV RNA copies present 
Yes: Xxxxxx  / 
 
 
 
Trial Month XX / 
at enrollment / 
No  
 
 
 
Trial Month XX  
IP discontinued due to  
 
 
 
 
(Unscheduled X) / 
pregnancy / 
 
 
 
 
Exit visit 
IP removed for an extended  
 
 
 
 
 
period due to AE: Xxxxxxxxx / 
 
 
 
 
 
Ring non-user / 
 
 
 
 
 
Other: Xxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event; HIV-1 = Human immunodeficiency virus type 1; IP = Investigational product; IRE = Immediately reportable event; PCR = Polymerase chain reaction; 
RNA = Ribonucleic acid 
aBased on Retrospective HIV RNA PCR results 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM); 
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.11 
HIV-1 Seroconversion on Investigational Product 
Safety Population 
 
 
Page 133 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
IPM 027 Treatment 
Date of HIV-1  
Date of  
Date of  
Days between 
Time to First 
Residual  
Appearance of  
Colour of Ring 
  Participant ID 
Seroconversion 
Last Neg. 
First HIV-1 
Last Neg. and  
HIV-1 RNA 
Dapivirine in Ring 
Ring At First  
At First HIV-1  
 
 
HIV-1 
Detection 
First HIV-1 
Detection 
(mg) at First HIV-1 
HIV-1 RNA  
RNA Detection 
 
 
RNA Result 
 
RNA Detection 
 
RNA Detection 
Detection 
 
 
 
 
 
 
 
 
 
 
Dapivirine/ Placebo 
 
 
 
 
 
 
 
 
  XXXXXXXX 
ddMMMyyyy 
ddMMMyyyy  
ddMMMyyyy  
XXX 
XXX 
XX.X 
Appears used/ 
Tan /  
 
 
 
 
 
 
 
Appears not 
used 
White to off-white/ 
 
 
 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please list Mutations as a string ordered by position 
 
 
 
 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1; RNA = Ribonucleic acid 
 
 


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IPM 032 
 
 
 
Listing 16.2.8.12 
Participants with Drug Resistance Mutations 
Safety Population 
 
 
Page 134 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
IPM 027 Treatment 
Date of HIV-1  
Seroconversion 
Trial Visit 
Collection  
HIV-1 RNA  
Associated Drug 
Days Since 
Days Since 
  Participant ID 
Seroconversion 
Timepoint 
 
Date 
Results 
Resistance  
HIV-1 Sero- 
HIV-1 RNA 
 
 
 
 
 
(cop/mL) 
Mutations 
conversion 
Detection 
 
 
 
 
 
 
 
 
 
Dapivirine/ Placebo 
 
 
 
 
 
 
 
 
  XXXXXXXX 
ddMMMyyyy 
On IP / 
Trial Month XX 
 
XX / 
NNRTI: Xxxxxxx / 
XXX 
XXX 
 
 
After IP / 
 
 
Not detected 
NTRI: Xxxxxxx / 
 
 
 
 
Prior to IP 
 
 
 
PI Major: Xxxxxx / 
 
 
 
 
 
 
 
 
No mutations 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please list Mutations as a string ordered by position 
 
 
 
 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1; NNRTI = Non-nucleoside reverse transcriptase inhibitor;  NTRI = Nucleoside reverse transcriptase inhibitor; 
RNA = Ribonucleic acid  
The Stanford University HIV-1 Drug Resistance Database version 8.4 (dated 2017-06-16) was used


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.13 
HIV-1 NNRTI Drug Susceptibility: Stanford Interpretation of Genotype 
Safety Population 
 
 
Page 135 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
 
 
 
 
 
 
 
NNRTI Stanford Mutation Score / Classification 
IPM 027 Treatment 
Serocon- 
Sample 
Visit 
Date of 
Days Since 
Date of 
Days Since 
HIV 
NNRTI  
Efa-  
Etra- 
Nevi- 
Rilpi- 
   Participant ID 
version 
Date 
 
HIV-1 
Sero- 
HIV-1 Sero- 
HIV-1 RNA 
HIV-1 RNA 
Subtype 
mutations 
virenz 
virine 
rapine 
virine 
 
Timepoint 
 
 
conversion 
conversion 
Detection 
Detection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dapivirine/ Placebo 
 
 
 
 
 
 
 
 
 
 
 
 
 
  XXXXXXXX 
On IP / 
ddMM
Myyyy 
Trial 
Month 
XX / 
ddMMMyy
yy 
XXX 
ddMMMyyyy 
XXX 
 
XXXX 
XX: 1 / 
XX: 1 / 
XX: 1 / 
XX: 1 / 
 
After IP / 
 
LPUV / 
 
 
 
 
 
 
XX: 2 / 
XX: 2 / 
XX: 2 / 
XX: 2 / 
 
Prior to IP 
 
Exit 
Visit 
 
 
 
 
 
 
XX: 3 / 
XX: 3 / 
XX: 3 / 
XX: 3 / 
 
 
 
 
 
 
 
 
 
 
XX: 4 / 
XX: 4 / 
XX: 4 / 
XX: 4 / 
 
 
 
 
 
 
 
 
 
 
XX: 5 
XX: 5 
XX: 5 
XX: 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please list Mutations as a string ordered by position 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1; LPUV = Last product use visit; NNRTI = Non-nucleoside reverse transcriptase inhibitor;  RNA = Ribonucleic acid  
NNRTI resistance mutation score: 1 = Susceptible (< 10); 2 = Potential low-lebel resistance (10 -< 15); 3 = Low-level resistance (15 - < 30); 4 = Intermediate resistance (30 -< 60); 
5 = High-level resistance (> 60)  
The Stanford University HIV-1 Drug Resistance Database version 8.4 (dated 2017-06-16) was used to  identify mutations associated with any resistance score to NRTI, NRTI or PI


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.14 
Population-Based Sequencing: Mutations per Region 
Safety Population 
HIV-1 Serovonversions 
 
Page 136 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
IPM 027 Treatment 
Date of 
Seroconversion 
Day of 
Days Since 
Date of  
Days Since 
Sample 
Visit Sample 
Visit  
Region 
Mutations 
  Participant ID  
HIV-1 Sero- 
Timepoint 
HIV-1 Sero- 
HIV-1 Sero- 
First HIV-1 
HIV-1 RNA 
Date 
Taken 
Day 
 
 
 
conversion 
 
conversion 
conversion 
RNA Detection 
Detection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Dapivirine/ Placebo 
 
 
 
 
 
 
 
 
 
 
 
  XXXXXXXX 
ddMMMyyyy 
On IP / 
XXX 
XX 
 
XXX 
ddMMMyyyy 
Trial Month 
XX / 
XXX 
RT 
XXXX 
 
 
After IP / 
 
 
 
 
 
LPUV / 
 
PR 
 
 
 
Prior to IP 
 
 
 
 
 
Exit Visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Notes:  
- 
Populate Mutations with RT changes from reference sequence as a string ordered by position 
- 
Please repeat the listing for the following subgroups: HIV-1 Seroconconverted On Treatment; HIV-1 Seroconverted After Treatment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1; LPUV = Last product use visit; RNA = Ribonucleic acid 
The consensus subtype B sequence from the Stanford University HIV-1 database was used as reference 
 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.15 
Population-Based Genotyping Amongst Participants who HIV-1 Seroconverted 
Saftey Population 
 
 
Page 137 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
IPM 027 Treatment 
HIV-1 Sero- 
Date of 
Day of HIV-1 
Date of  
RNA PCR 
Visit Sample 
Genotyping 
Days Since 
  Participant ID 
Conversion 
of HIV-1 Sero- 
Serocon- 
Last Ring 
Sample 
Taken 
Performed? 
HIV-1 
 
Timepoint 
conversion 
version 
Exposure 
Date 
 
 
Seroconversion 
 
 
 
 
 
 
 
 
 
Dapivirine/ Placebo 
 
 
 
 
 
 
 
 
  XXXXXXXX 
Prior to IP/ 
ddMMMyyyy 
XXX 
ddMMMyyyy 
ddMMMyyyy 
Trial Month X / 
Yes / 
 
 
On IP / 
 
 
 
 
LPUV / 
No 
 
 
After IP 
 
 
 
 
Exit Visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1; LPUV = Last product use visit; RNA = Ribonucleic acid  


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.15 
Population-Based Genotyping Amongst Participants who HIV-1 Seroconverted 
Saftey Population 
 
 
Page 138 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
IPM 027 Treatment 
HIV-1 Sero- 
Date of 
Days Since 
Date of First 
Days Since  
Days Since 
HIV RNA PCR 
  Participant ID 
Conversion 
of HIV-1 Sero- 
Study Start 
HIV-1 RNA 
HIV-1 RNA 
Last Ring 
Results (cop/mL) 
 
Timepoint 
conversion 
 
Detection 
Detection 
Exposure 
At Seroconversion 
 
 
 
 
 
 
 
 
Dapivirine/ Placebo 
 
 
 
 
 
 
 
  XXXXXXXX 
Prior to IP/ 
ddMMMyyyy 
XXX 
ddMMMyyyy 
XXX 
XXX 
XXXX 
 
On IP / 
 
 
 
 
 
 
 
After IP 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HIV-1 = Human immunodeficiency virus type 1; LPUV = Last product use visit; RNA = Ribonucleic acid  
 
 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.16 
Pelvic/ Speculum Examinations 
Safety Population 
 
 
Page 139 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
 
 
Vulvar 
Centre 
Date of 
Visit 
Examined 
Abnormal 
Indicator 
Parameter 
Clinically 
Grade 
  Participant ID 
Examination 
 
 
Findings 
 
 
Significant 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Yes / 
Vulvar erythema / 
Ulcer / 
Yes / 
X 
 
 
Trial Month XX / 
No 
No 
Vulvar edema / 
Blister / 
No 
 
 
 
Trial Month XX  
 
 
Vulvar rash / 
Pustule / 
 
 
 
 
(Unscheduled X) / 
 
 
Vulvar tenderness / 
Peeling / 
 
 
 
 
Exit visit 
 
 
Bartholin’s or Skene’s 
Ecchymosis / 
 
 
 
 
 
 
 
gland abnormality / 
Other: Xxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
Not done 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
 
AE = Adverse event 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.16 
Pelvic/ Speculum Examinations 
Safety Population 
 
 
Page 140 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
 
Vaginal 
Centre 
Examination 
Visit 
Examined 
Indicator 
Parameter 
Clinically 
Grade 
  Participant ID 
Date 
 
 
 
 
Significant 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Vaginal erythema / 
Ulcer / 
Yes / 
X 
 
 
Trial Month XX / 
No 
Vaginal edema / 
Blister / 
No 
 
 
 
Trial Month XX  
 
Vaginal masses / 
Pustule / 
 
 
 
 
(Unscheduled X) / 
 
Vaginal abrasions or  
Peeling / 
 
 
 
 
Exit visit 
 
lacerations / 
Ecchymosis / 
 
 
 
 
 
 
Vaginal tenderness / 
Other: Xxxxxxxxxxxxxxx 
 
 
 
 
 
 
Vaginal discharge: Slight / 
 
 
 
 
 
 
 
Vaginal discharge: Mild / 
 
 
 
 
 
 
 
Vaginal discharge: Pooling 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
AE = Adverse event  
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.16 
Pelvic/ Speculum Examinations 
Safety Population 
 
 
Page 141 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
 
Cervical 
Centre 
Examination 
Visit 
Examined 
Indicator 
Parameter 
Clinically 
Grade 
  Participant ID 
Date 
 
 
 
 
Significant 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Cervical erythema / 
Ulcer / 
Yes / 
X 
 
 
Trial Month XX / 
No 
Cervical edema and/or  
Blister / 
No 
 
 
 
Trial Month XX  
 
friability/ 
Pustule / 
 
 
 
 
(Unscheduled X) / 
 
Cervical masses / 
Peeling / 
 
 
 
 
Exit visit 
 
Cervical motion tenderness / 
Ecchymosis / 
 
 
 
 
 
 
Cervical discharge 
Other: Xxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
AE = Adverse event 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.16 
Pelvic/ Speculum Examinations 
Safety Population 
 
 
Page 142 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
 
General / Other 
Centre 
Examination 
Visit 
Examined 
Indicator 
Parameter 
Clinically 
Grade 
  Participant ID 
Date 
 
 
 
 
Significant 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
 
 
Yes / 
X 
 
 
Trial Month XX / 
No 
 
 
No 
 
 
 
Trial Month XX  
 
 
 
 
 
 
 
(Unscheduled X) / 
 
 
 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
AE = Adverse event 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 


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IPM 032 
 
 
 
Listing 16.2.8.16 
Pelvic/ Speculum Examinations 
Safety Population 
 
 
Page 143 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Examination 
Visit 
Examined 
Description 
Cervical 
IPM 027 
Comments 
  Participant ID 
Date 
 
 
of AE 
Ectopy 
Treatment 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Yes / 
Xxxxxxxxxx 
0% / 
Dapivirine / 
 
 
 
Trial Month XX / 
No 
 
1 – 25% / 
Placebo 
 
 
 
Trial Month XX  
 
 
26 – 50% / 
 
 
 
 
(Unscheduled X) / 
 
 
51 – 75% / 
 
 
 
 
Exit visit 
 
 
76 – 100% 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
AE = Adverse event  
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.17 
Cervical Cytology Results 
Safety Population 
 
 
Page 144 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Sample 
Visit 
Pap Test Results: End of Form Date 
Reported as  
Comments 
  Participant ID 
Date 
 
 
AE: Description 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
Not done / 
Yes: Xxxxxxx / 
 
 
 
Trial Month XX / 
Documentation of normal cervical cytology / 
No / 
 
 
 
Trial Month XX  
results within 1 year of Screening: ddMMMyyyy / 
N/A 
 
 
 
(Unscheduled X) / 
Negative for intraepithelial lesion or cancer  
 
 
 
 
Exit visit 
(malignancy) / 
 
 
 
 
 
ASCUS / 
 
 
 
 
 
ASC-H / 
 
 
 
 
 
SIL-low grade (LSIL) / 
 
 
 
 
 
SIL-high grade (HSIL) / 
 
 
 
 
 
AGC / 
 
 
 
 
 
AGC-favor neoplastic / 
 
 
 
 
 
Cancer / 
 
 
 
 
 
Other: Xxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AE = Adverse event 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.18.1 
Social Harms Report 
Safety Population 
 
 
Page 145 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Report 
Visit 
Reported Social Harm (Verbatim) 
Person Responsible 
Similar Event  
Event Due To Your 
  Participant ID 
Date 
 
 
 
Happened Before 
Involvement in Trial 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
 
Sex partner / 
No / 
No / 
 
 
Trial Month XX / 
 
Family member / 
Yes: Xxxxxxxxxxx 
Yes: Xxxxxxxxxxxxxx / 
 
 
Trial Month XX  
 
Friends/neigbours / 
 
Not sure: Xxxxxxxxxxx 
 
 
(Unscheduled X) / 
 
Health worker / 
 
 
 
 
Exit visit 
 
Co-workers / 
 
 
 
 
 
 
Church member / 
 
 
 
 
 
 
Known community members / 
 
 
 
 
 
 
Strangers / 
 
 
 
 
 
 
Other: Xxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
AE = Adverse event; RC = Research centre 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.18.1 
Social Harms Report 
Safety Population 
 
 
Page 146 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Report 
Visit 
Reported Social Harm (Verbatim) 
Resolution Status 
Referral for 
Impact on Quality 
  Participant ID 
Date 
 
 
(Participant Opinion) 
Support 
of Life 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
 
Yes / 
Yes / 
Minor disturbance / 
 
 
Trial Month XX / 
 
No / 
No 
Major disturbance / 
 
 
Trial Month XX  
 
Not sure 
 
Moderate disturbance 
 
 
(Unscheduled X) / 
 
 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
AE = Adverse event; RC = Research centre 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.18.1 
Social Harms Report 
Safety Population 
 
 
Page 147 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
 
Type of Social Harm 
Centre 
Report 
Visit 
Reported Social Harm (Verbatim) 
Physical 
Description of  
Emotional 
  Participant ID 
Date 
 
 
 
Reported AE 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
 
None / 
Xxxxxxxx / 
None / 
 
 
Trial Month XX / 
 
Beating/hitting/slapping / 
No AE 
Yelling/shouting / 
 
 
Trial Month XX  
 
Shoving/tripping / 
 
Shunning/ignoring / 
 
 
(Unscheduled X) / 
 
Cutting/burning/shooting 
 
Gossiping / 
 
 
Exit visit 
 
Witholding basic needs / 
 
Emotional harm to others / 
 
 
 
 
Other: Xxxxxxxxxxx 
 
Physical harm to others / 
 
 
 
 
 
 
Financial harm to others / 
 
 
 
 
 
 
Other: Xxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
Programmers Note: Please capture multiple responses, separated with a ‘;’ 
 
 
 
 
 
 
 
 
AE = Adverse event; RC = Research centre 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.18.1 
Social Harms Report 
Safety Population 
 
 
Page 148 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
 
Type of Social Harm 
 
Action(s) Taken 
Centre 
Report 
Visit 
Reported Social Harm (Verbatim) 
Financial 
 
By Participant 
  Participant ID 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
 
None / 
 
None / 
 
 
Trial Month XX / 
 
Lost source of income / 
 
Sought support services / 
 
 
Trial Month XX  
 
Lost home / 
 
Sought counselling / 
 
 
(Unscheduled X) / 
 
Victim of theft / 
 
Sought medical care / 
 
 
Exit visit 
 
Cost of care for physical/emotional 
harm / 
 
Other: Xxxxxxxxxxxxxxxxx 
 
 
 
 
Loss of resources / 
 
 
 
 
 
 
Other: Xxxxxxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture all responses, separated by ‘;’ 
 
 
 
 
 
 
 
AE = Adverse event; RC = Research centre 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.18.1 
Social Harms Report 
Safety Population 
 
 
Page 149 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
 
Action(s) Taken 
 
Centre 
Report 
Visit 
Reported Social Harm (Verbatim) 
By RC 
Other 
Resolution Status 
  Participant ID 
Date 
 
 
 
 
(RC Opinion)  
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
 
None / 
None / 
Resolved / 
 
 
Trial Month XX / 
 
Referred to support services / 
Xxxxxxxxx 
Unresolved at this visit / 
 
 
Trial Month XX  
 
Referred for counselling / 
 
   
 
 
(Unscheduled X) / 
 
Medical Care / 
 
 
 
 
Exit visit 
 
Other: Xxxxxxxxxxxxxxxxx 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture all responses, separated by ‘;’ 
 
 
 
 
 
 
 
AE = Adverse event; RC = Research centre 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 
 


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.18.1 
Social Harms Report 
Safety Population 
 
 
Page 150 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Date of 
Follow-up 
Reported Social Harm (Verbatim) 
Resolution  
Comments 
  Participant ID 
Report 
Report Visit 
 
Date 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
 
ddMMMyyyy 
 
 
 
Trial Month XX / 
 
 
 
 
 
Trial Month XX  
 
 
 
 
 
(Unscheduled X) / 
 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture all responses, separated by ‘;’ 
 
 
 
 
 
 
AE = Adverse event; RC = Research centre 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.18.2 
Social Harms Follow-up Report 
Safety Population 
 
 
Page 151 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Date of 
Follow-up 
Reported Social Harm (Verbatim) 
Additional Info 
Additional Information  
Resolution Status 
  Participant ID 
Report 
Report Visit 
 
Report Date 
(Verbatim) 
(RC Opinion) 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
 
ddMMMyyyy 
 
Resolved / 
 
 
Trial Month XX / 
 
 
 
Unresolved at the visit / 
 
 
Trial Month XX  
 
 
 
Ongoing at participant's last 
visit:  
 
 
(Unscheduled X) / 
 
 
 
xxxxxxxxxxxxxxxxxxx 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture all responses, separated by ‘;’ 
 
 
 
 
 
 
 
AE = Adverse event; RC = Research centre 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


 LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.18.2 
Social Harms Follow-up Report 
Safety Population 
 
 
Page 152 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
Date of 
Follow-up 
Reported Social Harm (Verbatim) 
Resolution  
Comments 
  Participant ID 
Report 
Report Visit 
 
Date 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
   XXXXXXXX 
ddMMMyyyy 
Screening / 
 
ddMMMyyyy 
 
 
 
Trial Month XX / 
 
 
 
 
 
Trial Month XX  
 
 
 
 
 
(Unscheduled X) / 
 
 
 
 
 
Exit visit 
 
 
 
 
 
 
 
 
 
Programmers Note: Please capture all responses, separated by ‘;’ 
 
 
 
 
 
 
AE = Adverse event; RC = Research centre 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG)


9LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.19 
Timing Profile 
Safety Population 
 
 
Page 153 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
Centre 
IPM 027 
Trial 
Date 
Start Date 
End Date 
Duration 
Directly Enrolled 
    Participant ID 
Treatment 
 
Category 
 
 
(Days) 
In IPM 032? 
 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
 
 
  XXXXXXXX 
Dapivirine / 
IPM 032 / 
Time on IP / 
ddMMMyyyy 
ddMMMyyyy 
XXX 
Yes / 
 
Placebo 
IPM 027 
Time on open-label IP / 
 
 
 
No 
 
 
 
Time off IP / 
 
 
 
 
 
 
 
Total time on IP / 
 
 
 
 
 
 
 
Time off between IPM 027 and IPM 032 / 
 
 
 
 
 
 
 
Time on randomized IP / 
 
 
 
 
 
 
 
IPM 027 exit date / 
 
 
 
 
 
 
 
IPM 032 exit date 
 
 
 
 
 
 
 
Time to seroconversion / 
 
 
 
 
 
 
 
Time to first positive HIV RNA / 
 
 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IP = Investigational product 
Centre 01: Madibeng Centre for Research (MCR); Centre 02: MatCH Research Unit (MRU); Centre 04: Qhakaza Mbokodo (QM);  
Centre 06: MRC/UVRI & LSHTM Uganda Research Unit (MRC/UVRI); Centre 07: Desmond Tutu HIV Foundation (DTHF), Masiphumelele; Centre 08: Ndlovu Care Group (NCG) 
 
 
 
 
 
 
 
 


9LISTING SHELLS                                                                                                                                                                                     
 
 
 
IPM 032 
 
 
 
Listing 16.2.8.19 
Timing Profile 
Safety Population 
 
 
Page 154 of 
154 
 
Version 1.0 
26 Mar 2020 
 
 
 
 
 
 
 
 
Centre 
IPM 027 
Trial 
Date 
IPM 027 Participant 
End of Treatment Status 
    Participant ID 
Treatment 
 
Category 
ID 
 
 
 
 
 
 
 
Centre XX 
 
 
 
 
 
  XXXXXXXX 
Dapivirine / 
IPM 032 / 
Time on IP / 
XXXXXX 
Completed / 
 
Placebo 
IPM 027 
Time on open-label IP / 
 
Discomtinued: Xxxxxxxx / 
 
 
 
Time off IP / 
 
Etc. 
 
 
 
Total time on IP / 
 
 
 
 
 
Time off between IPM 027 and IPM 032 / 
 
 
 
 
 
Time on randomized IP / 
 
 
 
 
 
IPM 027 exit date / 
 
 
 
 
 
IPM 032 exit date 
 
 
 
 
 
Time to seroconversion / 
 
 
 
 
 
Time to first positive HIV RNA / 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


IPM 032 Statistical Analysis Plan 
Appendix 4 – Version 1.0, dated 02 April 2020 
Page 1 of 1 
Appendix 4 – Stanford HIV-1 Drug Resistance (database version 8.4 - 
dated 2017-06-16) 
 
Stanford Mutation List NNRTI Version 8.4 
NNRTI 
A98G, L100I, L100V, K101E, K101H, K101P, K103E, K103Q, K103H, K103N, K103S, K103T, 
V106A, V106M, V108I, E138A, E138K, E138Q, E138G, E138R, V179D, V179E, V179F, 
V179L, V179T, Y181C, Y181F, Y181S, Y181G, Y181I, Y181V, Y188C, Y188F, Y188H, 
Y188L, G190A, G190C, G190T, G190V, G190E, G190Q, G190S, H221Y, P225H, F227C, 
F227L, M230I, M230L, P236L, K238T, K238N, Y318F, N348I. 
 
Stanford Mutation List NRTI Version 8.4 
NRTI 
E40F, M41L, E44A, E44D, A62V, K65E, K65N, K65R, D67Deletion, D67G, D67E, D67S, 
D67T, D67H, D67N, S68Deletion, T69Deletion, T69D, T69G, T69Insertion, K70Deletion, 
K70E, K70G, K70Q, K70N, K70S, K70T, K70R, L74V, L74I, V75I, V75M, V75S, V75A, V75T, 
F77L, Y115F, F116Y, Q151L, Q151M, M184V, M184I, L210W, T215F, T215S, T215C, 
T215D, T215E, T215I, T215V, T215A, T215L, T215N, T215Y, K219N, K219R, K219Q, 
K219E, K219W. 
 
Stanford Mutation List PI Version 8.4 
Major 
D30N, V32I, L33F, M46I, M46L, I47A, I47V, G48M, G48V, I50L, I50V, I54A, I54T, I54L, I54M, 
I54V, L76V, V82A, V82F, V82L, V82T, V82S, I84V, N88S, N88D, L90M 
 
 
 


 
IPM 032 SAP, Appendix 5 
IPM 032 Adverse Events of Interest 
 
Version 1.0, 28Mar2019 
 
  
 
 
 
         Page 1 of 4 
System Organ Class (SOC) 
Preferred Term (PT) of Interest 
Lower Level Term (if applicable) 
Descriptive Term 
Infections and infestations 
Bacterial vaginosis 
N/A 
N/A 
 
Bartholin's abscess 
N/A 
N/A 
 
Vulval abscess 
N/A 
N/A 
 
Cervicitis 
N/A 
N/A 
 
Cystitis 
N/A 
N/A 
 
Genital infection female 
N/A 
N/A 
 
Genitourinary tract gonococcal infection 
N/A 
Gonococcal urogenital events 
 
Vulvovaginitis gonococcal 
 
 
 
Gynaecological chlamydia infection 
N/A 
Chlamydia urogenital events 
 
Vulvovaginitis chlamydial 
 
 
 
Oophoritis 
N/A 
N/A 
 
Pelvic inflammatory disease 
N/A 
N/A 
 
Pyelonephritis 
N/A 
N/A 
 
Syphilis 
N/A 
N/A 
 
Trichomoniasis 
N/A 
Trichomonal urogenital events 
 
Vulvovaginitis trichomonal 
 
 
 
Urinary tract infection 
N/A 
N/A 
 
Vaginal infection 
N/A 
N/A 


 
IPM 032 SAP, Appendix 5 
IPM 032 Adverse Events of Interest 
 
Version 1.0, 28Mar2019 
 
  
 
 
 
         Page 2 of 4 
System Organ Class (SOC) 
Preferred Term (PT) of Interest 
Lower Level Term (if applicable) 
Descriptive Term 
Infections and infestations (cont.) 
Vulval cellulitis 
N/A 
N/A 
 
Vulvovaginal candidiasis 
N/A 
N/A 
 
Vulvovaginitis 
N/A 
N/A 
Reproductive system and breast 
disorders 
Adnexa uteri cyst 
N/A 
Adnexa uteri symptoms 
Adnexa uteri mass 
 
 
 
Adnexa uteri pain 
 
 
 
Adnexa uteri pain 
 
 
 
Amenorrhoea 
N/A 
Bleeding disorders 
 
Menorrhagia 
 
 
 
Metrorrhagia 
 
 
 
Menstruation irregular 
 
 
 
Cervix disorder 
Cervix lesion*  
N/A 
 
Cervix inflammation 
Cervix inflammation**  
N/A 
 
Dysmenorrhoea 
N/A 
N/A 
 
Dyspareunia 
N/A 
N/A 
 
Ovarian mass 
N/A 
N/A 
 
Pelvic discomfort 
N/A 
N/A 
 
Pelvic pain 
N/A 
N/A 


 
IPM 032 SAP, Appendix 5 
IPM 032 Adverse Events of Interest 
 
Version 1.0, 28Mar2019 
 
  
 
 
 
         Page 3 of 4 
System Organ Class (SOC) 
Preferred Term (PT) of Interest 
Lower Level Term (if applicable) 
Descriptive Term 
Reproductive system and breast 
disorders (cont.) 
Pruritus genital 
N/A 
N/A 
Uterine cervix ulcer 
N/A 
N/A 
 
Uterine pain 
N/A 
N/A 
 
Uterine tenderness 
N/A 
N/A 
 
Vaginal discharge 
N/A 
N/A 
 
Vaginal odour 
N/A 
N/A 
 
Vaginal ulceration 
Vulval lesion* 
N/A 
 
Vulval disorder 
N/A 
N/A 
 
Vulval ulceration 
N/A 
N/A 
 
Vulvovaginal discomfort 
N/A 
N/A 
 
Vulvovaginal dryness 
N/A 
N/A 
 
Vulvovaginal pain 
N/A 
N/A 
 
Vulvovaginal pruritus 
N/A 
N/A 
 
Vulvovaginal rash 
N/A 
N/A 
 
Vulvovaginal swelling 
N/A 
N/A 
Renal and urinary disorders 
Bladder pain 
N/A 
N/A 
 
Dysuria 
N/A 
N/A 
 
Urine odour abnormal 
N/A 
N/A 


 
IPM 032 SAP, Appendix 5 
IPM 032 Adverse Events of Interest 
 
Version 1.0, 28Mar2019 
 
  
 
 
 
         Page 4 of 4 
System Organ Class (SOC) 
Preferred Term (PT) of Interest 
Lower Level Term (if applicable) 
Descriptive Term 
General disorders and 
administration site conditions 
Application site pain 
N/A 
N/A 
Suprapubic pain 
N/A 
N/A 
Neoplasms benign, malignant and 
unspecified (incl cysts and 
polyps) 
Anogenital warts 
N/A 
N/A 
Uterine leiomyoma 
N/A 
N/A 
 
Vulvovaginal warts 
N/A 
N/A 
Pregnancy, puerperium and 
perinatal conditions 
Abortion spontaneous 
N/A 
N/A 
Abortion spontaneous incomplete 
N/A 
N/A 
 
Retained products of conception 
N/A 
N/A 
*IPM convention for vesicular ulcerative lesion 
**The reported term for the AE was “Granuloma in cervical os due to gynaecological infection” 


 
Page 1 of 5 
IPM 032 Protocol Version 2.0 Amendment 2.0 
Sections to be implemented  
 
Version 2.0 Date: 27Jun 2018 
Sections in Protocol Version 2.0 Amendment 2.0 dated 16 Jan 2017 to be implemented  
 
NOTE: Text highlighted in this document is the text in the specific sections that will be implemented with regards to Amendment 2.0. 
These sections will be implemented in addition to the Protocol Version 2.0 Amendment 1.0 dated 22 Oct 2015 that is currently 
implemented at the research centres in its entirety. 
 
Sections: 
 
Protocol Synopsis 
 
The Exploratory Trial Objectives are: 
1. To assess the feasibility of 3-monthly follow-up visits, as a possible schedule for post-licensure vaginal ring clinical follow-up 
2. To explore the correlation between drug concentrations and results from the visual inspection of the returned vaginal rings by 
research staff between the monthly and 3-monthly research centre follow-up schedules 
3. To determine the proportion of participants electing to undergo HIV rapid tests at the research centres between scheduled 3- 
monthly visits 
4. To characterize the IPM 027 participants who decline enrollment into IPM 032 (Decliner Population) 
5. To explore self-reported acceptability of and adherence to the 25 mg Dapivirine Vaginal Ring-004. 
 
The exploratory endpoints are: 
 
 
Feasibility of 3-monthly clinical follow-up schedule 
 
Dapivirine residual amounts in returned used vaginal rings and/or dapivirine concentrations in blood and/or vaginal fluid in 
correlation with results from the visual inspection of the returned used vaginal rings by research staff 
 
Proportion of participants opting for HIV rapid tests at the research centre between scheduled 3-monthly research centre 
follow-up visits 
 
Characteristics of IPM 027 participants who decline enrollment into IPM 032 (Decliner Population) and reasons for declining 
 
The proportion of women who report the use of the vaginal ring as acceptable 
 
Participant self-reported patterns of ring use 
 
 


 
Page 2 of 5 
IPM 032 Protocol Version 2.0 Amendment 2.0 
Sections to be implemented  
 
Version 2.0 Date: 27Jun 2018 
The exploratory endpoints will be assessed through: 
 
Participant report of feasibility regarding a 3-monthly clinical follow-up schedule (Participant Questionnaire) 
 
Number of women opting not to receive two additional rings at the 3-monthly visits 
 
Proportion of returned rings (used and unused) during the 3-monthly clinical follow-up schedule 
 
Dapivirine residual amounts in returned used vaginal rings and/or dapivirine concentrations in blood and/or vaginal fluid 
 
Visual inspection of the returned used vaginal rings by  research centre staff 
 
Number of participants undergoing HIV rapid tests at the research centre between scheduled 3-monthly research centre 
follow-up visits 
 
Questionnaires and qualitative data regarding reasons for declining participation, ring acceptability and self-reported patterns 
of ring use. 
 
 
METHODS: 
Qualitative and Quantitative Behavioural Assessments: 
Each research centre will conduct two to three in-depth individual interviews (IDIs) with approximately six participants in each of the 
following categories: 
 
Decliner Population 
 
Ring Users 
 
Ring Non-users 
In cases of interest IDIs will be conducted; approximately three participants will be interviewed per site. These cases of interest 
may include, but will not be limited to participants who may have experienced social harms, may have had problems using the ring, 
or who HIV seroconverted.  
 
Focus group discussions may be conducted with the above mentioned groups. Efforts will be made to ensure the sample size 
is representative of both previous IPM 027 participants as well as the two ring-naïve cohorts of women. Additionally, IDIs and/or 
FGDs with approximately six males from the community and/or male partners will be conducted at each research centre. 
 
DVR-naïve participants will complete a behavioural questionnaire at enrolment, in addition to the participant questionnaire collected 
at other trial visits. 
 


 
Page 3 of 5 
IPM 032 Protocol Version 2.0 Amendment 2.0 
Sections to be implemented  
 
Version 2.0 Date: 27Jun 2018 
These assessments will provide data on acceptability and influencers of ring use. The recruitment and sampling strategy will be 
specified in the study operations manual. 
 
2.2. Trial Endpoints and Assessments 
 
The Exploratory Trial Objectives are: 
 
1. To assess the feasibility of 3-monthly follow-up visits, as a possible schedule for post-licensure vaginal ring clinical follow-up 
2. To explore the correlation between drug concentrations and results from the visual inspection of the returned vaginal rings by 
research staff between the monthly and 3-monthly research centre follow-up schedules 
3. To determine the proportion of participants electing to undergo HIV rapid tests at the research centres between scheduled 3- 
monthly visits 
4. To characterize the IPM 027 participants who decline enrollment into IPM 032 (Decliner Population) 
5. To explore self-reported acceptability of and adherence to the 25 mg Dapivirine Vaginal Ring-004. 
 
The exploratory endpoints are: 
 
 
Feasibility of 3-monthly clinical follow-up schedule 
 
Dapivirine residual amounts in returned used vaginal rings and/or dapivirine concentrations in blood and/or vaginal fluid in 
correlation with results from the visual inspection of the returned used vaginal rings by research staff 
 
Proportion of participants opting for HIV rapid tests at the research centre between scheduled 3-monthly research centre 
follow-up visits 
 
Characteristics of IPM 027 participants who decline enrollment into IPM 032 (Decliner Population) and reasons for declining 
 
The proportion of women who report the use of the vaginal ring as acceptable 
 
Participant self-reported patterns of ring use 
 
The exploratory endpoints will be assessed through: 
 
 
Participant report of feasibility regarding a 3-monthly clinical follow-up schedule (Participant Questionnaire) 
 
Number of women opting not to receive two additional rings at the 3-monthly visits 
 
Proportion of returned rings (used and unused) during the 3-monthly clinical follow-up schedule 
 
Dapivirine residual amounts in returned used vaginal rings and/or dapivirine concentrations in blood and/or vaginal fluid 


 
Page 4 of 5 
IPM 032 Protocol Version 2.0 Amendment 2.0 
Sections to be implemented  
 
Version 2.0 Date: 27Jun 2018 
 
Visual inspection of the returned used vaginal rings by  research centre staff 
 
Number of participants undergoing HIV rapid tests at the research centre between scheduled 3-monthly research centre 
follow-up visits 
 
Questionnaires and qualitative data regarding reasons for declining participation, ring acceptability and self-reported patterns 
of ring use. 
5.16 Qualitative Behavioural Assessments 
 
 
Each research centre will conduct two to three in-depth individual interview (IDIs) with approximately six participants in each of the 
following categories:  
 
Decliner Population  
 
Ring Users 
 
Ring Non-users 
 
In cases of interest IDIs will be conducted; approximately three participants will be interviewed per site. These cases of interest may 
include, but will not be limited to participants who may have experienced social harms, may have had problems using the ring, or who 
HIV seroconverted 
 
Focus group discussions may also be conducted with the above mentioned groups. Efforts will be made to ensure the sample size is 
representative of both previous IPM 027 participants as well as the two ring-naïve cohorts of women. Additionally, IDIs and/or FGDs 
with approximately six males from the community and/or male partners will be conducted at each research centre.  
 
DVR-naïve participants will complete a behavioural questionnaire at enrolment, in addition to the participant questionnaire collected 
at other trial visits. 
 
These assessments will provide data on acceptability and influencers of ring use. The recruitment and sampling strategy will be specified 
in the study operations manual. 
 
 
 
 
 


 
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IPM 032 Protocol Version 2.0 Amendment 2.0 
Sections to be implemented  
 
Version 2.0 Date: 27Jun 2018 
 
8.4.5 Other results from Qualitative/Quantitative Behavioural assessments 
 
 
Each research centre will conduct two to three in-depth individual interviews (IDIs) with approximately six participants in each of the 
following categories:  
Decliner Population  
Ring Users 
Ring Non-users 
 
In cases of interest IDIs will be conducted; approximately three participants will be interviewed per site. These cases of interest may 
include, but will not be limited to participants who may have experienced social harms, may have had problems using the ring, or 
who HIV seroconverted. Focus group discussions may be conducted with the above mentioned groups. Efforts will be made to 
ensure the sample size is representative of both previous IPM 027 participants as well as the two ring-naïve cohorts of women. 
Additionally, IDIs and/or FGDs with approximately six males from the community and / or male partners will be conducted at each 
research centre.  
 
DVR-naïve participants will complete a behavioural questionnaire at enrolment, in addition to the participant questionnaire collected 
at other trial visits.  
 
8.5 Data and Safety Monitoring Board 
 
Safety data from the trial will be evaluated by an independent Data and Safety Monitoring Board (DSMB). The first scheduled 
meeting will take place approximately six months after all research centres have been activated and thereafter at approximately 
annual intervals for the duration of IPM 032. Based on the review of the data, the DSMB is required to provide recommendations 
about continuation, pausing, termination or other modifications to the trial, including changes to the information provided to 
participants for obtaining their informed consent. An IPM 032 DSMB charter will describe the roles and responsibilities of the DSMB, 
its composition, data to be provided to the DSMB, the process for disseminating trial data to the DSMB, and the communication 
plan between the DSMB and IPM. 
 


 
Protocol Deviation Criteria 
Protocol IPM 032 
 
 
Author: Winel Mans 
IPM 032 Protocol Deviation Criteria V1.0, 10Nov2016  
 
 
 
 
 
 
 
Page 1 of 6 
 
 
Deviation Category 
Description 
Classification 
Comment 
1 
Inappropriate 
enrolment 
 
 
 
 
 
 
More than one Inclusion or Exclusion criterion not met. 
Major 
 
Inclusion Criteria: 
 
Inclusion criterion 1:  Previously enrolled in the IPM 027 
trial 
Major 
 
Inclusion criterion 2:  Available for all visits and consent to 
follow all procedures scheduled for the trial 
 
To review   
 
Inclusion criterion 3:    Using an effective method of 
contraception at the Enrolment Visit, and intending to use 
an effective contraceptive method for the duration of trial 
participation, unless post-menopausal with no history of 
menses for one year prior to screening. 
Major 
 
Inclusion criterion 4: HIV-negative as determined by the 
HIV algorithm applied at Screening/Pre-Enrolment 
 
Major 
 
Inclusion criterion 5:  Willing to refrain from participation in 
another research trial using drugs, vaccines, medical 
devices and microbicides for the duration of the IPM 032 
trial 
 
Major 
 
Inclusion criterion 6: Willing to provide adequate locator 
information for trial retention purposes and be reachable 
per local standard procedures (e.g., by home visit or 
telephone; or via family or close neighbour contacts); 
confidentiality to be maintained 
Minor 
 


 
Protocol Deviation Criteria 
Protocol IPM 032 
 
 
Author: Winel Mans 
IPM 032 Protocol Deviation Criteria V1.0, 10Nov2016  
 
 
 
 
 
 
 
Page 2 of 6 
 
 
Deviation Category 
Description 
Classification 
Comment 
 
 
 
Exclusion Criteria: 
 
Exclusion criterion 1: Investigational product use 
permanently discontinued in response to an AE (where 
the AE was considered related to investigational product) 
or safety-related concern while taking part in the IPM 027 
trial 
Major 
 
Exclusion criterion 2: Participant self-report of taking post-
exposure prophylaxis (PEP)within ≤ 2 months at 
Screening Visit  Note: Participants may be enrolled after 
completing the PEP regimen and a negative HIV test was 
documented at least 2 months prior to screening for IPM 
032 
 
To  review 
 
Exclusion criterion 3: Currently pregnant,  or currently 
breast-feeding 
Major 
 
 
 
Intends to become pregnant 
To review 
 
 Exclusion criterion 4: Known drug abuse or alcohol 
dependence in the 12 months prior to screening 
 
To review 
 
Exclusion criterion 5: Participated in another research trial 
(other than IPM 027) using drugs, medical devices, 
microbicides or oral pre-exposure prophylaxis agents 
within 30 days prior to screening 
 
 
To review 
 
 
 
Exclusion criterion 6: Any new illness or condition(s), 
chronic condition(s) or abnormal laboratory finding(s) that, 
in the opinion of the investigator, might put the participant 
at risk, or interfere with the trial objectives or the 
 
To review 
 


 
Protocol Deviation Criteria 
Protocol IPM 032 
 
 
Author: Winel Mans 
IPM 032 Protocol Deviation Criteria V1.0, 10Nov2016  
 
 
 
 
 
 
 
Page 3 of 6 
 
 
Deviation Category 
Description 
Classification 
Comment 
participant’s adherence to trial requirements 
2 
Missed visit  
 
 
To Review 
 
3 
Visit completed 
outside of 
permissible windows 
 
To review 
 
4 
Informed consent 
process deviations  
 
 
To review 
Deviations will be discussed on a case-by-case 
basis, and the severity will be determined by the 
nature of the deviation. Absence of documented 
informed consent prior to trial related procedures 
will be considered major. 
 
5 
IP deviations  
(dispensing, timing and 
dosing  
IP incorrectly dispensed and used by participant  
 
Major 
 
Expired IP dispensed and used by participant  
 
Major 
 
Quarantined/not fit for use IP dispensed and used by 
participant  
 
Major 
Occurrence and extent of temperature excursions, 
for example, to be evaluated on a case-by-case 
basis. 
 
6 
Safety Reporting  
(IREs not reported 
within timeframe, 
unreported AEs)  
SAE not reported within 24 hours 
Minor 
 
For definition of PP population this would be 
considered minor (i.e. participant would not be 
excluded from PP population) as the deviation does 
not have effect on data). 
Multiple unreported AEs for the same participant 
 
To be reviewed 
 
Any non-serious AE leading to permanent discontinuation 
of the IP not reported  within 48 hours 
 
Minor 
 
Seroconversion not reported within 48 hours 
 
Minor 
 
Pregnancy not reported within 48 hours 
Minor 
 


 
Protocol Deviation Criteria 
Protocol IPM 032 
 
 
Author: Winel Mans 
IPM 032 Protocol Deviation Criteria V1.0, 10Nov2016  
 
 
 
 
 
 
 
Page 4 of 6 
 
 
Deviation Category 
Description 
Classification 
Comment 
7 
Failure to discontinue 
(temporarily or 
permanently) IP use 
for whom it is 
indicated  
 
HIV Seroconversion  
 
Minor 
For definition of PP population this would be 
considered minor (i.e. participant would not be 
excluded from PP population) as the deviation 
occurred after the seroconversion (endpoint). 
Pregnancy 
Major 
 
SAE or non-serious AE (including laboratory abnormality) 
indicating need for IP discontinuation  
 
Major 
 
8 
Inappropriate 
treatment/ 
management of 
medical conditions 
and follow-up of AEs  
 
 
To review 
Deviation will be discussed on a case-by-case 
basis, and the severity will be determined by the 
nature of the deviation 
9 
Mishandled laboratory 
samples (including 
samples that have been 
collected, processed, 
stored or transported 
incorrectly)  
 
Incorrectly labelled samples, resulting in redraw  
 
 
Minor 
 
Incorrect storage (e.g. loss of cold chain with loss of 
samples)  
 
 
Minor 
 
Incorrect sampling (preservative contamination)  
 
 
Minor 
 
Data not recorded, resulting in loss of data (tear strip 
weight not recorded; rapid test result not recorded on log)  
 
 
Minor 
 
Lost samples (storage/shipping)  
 
 
Minor 
 
10 
Missing or incorrectly 
timed trial 
procedures  
 
Pregnancy tests not performed as per protocol schedule  
 
To review 
 
Other trial procedures not performed as per protocol 
schedule.  
 
To review 
 


 
Protocol Deviation Criteria 
Protocol IPM 032 
 
 
Author: Winel Mans 
IPM 032 Protocol Deviation Criteria V1.0, 10Nov2016  
 
 
 
 
 
 
 
Page 5 of 6 
 
 
Deviation Category 
Description 
Classification 
Comment 
11 
Conduct of additional 
non-study related 
procedures  
 
 
To review 
Deviation will be discussed on a case-by-case 
basis, and the severity will be determined by the 
nature of the deviation 
12 
Participant non-
adherence to trial 
requirements  
 
Participant fails to follow protocol requirements which are 
deemed to be serious enough by the Investigator to 
warrant discontinuation, e.g. in the absence of an AE or 
discomfort, participant refuses to keep vaginal ring 
inserted for the duration of the relevant treatment period  
 
To review 
 
13 
Failure to discontinue 
participants who 
meet trial 
discontinuation 
criteria  
 
Participant withdraws her consent  
 
Major 
 
Participant tests HIV-positive according to the HIV-testing 
algorithm 
Minor 
 
 
Participant is lost to follow-up, i.e. the research centre is 
unsuccessful (following reasonable attempts as defined in 
the local SOP) in contacting participant or bringing the 
participant back to the research centre l 
 
Minor 
If for safety reasons, the Investigator considers it in the 
best interest of the participant to discontinue her from the 
trial  
 
To review 
 
For laboratory values: Major in cases where 
investigator has indicated the findings to be related 
to IP. 
At the discretion of the Investigator, IPM, the relevant 
Institutional Review Board/Independent Ethics Committee 
(IRB/IEC), or the government health authority  
 
Minor 
 
14 
Other, specify  
 
 
To review 
 
 
 
 




IPM 032 
Statistical Analysis Plan Virology Addendum, Version 1.0 
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CONFIDENTIAL 
 
 
 
Statistical Analysis Plan 
Virology Addendum Analysis of  
Dapivirine Vaginal Ring-004 Clinical Trial 
IPM 032 
(Phase IIIb Clinical Trial) 
Version 1.0 
International Partnership for Microbicides 
8405 Colesville Road, Suite 600 
Silver Spring, MD 20910 USA 
 


IPM 032 
Statistical Analysis Plan Virology Addendum, Version 1.0 
Version Dated: 24 May 2021 
Page 2 of 18 
 
 
CONFIDENTIAL 
 
 
APPROVAL SIGNATURE PAGE 
IPM 032 Virology Addendum – Statistical Analysis Plan 
I have read the above referenced Statistical Analysis Plan and approve its contents. 
 
 
 
 
 
_________________________ 
John Steytler, MBChB 
Head of Pharmacovigilance and Clinical 
Development 
International Partnership for Microbicides 
 
 
 
 
 
_________________________ 
Ben Van Baelen, MSc 
Statistical consultant 
BVB Clin Consult BVBA 
 
 
 
 
 
_________________________ 
Neliëtte van Niekerk, MCom 
Senior Director Biometrics 
International Partnership for Microbicides 


IPM 032 
Statistical Analysis Plan Virology Addendum, Version 1.0 
Version Dated: 24 May 2021 
Page 3 of 18 
 
 
CONFIDENTIAL 
 
 
APPROVAL SIGNATURE PAGE 
IPM 032 Virology Addendum – Statistical Analysis Plan 
I have read the above referenced Statistical Analysis Plan and approve its contents. 
 
 
 
 
 
 
_________________________ 
Charles Craig, PhD 
Virology Consultant 
International Partnership for Microbicides 
 
 
 
 
 
_________________________ 
John Mellors, MD 
Professor of Medicine  
Division of Infectious Diseases  
University of Pittsburgh 
 


IPM 032 
Statistical Analysis Plan Virology Addendum, Version 1.0 
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CONFIDENTIAL 
 
 
ABBREVIATIONS 
CSR 
Clinical Study Report 
DNA 
Deoxyribonucleic acid 
DVR-004 
Dapivirine Vaginal Ring-004 
EFV 
Efavirenz 
ETR 
Etravirine 
FC 
Fold-change 
HIV-1 
Human immunodeficiency virus type 1 
HIVdb 
HIV Drug Resistance Database 
IC50 
50% inhibitory concentration 
IP 
Investigational product (ie, the DVR-004 and placebo ring) 
IPM 
International Partnership for Microbicides 
ITT 
Intent-to-treat 
MTN 
Microbicide Trials Network 
NGS 
Next generation sequencing 
NNRTI 
Non-nucleoside reverse transcriptase inhibitor 
NVP 
Nevirapine 
PCR 
Polymerase chain reaction 
RAM 
Resistance-associated mutation 
RNA 
Ribonucleic acid 
RPV 
Rilpivirine 
RT 
Reverse transcriptase 
SAP 
Statistical Analysis Plan 
STI 
Sexually transmitted infection 
T&L 
Tables and Listings 
UMI 
Unique molecular identifier 
USA 
United States of America 
 


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Statistical Analysis Plan Virology Addendum, Version 1.0 
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CONFIDENTIAL 
 
 
TABLE OF CONTENTS 
APPROVAL SIGNATURE PAGE .............................................................................. 2 
ABBREVIATIONS ...................................................................................................... 4 
TABLE OF CONTENTS .............................................................................................. 5 
1. 
INTRODUCTION ..................................................................................... 6 
2. 
OBJECTIVE .............................................................................................. 7 
2.1. 
Endpoints ................................................................................................... 7 
2.2. 
Assessments of Endpoints ......................................................................... 7 
3. 
ANALYSIS POPULATIONS ................................................................... 9 
3.1. 
Safety Population ....................................................................................... 9 
3.2. 
Virology Population ................................................................................... 9 
4. 
GENERAL STATISTICAL CONSIDERATIONS ................................. 10 
4.1. 
Analysis Software .................................................................................... 10 
4.2. 
Planned Subgroups .................................................................................. 10 
4.3. 
Data Used for Analysis ............................................................................ 10 
4.4. 
Methods for Handling Missing Data ....................................................... 10 
5. 
ANALYSIS OF DEMOGRAPHIC AND BASELINE 
CHARACTERISTICS ............................................................................. 11 
6. 
ANALYSIS OF GENOTYPING DATA ................................................. 12 
6.1. 
Definition of Resistance-associated Mutations ....................................... 12 
6.2. 
Population-based Sequencing .................................................................. 12 
6.3. 
Next Generation Sequencing ................................................................... 12 
6.4. 
Phenotypic Susceptibility ........................................................................ 13 
7. 
REFERENCES ........................................................................................ 14 
8. 
APPENDICES ......................................................................................... 15 
8.1. 
Appendix 1 – Tables and Listings Titles ................................................. 15 
8.2. 
Appendix 2 – Stanford Human Immunodeficiency Virus Type 1 Drug 
Resistance (Database Version 8.4 Provided by Stanford HIVdb) ........... 16 
8.3. 
Appendix 3 – Stanford Non-nucleoside Reverse Transcriptase Inhibitor 
Resistance Mutation Scores (Database Version 8.4, dated 18 July 2018)
 ................................................................................................................. 17 
 


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1. 
INTRODUCTION 
This document serves as the Statistical Analysis Plan (SAP) for the supplementary virology 
analysis of the Dapivirine Vaginal Ring-004 (DVR-004) Phase IIIb open-label extension trial, 
IPM 032. Specifically, this document describes the process for identification of samples and 
statistical methods that will be used to analyze the data resulting from retrospective resistance 
testing using a unique molecular identifier (UMI) next generation sequencing (NGS) 
methodology1-3, as well as phenotypic susceptibility analysis recombinant retroviral system4. 
There are several advantages of the NGS method employed in this analysis over standard 
NGS methodologies. The current methodology uses UMI ‘barcodes’ built into polymerase 
chain reaction (PCR) primers, which allows sequences originating from the same human 
immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) template to be grouped and 
aligned. Building consensus sequences from these alignments provides improved control of 
PCR and sequencing error, PCR bias, and PCR recombination. The number of UMI with 
consensus sequences allows the depth of sequencing to be calculated based on the number of 
HIV-1 RNA templates sampled, which can in turn be used to estimate the sensitivity of the 
individual sample analysis using an adaptation of the Clarke and Carbon equation 
[P=1-(1-f)N  
where P = probability, N = number of sequences, f = fraction of sequences with variant]5,6 to 
obtain the proportion of a minority species that can be detected with 95% confidence. The 
assay has been validated to detect resistance-associated mutations (RAMs) down to 1% 
prevalence, subject to the number of consensus sequences (UMIs) observed. Despite the 
robust nature of the assay and the analysis of its results, the NGS analysis should still be 
considered as exploratory. Of note, clinical interpretation of these data remains challenging. 
In addition to technical challenges, there is an absence of cross-laboratory standardization of 
outputs and of accredited means for external quality assessment7,8. In the absence of 
resolution of these issues, the clinical relevance of the increased sensitivity for detection of 
resistance-associated mutations using NGS remains unknown. 
Templates for all tables and listings that will be used to present the virology results are also 
provided. These analyses will be described in an addendum to the IPM 032 Clinical Study 
Report (CSR). 
Table shells and listing shells that will accompany the analyses are provided in a separate 
document of mock tables and listings (T&L) (Appendix 1). This document is viewed as 
supporting material for the analyses and will not require signature approval if formatting 
changes are made. 


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2. 
OBJECTIVE 
The primary purpose of this analysis is to further address, with supplementary information, 
the secondary objective for trial IPM 032: 
• To assess the frequency of HIV-1 drug resistance in women who acquire HIV-1 
infection while using the DVR-004. 
Specifically, the analyses will facilitate the description of: 
• the prevalence of all variants detectable to a minimum prevalence of 1%, 5%, or 
10% in reverse transcriptase (RT) at seroconversion using NGS. 
• the fold-change (FC) in phenotypic susceptibility of virus at seroconversion to 
dapivirine, efavirenz, etravirine, nevirapine, and rilpivirine relative to a wild-type 
control. 
• the findings in relation to the population-based genotyping results described in the 
IPM 032 CSR and the Phase III Clinical Virology Report Version 4.0. 
2.1. 
Endpoints 
Primary Endpoints: 
• The presence of non-nucleoside reverse transcriptase inhibitor (NNRTI) 
resistance-associated mutations (RAMs), including minority species RAMS at 
seroconversion, using NGS. 
• Phenotypic susceptibility of virus to dapivirine and the approved NNRTIs: 
efavirenz, etravirine, nevirapine and rilpivirine, measured at seroconversion. 
Secondary Endpoint: 
• Comparison of specific NNRTI RAM detection using population-based 
genotyping and NGS. 
Exploratory Endpoints: 
• Correlation between phenotypic susceptibility findings and population-based 
genotype. 
• Longitudinal NGS-based genotyping of virus from one selected participant with 
emergence of K103N determined using population-based genotyping (Participant 
Identifier 3201198). 
2.2. 
Assessments of Endpoints 
Primary Endpoints Assessed by: 
• Determination of the prevalence of all variants reported from NGS tests with 
sensitivity to detect viruses present at ≥ 10.0%, ≥ 5.0%, and ≥ 1.0% prevalence 
in HIV-1 RT at seroconversion. 
• Determination of the 50% inhibitory concentration (IC50) and FC in phenotypic 
susceptibility of virus at seroconversion to dapivirine, efavirenz, etravirine, 
nevirapine, and rilpivirine relative to a wild-type control virus. 


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Secondary Endpoint Assessed by: 
• Summarizing numbers and prevalence of additional NNRTI RAMs observed 
using NGS compared with population-based genotyping, within the limits of the 
NGS sequence region (reverse transcriptase codons 81 to 149 and 152 to 212). 
Exploratory Endpoints Assessed by: 
• Summarizing viral fold-change in susceptibility to dapivirine by mutation patterns 
determined using population-based genotyping assessment. 
• Comparison of IC50 values between viruses with known NNRTI RAMs and those 
with wild-type genotypes. 
• Comparison of pre-seroconversion and seroconversion NGS analyses in samples 
from participant with emergent K103N at seroconversion (Participant 
Identifier 3201198). 
 


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3. 
ANALYSIS POPULATIONS 
3.1. 
Safety Population 
The safety population includes all trial participants who were enrolled from the parent trial, 
IPM 027, and received and inserted at least one DVR-004. 
3.2. 
Virology Population 
The virology population includes all participants in the safety population who experienced 
seroconversion (either using HIV-1 Rapid test result algorithms or determined to have been 
HIV-1 infected while using the DVR-004 based on reverse sequential HIV-1 RNA PCR 
testing) during investigational product (IP) use except: 
• Participants who were deemed to be HIV-1 RNA positive at the time of 
enrolment. 
• Participants who seroconverted after last product use (ie, at the Exit Visit) and 
were not HIV-1 RNA positive at the last product use visit, ie, were infected after 
they discontinued product use. 
The virology population will be the main focus of this analysis. Available data for any 
participants infected with HIV-1 prior to enrolment or after last product use will be listed and 
described separately. Phenotypic analyses will be performed only on samples obtained at 
seroconversion during DVR-004 use. 


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4. 
GENERAL STATISTICAL CONSIDERATIONS 
4.1. 
Analysis Software 
Statistical analyses will be conducted by an external service provider of the International 
Partnership for Microbicides (IPM) and will be reviewed by IPM and the University of 
Pittsburgh Virology Laboratory. The analyses will be performed using SAS® for Windows 
or Linux/Unix (Version 9.2 or higher, SAS Institute Inc., Cary, North Carolina, United States 
of America [USA]). 
4.2. 
Planned Subgroups 
As numbers are small, there are no plans to perform analyses in subgroups. Should individual 
outlier results be observed, additional relevant characteristics may be described from the 
IPM 032 CSR listings or listings from this addendum. 
4.3. 
Data Used for Analysis 
Next generation sequencing will be attempted for all available seroconversion samples from 
all participants in the virology population, although results showing sensitivity to detect 
viruses present only at >10.0% prevalence (ie, with detection of < 28 UMI) will be 
summarized, although, due to inadequate sensitivity, these results will not be used to infer the 
absence of NNRTI RAMs. Analyses will be performed with cut-offs set to include the 
detection of minority species present in at least 10.0%, 5.0%, or 1.0% of UMI. 
Results showing sensitivity to detect only minority species present with > 10.0% prevalence 
(ie, UMI < 28) will be described individually. 
Phenotypic susceptibility and NGS will be performed on plasma samples taken at the time of 
HIV-1 seroconversion ± 14 days. Any results from other time points will be listed and may 
be discussed separately, but not included in summary analyses. 
4.4. 
Methods for Handling Missing Data 
While every effort will be made to minimize the amount of missing data, as this is a 
retrospective analysis, some degree of missing data associated with sample availability and 
participant consent, is expected. Numbers of missing analyses will be provided along with 
numbers of participants included in the analysis, and tests conducted with and without 
successful outcomes. 
If the date of the last IP exposure (ie, last ring removal) is incomplete or missing, the 
following imputation will be made: 
• when only the day is missing, impute with min (last ring insertion date + 28 days, 
last day of the month), else 
• impute with last ring insertion date + 28 days. 
This should be added in a footnote in the applicable tables/listings. If the date itself should be 
printed, the original (not the imputed) date should be printed. 


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5. 
ANALYSIS OF DEMOGRAPHIC AND BASELINE 
CHARACTERISTICS 
As numbers are small, the demographic and baseline characteristics of participants in the 
virology population will not be described. The overall population characteristics are available 
in the IPM 032 CSR Version 1.0. 


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6. 
ANALYSIS OF GENOTYPING DATA 
Antiretroviral drug NNRTI RAMs in virus from women who acquire HIV-1 while using the 
DVR-004 will be determined by means of NGS. (Population-based genotypes are reported in 
the IPM 032 CSR Version 1.0, dated 09 April 2020 and the Clinical Virology Report, 
Version 4.0.) Next generation sequencing provides the supplementary, exploratory results 
primarily addressed in the current SAP. 
6.1. 
Definition of Resistance-associated Mutations 
Summary analyses of NNRTI RAMs will be based on mutations identified in the Stanford 
HIV Drug Resistance Database (HIVdb) Version 8.4 (dated 16 June 2017, 
https://hivdb.stanford.edu/)9. The NNRTI RAMs with scores in the Stanford HIVdb 
algorithm Version 8.4 within the range of the NGS test include: 
A98G, L100I, L100V, K101E, K101H, K101P, K103H, K103N, K103S, K103T, V106A, 
V106M, V108I, E138A, E138G, E138K, E138Q, E138R, V179D, V179E, V179F, V179L, 
V179Ta, Y181C, Y181F, Y181G, Y181I, Y181S, Y181V, M184Ia, Y188C, Y188F, Y188H, 
Y188L, G190A, G190C, G190E, G190Q, G190S, G190T, G190V (Appendix 2). 
In addition, a summary of all amino acid variants from the reference sequence will be 
provided for both sequencing methodologies. 
6.2. 
Population-based Sequencing 
Population-based sequencing results at seroconversion have been described in the IPM 032 
CSR (IPM 032 CSR Version 1.0, dated 09 April 2020) and in the Clinical Virology Report, 
Version 4.0; individual participant results are provided in the listings associated with the 
IPM 032 CSR. 
The population-based genotyping sequences and resistance predictions will also be used to 
examine consistency with the NGS findings and the phenotypic susceptibility results. The 
reference sequence for the population-based sequencing analysis was the Stanford HIVdb 
consensus subtype B sequence. 
6.3. 
Next Generation Sequencing 
For NGS, the wild-type subtype B sequence, HXB2 (accession number K03455-1), will be 
used as reference. In the region sequenced, the only difference from the Stanford HIVdb 
consensus subtype B sequence is at codon 122 (HXB2: K122; Stanford: E122, respectively); 
K122 (or E122K) and E122 (or K122E) will be considered to be polymorphisms not related 
to NNRTI resistance in the analysis. The sensitivity for each NGS determination indicates the 
required prevalence for changes from the reference sequence to be detectable in the sample. 
The prevalences required are determined based on the statistical consideration of requiring at 
least 298 UMI for sensitivity to detect a 1.0% minority, 58 UMI for a 5.0% minority and 
28 UMI for a 10.0% minority and will be summarized in tabulations. Samples with results 
showing less than 298, 58 or 28 UMI will be censored from each analysis performed to 
sensitivities to detect 1.0%, 5.0%, and 10.0% minority species, respectively. 
 
a 
These mutations do not have a resistance score when present alone; V179T with Y181C and M184I with 
K101E contribute to the score as a combination. 


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Frequency tabulations per minimum detectable prevalence (1.0%, 5.0%, 10.0%), as well as 
any additional NNRTI RAMs observed when results indicate UMI < 28, will be presented 
showing the percentage of participants with an amino acid change from reference at each 
position of the sequenced RT region. 
All NGS results will be listed relative to the reference virus’ amino acid sequence together 
with percent prevalence in the sample. 
Frequency tabulations will be created per sensitivity cut-off (1.0%, 5.0%, 10.0%) for: 
• The number (and percentage) of participants who had a resistance test performed. 
• The number (and percentage) of participants with each individual NNRTI RAM. 
• The number (and percentage) of participants with 0, 1, 2 or ≥ 3 mutations by class 
(NNRTI). 
• The number (and percentage) of participants with combinations of specified 
NNRTI RAMs. 
6.4. 
Phenotypic Susceptibility 
Phenotyping data will be obtained for virus from women with HIV-1 seroconversion and who 
had a seroconversion sample with sufficient HIV-1 RNA for analysis. 
Recombinant HIV-1 will be generated containing cloned RT from the participant’s HIV-1 
RNA from plasma that was sampled at the time of HIV seroconversion. Recombinant viruses 
will be tested in the TZM-bl cell line for susceptibility to dapivirine as well as to the 
NNRTIs: efavirenz, etravirine, nevirapine, and rilpivirine. 
For each NNRTI, susceptibility will be reported as the half maximal inhibitory concentration 
(IC50). Fold-change resistance will be calculated for each individual NNRTI as: 
FC = IC50/IC50control 
• with IC50control = reference wild-type virus value or the geometric mean of results 
from the nearest match wild-type viruses in the analysis. The reference wild-type 
virus will be a recombinant virus with an anonymized HIV-1 RT amplicon from 
South Africa with no RT resistance-associated mutations cloned into an xxLAI 
vector (4). 
• when more than one IC50 value is available for a sample (replicate test results), the 
geometric mean IC50 value of all replicates will be taken prior to the FC 
calculation. 
Descriptive statistics of IC50 and FC values will be presented for each NNRTI and will 
include geometric mean and standard deviation, median, quartiles, range, and number of 
observations. 
Additionally, descriptive statistics (geometric mean and standard deviation) of NNRTI FCs 
will be presented by NNRTI RAM pattern. 
All individual participant data (IC50, FC) will be listed. Individual IC50 determinations and 
FCs will be averaged using geometric means for each virus when multiple determinations are 
available. 


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7. 
REFERENCES 
1. Zhou S, Jones C, Mieczkowski P, Swanstrom R. Primer ID Validates Template 
Sampling Depth and Greatly Reduces the Error Rate of Next-Generation Sequencing 
of HIV-1 Genomic RNA Populations. Journal of virology. 2015;89(16):8540-55. 
2. Keys JR, Zhou S, Anderson JA, Eron JJ, Jr., Rackoff LA, Jabara C, et al. Primer ID 
Informs Next-Generation Sequencing Platforms and Reveals Preexisting Drug 
Resistance Mutations in the HIV-1 Reverse Transcriptase Coding Domain. AIDS 
research and human retroviruses. 2015;31(6):658-68. 
3. Boltz VF, Rausch J, Shao W, Hattori J, Luke B, Maldarelli F, et al. Ultrasensitive 
single-genome sequencing: accurate, targeted, next generation sequencing of HIV-1 
RNA. Retrovirology. 2016;13(1):87. 
4. Shi C, Mellors JW. A recombinant retroviral system for rapid in vivo analysis of 
human immunodeficiency virus type 1 susceptibility to reverse transcriptase 
inhibitors. Antimicrob Agents Chemother. 1997;41(12):2781-5. 
5. Clarke L, Carbon J. A colony bank containing synthetic Col El hybrid plasmids 
representative of the entire E. coli genome. Cell. 1976;9(1):91-9. 
6. Hogg S. Essential Microbiology. Second edition. ed: Wiley-Blackwell, Chichester, 
West Sussex, United Kingdom, 2013. 
7. Avila-Rios S, Parkin N, Swanstrom R, Paredes R, Shafer R, Ji H, et al. Next-
Generation Sequencing for HIV Drug Resistance Testing: Laboratory, Clinical, and 
Implementation Considerations. Viruses. 2020;12(6).  
8. Ji H, Sandstrom P, Paredes R, Harrigan PR, Brumme CJ, Avila Rios S, et al. Are We 
Ready for NGS HIV Drug Resistance Testing? The Second "Winnipeg Consensus" 
Symposium. Viruses. 2020;12(6). 
9. Stanford NNRTI Resistance Mutation Scores, Database Version 8.4, dated 16 June 
2017. Available at: https://hivdb.stanford.edu/ (last accessed 21 May 2021. 
10. Wensing AM, Calvez V, Ceccherini-Silberstein F, Charpentier C, Günthard HF, 
Paredes R, et al. 2019 update of the drug resistance mutations in HIV-1. Topic Antivir 
Med 2019, 27(3):111-121. 
 


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8. 
APPENDICES 
8.1. 
Appendix 1 – Tables and Listings Titles 
Tables 
Table 
number 
Title 
14.3.9 
Next Generation Sequencing (NGS) and Phenotypic Susceptibility Analysis 
14.3.9.1 
Accountability 
14.3.9.1.1 
Sample Availability 
14.3.9.2 
Summary of NGS and Paired Population-based Genotype Analysis 
14.3.9.2.1 
Summary of Number of Participants with an Amino Acid Change from Reference 
per Residue in the RT Region Among HIV-1 Seroconversions using Next 
Generation Sequencing with Paired Population-Based Genotypes 
14.3.9.2.2 
Summary of Numbers and Combinations of HIV-1 NNRTI Resistance-associated 
Mutations Among HIV-1 Seroconversions using Next Generation Sequencing 
with Paired Population-Based Genotypes 
14.3.9.3 
Phenotypic Susceptibility Analysis  
14.3.9.3.1 
Summary of Phenotypic Susceptibility to Dapivirine and Other NNRTIs by 
Population-based Genotype  
14.3.9.4 
Summary of Population-Based Genotype Analysis (All Seroconversion Data) 
14.3.9.4.1 
Summary of Number of Participants with an Amino Acid Change from Reference 
per Residue in the RT Region Among HIV-1 Seroconversions using Population-
Based Genotyping  
Listings 
Listing 
number 
Title 
16.2.8.20 
Next Generation Sequencing and Phenotypic Data 
16.2.8.20.1 
Next Generation Sequencing: Listing of All Available Data 
16.2.8.20.2 
Next Generation Sequencing: Listing of Detected NNRTI Resistance-associated 
Mutations 
16.2.8.20.3 
Phenotypic Data: Listing of All Available Data 
16.2.8.20.4 
Genotypic Interpretations with Phenotypic Data: Full Listing for HIV-1 
Seroconverters 
 
Note: Table and listing shells are provided in a separate document. 


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8.2. 
Appendix 2 – Stanford Human Immunodeficiency Virus Type 1 
Drug Resistance (Database Version 8.4 Provided by Stanford 
HIVdb) 
Stanford Mutation List NNRTI Version 8.4 (9) 
NNRTI 
A98G, L100I, L100V, K101E, K101H, K101P, K103E, K103H, K103N, K103Q, K103Rb,  
K103S, K103T, V106A, V106M, V108I, E138A, E138K, E138Q, E138G, E138R, V179D, 
V179E, V179F, V179L, V179T, Y181C, Y181F, Y181G, Y181I, Y181S, Y181V, M184I, 
Y188C, Y188F, Y188H, Y188L, G190A, G190C, G190E, G190Q, G190S, G190T, G190V 
(H221Y, P225H, F227C, F227L, M230I, M230L, P236L, K238T, K238N, Y318F, N348I). 
Other 
V90I, A98S, K101N, K101Q, K101R, K103E, K103M, K103Q, K103R, V106I, V108A, 
I132M, I132L, V179A, V179I, V179M, Y181N, (F227Ic, F227R
c, F227V
c, Y232H, L234I
c, 
P236L
c). 
These ‘other’ mutations do not contribute to the Stanford Mutation Score for EFV, ETV, 
NVP or RPV, so they are not included in the NNRTI RAM summary tables. However, they 
are listed among the NNRTI Resistance Notes on the Stanford web page 
(https://hivdb.stanford.edu/dr-summary/resistance-notes/NNRTI/ accessed 24 March 2021), 
the IAS USA 2019 update of drug resistance mutations in HIV-1 (10) or during in vitro 
passage experimentation (Module 2.7.2.4) and will be included in summaries of sequence 
data by codon.  
 
 
b 
K103R, which by itself is polymorphic and non-scoring in the Stanford HIVdb algorithm Version 8.4, 
augments the V179D resistance scores for efavirenz and nevirapine from potential low-level- to 
intermediate resistance. 
c 
These mutations are associated with resistance to doravirine. 


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8.3. 
Appendix 3 – Stanford Non-nucleoside Reverse Transcriptase 
Inhibitor Resistance Mutation Scores (Database Version 8.4, 
dated 18 July 2018) 
Rule 
EFV 
ETR 
NVP 
RPV 
A98G 
15 
10 
30 
15 
L100I 
60 
30 
60 
60 
L100V 
30 
10 
30 
15 
K101E 
15 
15 
30 
45 
K101H 
10 
10 
15 
10 
K101P 
60 
60 
60 
60 
K103H 
60 
0 
60 
0 
K103N 
60 
0 
60 
0 
K103S 
45 
0 
60 
0 
K103T 
15 
0 
60 
0 
V106A 
45 
0 
60 
0 
[V106I]a 
[0] 
[10] 
[10] 
[10] 
V106M 
60 
0 
60 
0 
V108I 
10 
0 
15 
0 
E138A 
0 
10 
0 
15 
E138G 
10 
10 
10 
15 
E138K 
10 
10 
10 
45 
E138Q 
10 
10 
10 
15 
E138R 
10 
10 
10 
15 
V179D 
10 
10 
10 
10 
V179E 
10 
10 
10 
10 
V179F 
10 
15 
15 
15 
V179L 
10 
10 
10 
15 
Y181C 
30 
30 
60 
45 
Y181F 
15 
15 
60 
30 
Y181G 
15 
15 
60 
30 
Y181I 
30 
60 
60 
60 
Y181S 
15 
15 
60 
30 
Y181V 
30 
60 
60 
60 
Y188C 
60 
0 
60 
0 
Y188F 
60 
0 
60 
30 
Y188H 
30 
0 
60 
0 
Y188L 
60 
10 
60 
60 


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Rule 
EFV 
ETR 
NVP 
RPV 
G190A 
45 
10 
60 
15 
G190C 
60 
10 
60 
10 
G190E 
60 
45 
60 
60 
G190Q 
60 
45 
60 
45 
G190S 
60 
10 
60 
15 
G190T 
60 
10 
60 
10 
G190V 
60 
10 
60 
10 
H221Y 
10 
10 
15 
15 
P225H 
45 
0 
45 
0 
F227C 
45 
30 
45 
45 
F227L 
15 
0 
30 
0 
M230I 
15 
15 
30 
30 
M230L 
45 
30 
60 
60 
K238N 
10 
0 
10 
0 
K238T 
30 
0 
30 
0 
Y318F 
10 
0 
30 
0 
N348I 
0 
0 
15 
0 
K101E + Y181C 
5 
5 
5 
0 
K101E + M184I 
0 
0 
0 
15 
K101E + Y188L 
0 
5 
0 
0 
K101E + G190A 
0 
5 
0 
0 
K101E + G190S 
0 
5 
0 
0 
K103R + V179D 
20 
0 
20 
15 
V106A + F227L 
15 
0 
0 
0 
E138K + M184I 
0 
0 
0 
15 
V179F + Y181C 
0 
15 
0 
15 
V179T + Y181C 
0 
10 
0 
10 
Y181C + G190ACSTV 
0 
10 
0 
10 
A98G + Y181C 
5 
5 
5 
 
EFV = efavirenz; ETR = etravirine; NVP = nevirapine; RPV = rilpivirine 
a Scoring is included in the current version of the Stanford HIVdb algorithm (Version 8.9-1; dated 25 October 2019). 
Note: When a participant has multiple mutations, the scores for the individual mutations and for the combination of 
mutations have to be added in order to obtain the total score. 
Example: A participant with mutations K101E and Y181C will have a EFV mutation score of 
15 + 30 + 5 = 50. 
 


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TABLE SHELLS 
 
Table 
Title 
14.3.9 
Next Generation Sequencing (NGS) and Phenotypic Susceptibility Analysis 
14.3.9.1 
Accountability 
14.3.9.1.1 
Sample Availability 
14.3.9.2 
Summary of NGS and Paired Population-based Genotype Analysis 
14.3.9.2.1 
Summary of Number of Participants with an Amino Acid Change from 
Reference per Residue in the NGS Sequenced RT Region Among HIV-1 
Seroconversions using Next Generation Sequencing with Paired Population-
Based Genotypes 
14.3.9.2.2 
Summary of Numbers and Combinations of HIV-1 NNRTI Resistance-
associated Mutations Among HIV-1 Seroconverters using Next Generation 
Sequencing with Paired Population-Based Genotypes 
14.3.9.3 
Phenotypic Susceptibility Analysis 
14.3.9.3.1 
Summary of Phenotypic Susceptibility to Dapivirine and Other NNRTIs by 
Population-based Genotype 
14.3.9.4 
Summary of All Seroconversion Population-Based Genotyping 
14.3.9.4.1 
Summary of Number of Participants with an Amino Acid Change from 
Reference per Residue in the RT Region Among HIV-1 Seroconversions using 
Population-Based Genotyping (All Seroconversion Data) 
 
 


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Table 14.3.9.1.1 
Sample Availability 
Virology Population 
 
  
Statistic 
HIV-1 Seroconversion Participants, N1 
XX 
Seroconversion Samples Available, N2 (%) (a) 
xx (x.x%) 
 
No sample n (%) (a) 
xx (x.x%) 
 
Sample not suitable n (%) (a) 
xx (x.x%) 
 
No consent n (%) (a) 
xx (x.x%) 
Seroconversion Samples with NGS Analysis Attempted, n (%) (b) 
xx (x.x%) 
HIV-1 seroconversion participants with a successful NGS genotype, N3 (%) (b) 
xx (x.x%) 
Sensitivity to detect RAMs present with at least: 
≤ 1% variant, n (%) (c) 
xx (x.x%) 
> 1% to 5% variant, n (%) (c) 
xx (x.x%) 
> 5% to 10% variant, n (%) (c) 
xx (x.x%) 
Invalid Result, n (%) (b, d) 
xx (x.x%) 
Test performed, no output (c) 
xx (x.x%) 
Sensitivity to detect RAMs present at: 
>10% to 20% variant, n (%) (c,d) 
xx (x.x%) 
> 20% variant, n (%) (c,d) 
xx (x.x%) 
Seroconversion Samples with Phenotypic Susceptibility Analysis Attempted, n (%) (b) 
xx (x.x%) 
HIV-1 seroconversion participants with any successful Phenotypic analysis (%) (b, e) 
xx (x.x%) 
Invalid or No Test Result, n (%) (b) 
xx (x.x%) 
Failed Testing (All phenotypes), n (%) (b) 
xx (x.x%) 
No test (Insufficient sample volume), n (%) (b,f) 
xx (x.x%) 


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The percentage calculation is based on the total number of participants in the denoted section. 
(a) Denominator = N1. (b) Denominator = N2. (c) Denominator = N3. 
(d) Due to low UMI (< 28), these are considered to provide invalid results. Mutations detected in these samples will be reported separately. 
(e) In the unlikely event of one to four of the five phenotypic test results for successful analysis being missing, this should be footnoted with the affected participant 
identifier.  
(f) Some samples may have had inadequate volume to perform both the NGS and the phenotypic tests and so analysis was performed with NGS as priority, followed by 
phenotype determination. 
 
 
 


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Table 14.3.9.2.1 
Summary of Numbers of Participants with an Amino Acid Change from Reference per Residue in the NGS Sequenced RT Region Among HIV-1 
Seroconverters using Next Generation Sequencing with Paired Population-Based Genotyping 
Virology Population 
 
Next Generation Sequencing: Number of Participants with an Amino Acid Change from Reference per Residue in the RT Region Among HIV-1 Seroconverters 
 
Statistic 
Sensitivity Level 1% 
Participants with a Next Generation Sequencing Assessment (1% sensitivity: UMI >/= 298) at  
      seroconversion time point (N) 
XX 
Amino Acid Change in RT (a) 
NGS 
n (%) 
Paired Population-based 
Genotype 
n (%) 
Y82X 
X (XX.X%) 
X (XX.X%) 
Y87X 
X (XX.X%) 
X (XX.X%) 
Y88X 
X (XX.X%) 
X (XX.X%) 
Y88X + Y88Z  or Y88X/Z 
X (XX.X%) 
X (XX.X%) 
Y90X 
X (XX.X%) 
X (XX.X%) 
etc. 
Sensitivity Level 5% 
Participants with a Next Generation Sequencing Assessment (5% sensitivity: UMI >/= 58) at  
      seroconversion time point (N) 
XX 
Amino Acid Change in RT (a) 
NGS 
n (%) 
Paired Population-based 
Genotype 
n (%) 
Y82X 
X (XX.X%) 
X (XX.X%) 
Y87X 
X (XX.X%) 
X (XX.X%) 
Y88X 
X (XX.X%) 
X (XX.X%) 


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Y88X + Y88Z  or Y88X/Z 
X (XX.X%) 
X (XX.X%) 
Y90X 
X (XX.X%) 
X (XX.X%) 
etc. 
Sensitivity Level 10% 
Participants with a Next Generation Sequencing Assessment (10% sensitivity: UMI >/= 28) at  
      seroconversion time point (N) 
XX 
Amino Acid Change in RT (a) 
NGS  
n (%) 
Paired Population-based 
Genotype  
n (%) 
Y82X 
X (XX.X%) 
X (XX.X%) 
Y87X 
X (XX.X%) 
X (XX.X%) 
Y88X 
X (XX.X%) 
X (XX.X%) 
Y88X + Y88Z  or Y88X/Z 
X (XX.X%) 
X (XX.X%) 
Y90X 
X (XX.X%) 
X (XX.X%) 
etc. 
Sensitivity Level > 10%  
Participants with a Next Generation Sequencing Assessment (> 10% sensitivity: UMI < 28) at  
      seroconversion time point (N). 
XX 
Amino Acid Change in RT (a) 
NGS  
n (%) (a) 
Paired Population-based 
Genotype 
n (%) 
Y82X 
X (XX.X%) 
X (XX.X%) 
Y87X 
X (XX.X%) 
X (XX.X%) 
Y88X 
X (XX.X%) 
X (XX.X%) 
Y88Z 
X (XX.X%) 
X (XX.X%) 
Y88X + Y88Z or Y88X/Z 
X (XX.X%) 
X (XX.X%) 
Y90X 
X (XX.X%) 
X (XX.X%) 


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etc. 
N = Number of participants with data; n = number of participants with that observation.  
NGS analyses should be considered exploratory. 
The percentage calculation is based on the total number of participants with a next-generation sequencing assessment.  
The sequenced region contains RT amino acids 80 – 150 and 152 - 212.  
Participants may be counted more than once. 
The reference sequence was the HXB2 sequence (NCBI accession number K03455.1, https://www.ncbi.nlm.nih.gov/nuccore/1906382 accessed 13th January 2021). Within 
the NGS sequencing range, this differs from the Stanford consensus B sequence only at residue 122 (consensus amino acid: lysine, 'K'; HXB2: glutamic acid, 'E').  
(a) Mixtures of variants with wild-type and mutant viral species (e.g. K103N at ≤ 99% prevalence) for NGS data will be counted as the mutation being present (i.e. as 
‘K103N’). Similar mixtures detected using population-based genotyping (e.g. K103K/N) should be reported and counted as such. For NGS data, each mutant viral species 
will be counted (e.g. K103N and K103S from the same sample are counted in separate rows). Population-based genotypes having mixtures of mutations (e.g. K103N/S), 
will be reported as such and counted only once. Codons will be counted separately, therefore one participant with multiple mutations (e.g. K103N, E138A) will be counted 
more than once (i.e. twice in the example given). 
 
[Note to programmer: Amino acids are listed in numeric order; population-based genotyping data is included as numbers are different from main analysis; residues with 
only null entries should be omitted; more than one variant at any residue should be reported separately; mixtures in the population-based genotypes should be counted if the 
mutation is present in the mixture (e.g. V108V/I would be counted with V108I in the NGS row). A separate line showing the mixture in the population-based genotype 
column only should then be included – mixtures will not be present by NGS. See above for Sensitivity > 10%] 
 
 
 


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Table 14.3.9.2.2 
Summary of Numbers and Combinations of HIV-1 NNRTI Resistance-associated Mutations Among HIV-1 Seroconverters using Next Generation 
Sequencing with Paired Population-Based Genotyping 
Virology Population 
 
 
Statistic 
Sensitivity Level 1% 
Participants with a Next Generation Sequencing Assessment (1% sensitivity: UMI >/= 298) at 
seroconversion time point (N) 
XX 
NGS 
n (%) 
Population-based Genotype 
n (%) 
Stanford Number of NNRTI RAMs per participant (a) 
None 
XX (X.X%) 
XX (X.X%) 
Any 
X (X.X%) 
X (X.X%) 
One 
X (X.X%) 
X (X.X%) 
Two  
X (X.X%) 
X (X.X%) 
Three or more 
X (X.X%) 
X (X.X%) 
Average 
0.XX 
0.XX 
Stanford NNRTI resistance mutation combinations (a) 
A98G 
X (X.X%) 
X (X.X%) 
K101E 
X (X.X%) 
X (X.X%) 
K101E + E138A 
X (X.X%) 
X (X.X%) 
K101E + E138A + E138K (or K101E + E138A/K (b)) 
X (X.X%) 
X (X.X%) 
etc. 
 
 
Sensitivity Level 5% 
Participants with a Next Generation Sequencing Assessment (5% sensitivity: UMI >/= 58) at 
seroconversion time point (N) 
XX 


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NGS n (%) 
Population-based Genotype 
n (%) 
Stanford Number of NNRTI RAMs per participant (a) 
None 
XX (X.X%) 
XX (X.X%) 
Any 
X (X.X%) 
X (X.X%) 
One 
X (X.X%) 
X (X.X%) 
Two  
X (X.X%) 
X (X.X%) 
Three or more 
X (X.X%) 
X (X.X%) 
Average 
0.XX 
0.XX 
Stanford NNRTI resistance mutation combinations (a) 
A98G 
X (X.X%) 
X (X.X%) 
K101E 
X (X.X%) 
X (X.X%) 
K101E + E138A 
X (X.X%) 
X (X.X%) 
K101E + E138A + E138K (or K101E + E138A/K (b)) 
X (X.X%) 
X (X.X%) 
etc. 
 
 
 
 
 


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Sensitivity Level 10% 
Participants with a Next Generation Sequencing Assessment (10% sensitivity: UMI >/= 28) at 
seroconversion time point (N) 
XX 
NGS 
n (%) 
Population-based Genotype 
n (%)  
Stanford Number of NNRTI RAMs per participant (a) 
None 
XX (X.X%) 
XX (X.X%) 
Any 
X (X.X%) 
X (X.X%) 
One 
X (X.X%) 
X (X.X%) 
Two  
X (X.X%) 
X (X.X%) 
Three or more 
X (X.X%) 
X (X.X%) 
Average 
0.XX 
0.XX 
Stanford NNRTI resistance mutation combinations (a) 
A98G 
X (X.X%) 
X (X.X%) 
K101E 
X (X.X%) 
X (X.X%) 
K101E + E138A 
X (X.X%) 
X (X.X%) 
K101E + E138A + E138K (or K101E + E138A/K (b)) 
X (X.X%) 
X (X.X%) 
etc. as above 
 
 
 


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Sensitivity Level > 10% 
Participants with a Next Generation Sequencing Assessment (> 10% sensitivity: UMI < 28) at 
seroconversion time point (N) 
XX 
NGS 
n (%) 
Population-based Genotype 
n (%) 
Stanford Number of NNRTI RAMs per participant (a) 
None 
XX (X.X%) 
XX (X.X%) 
Any 
X (X.X%) 
X (X.X%) 
One 
X (X.X%) 
X (X.X%) 
Two  
X (X.X%) 
X (X.X%) 
Three or more 
X (X.X%) 
X (X.X%) 
Average 
0.XX 
0.XX 
Stanford NNRTI RAM combinations  (a) 
A98G 
X (X.X%) 
X (X.X%) 
K101E 
X (X.X%) 
X (X.X%) 
K101E + E138A 
X (X.X%) 
X (X.X%) 
K101E + E138A + E138K (or K101E + E138A/K (b)) 
X (X.X%) 
X (X.X%) 
etc. as above 
N = Number of participants with data; n = number of participants with that observation; N/A = not applicable (mutations pattern was not detected); NNRTI = Non-
nucleoside Reverse Transcriptase Inhibitor.  
The percentage calculation is based on the total number of participants in the Virology Population and with a qualifying NGS assessment.  
Participants are counted only once for each analysis (i.e. number of NNRTI RAMs per participant and number of each NNRTI RAM combination) within each sensitivity 
level. 
The sequenced region contains RT amino acids 80 – 150 and 152 - 212. NGS analyses should be considered exploratory. 
The Stanford HIV-1 Drug Resistance Database version 8.4 (dated 2017-06-16) was used.  
(a) Mixtures of variants with wild-type and mutant viral minority species (e.g. K103N at ≤ 99% prevalence for NGS data or K103K/N for population-based genotyping) 
will be counted as the mutation being present (i.e. as ‘K103N’ in this example). Each sequence will be counted only once. 
(b) Mixtures observed using population-based genotyping will be reported as ‘E138A/K’, whereas these will be reported separately as ‘E138A’ and ‘E138K’ using NGS. 


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Table and Listing Shells, Version 1.0 
Version Dated: 24 May 2021 
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[Note to programmer: Amino acids are listed in numeric order; population-based genotyping included as numbers might be different from main analysis. To simplify the 
analysis of population-based genotype mixtures, include the count if the mixture includes a variant from the NGS analysis. Also, if there is more than one variant detected 
by NGS, these should be included in the listed row. The example: K101E + E138A + E138K + Y181C might be represented in the population-based genotype as K101E + 
E138A/K + Y181C the E138A + E138K would count as one mutation, but subsequently broken down by sequence. The example shows all possible population-based 
genotypes, only ones that apply should be included.] 
 
 
 


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Table 14.3.9.3.1 
Summary of Phenotypic Susceptibility to Dapivirine and Other NNRTIs by Population-based Genotype 
Virology Population 
 
All Viruses 
Dapivirine 
Efavirenz  
Etravirine   
Nevirapine   
Rilpivirine   
N 
XX 
XX 
XX 
XX 
XX 
IC50 (nM) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Fold change (a) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Wild-type viruses (b) 
N 
XX 
XX 
XX 
XX 
XX 
IC50 (nM) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
 
Fold change (a) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 


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Viruses with any NNRTI RAM 
N 
XX 
XX 
XX 
XX 
XX 
IC50 (nM) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Fold change (a) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Viruses with one NNRTI RAM 
N 
XX 
XX 
XX 
XX 
XX 
IC50 (nM) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Fold change (a) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Viruses with two NNRTI RAMs 
N 
XX 
XX 
XX 
XX 
XX 
IC50 (nM) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 


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(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Fold change (a) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Viruses with three or more NNRTI RAMs 
N 
XX 
XX 
XX 
XX 
XX 
IC50 (nM) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Fold change (a) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Viruses with A98G 
etc. 
Viruses with K101E 
etc. 
Viruses with K101E + E138A 
etc. 
(a) Fold change = IC50/IC50wild-type reference control. 
(b) Mutations are included from population-based genotyping results (minority species mutations are less likely to influence phenotypes). 
 
 
 


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Table 14.3.9.4.1 
Summary of Number of Participants with an Amino Acid Change from Reference per Residue in the RT Region Among HIV-1 Seroconversions 
using Population-Based Genotyping (All Seroconversion ± 14-Days Data) 
Virology Population 
 
 
Population-based Genotype 
n (%) 
Participants with a population-based genotyping assessment at seroconversion time point (N) 
XX 
Stanford Number of NNRTI RAMs per participant (a) 
None 
XX (X.X%) 
Any 
X (X.X%) 
One 
X (X.X%) 
Two  
X (X.X%) 
Three or more 
X (X.X%) 
Average 
0.XX 
Stanford NNRTI resistance mutation combinations (b) 
A98G 
X (X.X%) 
K101E 
X (X.X%) 
K101E + E138A 
X (X.X%) 
K101E + E138A/K + Y181C 
X (X.X%) 
etc. 
N = Number of participants with data; n = number of participants with that observation; NNRTI = Non-nucleoside Reverse Transcriptase Inhibitor.  
The percentage calculation is based on the total number of participants with a successful population-based genotyping assessment at seroconversion.  
The Stanford HIV-1 Drug Resistance Database version 8.4 (dated 2017-06-16) was used.  
(a) Instances of mixtures among the population-based genotypes that include one or more NNRTI RAM, are counted as if the mutation with the greatest drug resistance 
score was present. 


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LISTING SHELLS 
 
Listing 
Title 
16.2.8.20 
Next Generation Sequencing and Phenotype Susceptibility Data 
16.2.8.20.1 
Next Generation Sequencing: Listing of All Available Data 
16.2.8.20.2 
Next Generation Sequencing: Listing of Detected NNRTI Resistance-associated 
Mutations 
16.2.8.20.4 
Phenotypic Data: Listing of All Available Data 
16.2.8.20.5 
Genotypic Interpretations with Phenotypic Data: Full Listing for HIV-1 
Seroconverters 
Note: Population-based genotyping data are listed in the IPM 032 CSR Listings. 
 


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Listing 16.2.8.20.1 
Next Generation Sequencing: Listing of All Available Data 
Safety Population 
 
PID (a) 
Sample Date 
Days (b) Days (c) 
Visit Day 
(d) 
Log10 HIV-1 
RNA 
(copies/mL) 
Number  
UMI with 
Consensus 
Sample 
Sensitivity 
(%) 
Valid Result 
Amino acid (% UMI) Change from 
Reference (e) 
XXX-XXXXXX 
DDMMMYYYY XX 
XX 
XXX 
X.XXX 
XXXX 
X 
Yes/No 
YxxX (xx), YxxX (xx), YxxxX 
(xx),…. 
etc. 
(a) PIDs infected on enrolment indicated with 'α'; PIDs with seroconversion off DVR-004 use indicated with 'β'. 
(b) Days since seroconversion (negative values indicate evaluation prior to seroconversion). 
(c) Days since first HIV-1 RNA detection. 
(d) Visits indicated with a * are not within 14 days of the seroconversion time point. 
(e) Reference sequence: HXB2 (accession number K03455-1).  
The sequenced region contains RT amino acids 81 – 150, 152 - 212. NGS analyses are considered exploratory. 
[Notes to programmer: Amino acids are listed in numeric order (Note e); choose appropriate markers for different populations (Note a).] 
 
 
 
 
 


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Listing 16.2.8.20.2 
Next Generation Sequencing: Listing of Detected NNRTI Resistance-associated Mutations 
Safety Population 
 
PID (a) 
Sample Date 
Days (b)  
Days (c)  
Visit Day  
Visit (d) 
Number 
UMI with 
Consensus 
Sample 
Sensitivity 
(%) 
Number 
of 
Mutations 
NNRTI RAMs (e) 
XXX-
XXXXXX 
DDMMMYYYY 
XX 
XX 
XXX 
Month 
XX/ 
Week XX 
XXXX 
X 
X 
YxxZ (xx), YxxZ (xx),…. 
XXX-
XXXXXX 
DDMMMYYYY 
XX 
XX 
XXX 
Month 
XX/ 
Week XX 
XXXX 
X 
X 
None 
XXX-
XXXXXX 
DDMMMYYYY 
XX 
XX 
XXX 
Month 
XX/ 
Week XX 
XXXX 
X 
X 
No Test 
etc. 
Table includes PIDS only if NNRTI RAMs were detected in NGS analysis. 
(a) PIDs infected on enrolment indicated with 'α'; PIDs with seroconversion off DVR-004 use indicated with 'β'.  
(b) Days since seroconversion (negative values indicate evaluation prior to seroconversion). 
(c) Days since first HIV-1 RNA detection. 
(d) Visits indicated with a * are not within 14 days of the seroconversion time point. 
(e) Mutations reported according to Stanford HIVdb algorithm version 8.4 (see SAP). 
The sequenced region contains RT amino acids 81 – 150, 152 - 212. NGS analyses should be considered exploratory. 
[Notes to programmer: Amino acids are listed in numeric order (Note e); choose appropriate markers for different populations (Note a).] 
 
 
 


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Listing 16.2.8.20.4 
Phenotypic Data: Listing of All Available Data 
Safety Population 
 
DPV 
EFV 
ETR 
NVP 
RPV 
PID 
Sample Date 
NNRTI 
RAMs 
Result 
ID 
IC50 
(nM) 
FC (a) 
 
IC50 
(nM) 
FC (a) 
 
IC50 
(nM) 
FC (a) 
 
IC50 
(nM) 
FC (a) 
 
IC50 
(nM) 
FC (a) 
XXX-
XXXXXX 
DDMMMYYYY 
None 
1 
x.xx 
(x.xx) 
 
x.xx 
(x.xx) 
 
x.xx 
(x.xx) 
 
x.xx 
(x.xx) 
 
x.xx 
(x.xx) 
2 
x.xx 
(x.xx) 
 
 
 
 
3 
x.xx 
(x.xx) 
 
 
 
 
Avg 
x.xx 
(x.xx) 
x.x 
 
x.xx 
(x.xx) 
x.x 
 
x.xx 
(x.xx) 
x.x 
 
x.xx 
(x.xx) 
x.x 
 
x.xx 
(x.xx) 
x.x 
etc. 
 
 
 
 
 
 
 
 
DPV = Dapivirine; EFV = Efavirenz; ETR = Etravirine; FC: Fold change; IC50: 50% Inhibitory concentration; NNRTI: Non-nucleoside reverse transcriptase inhibitor; NVP 
= Nevirapine; PID: Participant identifier; RAM: Resistance-associated mutation; RPV = Rilpivirine 
(a) FC = IC50/IC50CONTROL (Control IC50 [nM] range: DPV: n = X:  X.XX - X.XX; EFV: n = X:  X.XX - X.XX ; ETR: n = X:  X.XX - X.XX; NVP: n = X:  X.XX - 
X.XX; RPV: n = X:  X.XX - X.XX). n: number of runs to complete the analysis. 
(b) IC50 sample and (IC50 reference virus) are given.  
[Note to programmer: Order by PID and then by NNRTI RAMs with 'None' first, then mutations in numeric order. Note the reference virus will be different from that in 
IPM 027 - a single lab-strain has been used per run.] 
 
 
 


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Listing 16.2.8.20.5 
Genotypic Interpretations with Phenotypic Data: Full Listing for HIV-1 Seroconverters 
Safety Population 
 
NNRTI RAMs 
NNRTI Genotypic 
Susceptibility 
(Population-based sequencing) 
(a) 
Phenotype 
PID 
Sample Date 
Population 
NGS 
NNRTI 
IC50 (nM) 
FC (b) 
XXX-XXXXXX 
DDMMMYYYY 
None 
None 
Dapivirine 
N/A 
X.XX 
X.X 
Efavirenz 
XX (YYY) 
X.XX 
X.X 
Etravirine 
XX (YYY) 
X.XX 
X.X 
Nevirapine 
XX (YYY) 
X.XX 
X.X 
Rilpivirine 
XX (YYY) 
X.XX 
X.X 
XXX-XXXXXX 
DDMMMYYYY 
YXXY 
YXXY 
Dapivirine 
N/A 
X.XX 
X.X 
Efavirenz 
XX (YYY) 
X.XX 
X.X 
Etravirine 
XX (YYY) 
X.XX 
X.X 
Nevirapine 
XX (YYY) 
X.XX 
X.X 
Rilpivirine 
XX (YYY) 
X.XX 
X.X 
etc. 
HLR = High-level resistant; Interm = Intermediate resistant; LLR = Low-level resistant; N/A = Not applicable; NNRTI = Non-nucleoside Reverse Transcriptase Inhibitor; 
PLLR = Potential low-level resistant; RAM: Resistance-associated mutation; Sus = Susceptibility. 
(a) Stanford HIVdb algorithm version 8.4 drug resistance score (interpretation: Sus, PLLR, LLR, Interm, HLR). 
(b) FC = IC50/IC50Control (Control IC50 [nM] range: DPV: n = X:  X.XX - X.XX; EFV: n = X:  X.XX - X.XX ; ETR: n = X:  X.XX - X.XX; NVP: n = X:  X.XX - X.XX; 
RPV: n = X:  X.XX - X.XX)  
[Note to programmer: Order by PID then by NNRTI RAMs with 'None' first, then mutations in numeric order (as per Phenotype Listing 16.2.8.20.4).] 
 


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IPM 032 Virology Addendum SAP 
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IPM 032 VIROLOGY ADDENDUM SAP 
APPENDIX 1 
TABLE AND LISTING SHELLS – VERSION 1.0, 24 MAY 2021 


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TABLE SHELLS 
 
Table 
Title 
14.3.9 
Next Generation Sequencing (NGS) and Phenotypic Susceptibility Analysis 
14.3.9.1 
Accountability 
14.3.9.1.1 
Sample Availability 
14.3.9.2 
Summary of NGS and Paired Population-based Genotype Analysis 
14.3.9.2.1 
Summary of Number of Participants with an Amino Acid Change from 
Reference per Residue in the NGS Sequenced RT Region Among HIV-1 
Seroconversions using Next Generation Sequencing with Paired Population-
Based Genotypes 
14.3.9.2.2 
Summary of Numbers and Combinations of HIV-1 NNRTI Resistance-
associated Mutations Among HIV-1 Seroconverters using Next Generation 
Sequencing with Paired Population-Based Genotypes 
14.3.9.3 
Phenotypic Susceptibility Analysis 
14.3.9.3.1 
Summary of Phenotypic Susceptibility to Dapivirine and Other NNRTIs by 
Population-based Genotype 
14.3.9.4 
Summary of All Seroconversion Population-Based Genotyping 
14.3.9.4.1 
Summary of Number of Participants with an Amino Acid Change from 
Reference per Residue in the RT Region Among HIV-1 Seroconversions using 
Population-Based Genotyping (All Seroconversion Data) 
 
 


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Table 14.3.9.1.1 
Sample Availability 
Virology Population 
 
  
Statistic 
HIV-1 Seroconversion Participants, N1 
XX 
Seroconversion Samples Available, N2 (%) (a) 
xx (x.x%) 
 
No sample n (%) (a) 
xx (x.x%) 
 
Sample not suitable n (%) (a) 
xx (x.x%) 
 
No consent n (%) (a) 
xx (x.x%) 
Seroconversion Samples with NGS Analysis Attempted, n (%) (b) 
xx (x.x%) 
HIV-1 seroconversion participants with a successful NGS genotype, N3 (%) (b) 
xx (x.x%) 
Sensitivity to detect RAMs present with at least: 
≤ 1% variant, n (%) (c) 
xx (x.x%) 
> 1% to 5% variant, n (%) (c) 
xx (x.x%) 
> 5% to 10% variant, n (%) (c) 
xx (x.x%) 
Invalid Result, n (%) (b, d) 
xx (x.x%) 
Test performed, no output (c) 
xx (x.x%) 
Sensitivity to detect RAMs present at: 
>10% to 20% variant, n (%) (c,d) 
xx (x.x%) 
> 20% variant, n (%) (c,d) 
xx (x.x%) 
Seroconversion Samples with Phenotypic Susceptibility Analysis Attempted, n (%) (b) 
xx (x.x%) 
HIV-1 seroconversion participants with any successful Phenotypic analysis (%) (b, e) 
xx (x.x%) 
Invalid or No Test Result, n (%) (b) 
xx (x.x%) 
Failed Testing (All phenotypes), n (%) (b) 
xx (x.x%) 
No test (Insufficient sample volume), n (%) (b,f) 
xx (x.x%) 


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The percentage calculation is based on the total number of participants in the denoted section. 
(a) Denominator = N1. (b) Denominator = N2. (c) Denominator = N3. 
(d) Due to low UMI (< 28), these are considered to provide invalid results. Mutations detected in these samples will be reported separately. 
(e) In the unlikely event of one to four of the five phenotypic test results for successful analysis being missing, this should be footnoted with the affected participant 
identifier.  
(f) Some samples may have had inadequate volume to perform both the NGS and the phenotypic tests and so analysis was performed with NGS as priority, followed by 
phenotype determination. 
 
 
 


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Table 14.3.9.2.1 
Summary of Numbers of Participants with an Amino Acid Change from Reference per Residue in the NGS Sequenced RT Region Among HIV-1 
Seroconverters using Next Generation Sequencing with Paired Population-Based Genotyping 
Virology Population 
 
Next Generation Sequencing: Number of Participants with an Amino Acid Change from Reference per Residue in the RT Region Among HIV-1 Seroconverters 
 
Statistic 
Sensitivity Level 1% 
Participants with a Next Generation Sequencing Assessment (1% sensitivity: UMI >/= 298) at  
      seroconversion time point (N) 
XX 
Amino Acid Change in RT (a) 
NGS 
n (%) 
Paired Population-based 
Genotype 
n (%) 
Y82X 
X (XX.X%) 
X (XX.X%) 
Y87X 
X (XX.X%) 
X (XX.X%) 
Y88X 
X (XX.X%) 
X (XX.X%) 
Y88X + Y88Z  or Y88X/Z 
X (XX.X%) 
X (XX.X%) 
Y90X 
X (XX.X%) 
X (XX.X%) 
etc. 
Sensitivity Level 5% 
Participants with a Next Generation Sequencing Assessment (5% sensitivity: UMI >/= 58) at  
      seroconversion time point (N) 
XX 
Amino Acid Change in RT (a) 
NGS 
n (%) 
Paired Population-based 
Genotype 
n (%) 
Y82X 
X (XX.X%) 
X (XX.X%) 
Y87X 
X (XX.X%) 
X (XX.X%) 
Y88X 
X (XX.X%) 
X (XX.X%) 


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Y88X + Y88Z  or Y88X/Z 
X (XX.X%) 
X (XX.X%) 
Y90X 
X (XX.X%) 
X (XX.X%) 
etc. 
Sensitivity Level 10% 
Participants with a Next Generation Sequencing Assessment (10% sensitivity: UMI >/= 28) at  
      seroconversion time point (N) 
XX 
Amino Acid Change in RT (a) 
NGS  
n (%) 
Paired Population-based 
Genotype  
n (%) 
Y82X 
X (XX.X%) 
X (XX.X%) 
Y87X 
X (XX.X%) 
X (XX.X%) 
Y88X 
X (XX.X%) 
X (XX.X%) 
Y88X + Y88Z  or Y88X/Z 
X (XX.X%) 
X (XX.X%) 
Y90X 
X (XX.X%) 
X (XX.X%) 
etc. 
Sensitivity Level > 10%  
Participants with a Next Generation Sequencing Assessment (> 10% sensitivity: UMI < 28) at  
      seroconversion time point (N). 
XX 
Amino Acid Change in RT (a) 
NGS  
n (%) (a) 
Paired Population-based 
Genotype 
n (%) 
Y82X 
X (XX.X%) 
X (XX.X%) 
Y87X 
X (XX.X%) 
X (XX.X%) 
Y88X 
X (XX.X%) 
X (XX.X%) 
Y88Z 
X (XX.X%) 
X (XX.X%) 
Y88X + Y88Z or Y88X/Z 
X (XX.X%) 
X (XX.X%) 
Y90X 
X (XX.X%) 
X (XX.X%) 


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etc. 
N = Number of participants with data; n = number of participants with that observation.  
NGS analyses should be considered exploratory. 
The percentage calculation is based on the total number of participants with a next-generation sequencing assessment.  
The sequenced region contains RT amino acids 80 – 150 and 152 - 212.  
Participants may be counted more than once. 
The reference sequence was the HXB2 sequence (NCBI accession number K03455.1, https://www.ncbi.nlm.nih.gov/nuccore/1906382 accessed 13th January 2021). Within 
the NGS sequencing range, this differs from the Stanford consensus B sequence only at residue 122 (consensus amino acid: lysine, 'K'; HXB2: glutamic acid, 'E').  
(a) Mixtures of variants with wild-type and mutant viral species (e.g. K103N at ≤ 99% prevalence) for NGS data will be counted as the mutation being present (i.e. as 
‘K103N’). Similar mixtures detected using population-based genotyping (e.g. K103K/N) should be reported and counted as such. For NGS data, each mutant viral species 
will be counted (e.g. K103N and K103S from the same sample are counted in separate rows). Population-based genotypes having mixtures of mutations (e.g. K103N/S), 
will be reported as such and counted only once. Codons will be counted separately, therefore one participant with multiple mutations (e.g. K103N, E138A) will be counted 
more than once (i.e. twice in the example given). 
 
[Note to programmer: Amino acids are listed in numeric order; population-based genotyping data is included as numbers are different from main analysis; residues with 
only null entries should be omitted; more than one variant at any residue should be reported separately; mixtures in the population-based genotypes should be counted if the 
mutation is present in the mixture (e.g. V108V/I would be counted with V108I in the NGS row). A separate line showing the mixture in the population-based genotype 
column only should then be included – mixtures will not be present by NGS. See above for Sensitivity > 10%] 
 
 
 


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Table 14.3.9.2.2 
Summary of Numbers and Combinations of HIV-1 NNRTI Resistance-associated Mutations Among HIV-1 Seroconverters using Next Generation 
Sequencing with Paired Population-Based Genotyping 
Virology Population 
 
 
Statistic 
Sensitivity Level 1% 
Participants with a Next Generation Sequencing Assessment (1% sensitivity: UMI >/= 298) at 
seroconversion time point (N) 
XX 
NGS 
n (%) 
Population-based Genotype 
n (%) 
Stanford Number of NNRTI RAMs per participant (a) 
None 
XX (X.X%) 
XX (X.X%) 
Any 
X (X.X%) 
X (X.X%) 
One 
X (X.X%) 
X (X.X%) 
Two  
X (X.X%) 
X (X.X%) 
Three or more 
X (X.X%) 
X (X.X%) 
Average 
0.XX 
0.XX 
Stanford NNRTI resistance mutation combinations (a) 
A98G 
X (X.X%) 
X (X.X%) 
K101E 
X (X.X%) 
X (X.X%) 
K101E + E138A 
X (X.X%) 
X (X.X%) 
K101E + E138A + E138K (or K101E + E138A/K (b)) 
X (X.X%) 
X (X.X%) 
etc. 
 
 
Sensitivity Level 5% 
Participants with a Next Generation Sequencing Assessment (5% sensitivity: UMI >/= 58) at 
seroconversion time point (N) 
XX 


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NGS n (%) 
Population-based Genotype 
n (%) 
Stanford Number of NNRTI RAMs per participant (a) 
None 
XX (X.X%) 
XX (X.X%) 
Any 
X (X.X%) 
X (X.X%) 
One 
X (X.X%) 
X (X.X%) 
Two  
X (X.X%) 
X (X.X%) 
Three or more 
X (X.X%) 
X (X.X%) 
Average 
0.XX 
0.XX 
Stanford NNRTI resistance mutation combinations (a) 
A98G 
X (X.X%) 
X (X.X%) 
K101E 
X (X.X%) 
X (X.X%) 
K101E + E138A 
X (X.X%) 
X (X.X%) 
K101E + E138A + E138K (or K101E + E138A/K (b)) 
X (X.X%) 
X (X.X%) 
etc. 
 
 
 
 
 


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Sensitivity Level 10% 
Participants with a Next Generation Sequencing Assessment (10% sensitivity: UMI >/= 28) at 
seroconversion time point (N) 
XX 
NGS 
n (%) 
Population-based Genotype 
n (%)  
Stanford Number of NNRTI RAMs per participant (a) 
None 
XX (X.X%) 
XX (X.X%) 
Any 
X (X.X%) 
X (X.X%) 
One 
X (X.X%) 
X (X.X%) 
Two  
X (X.X%) 
X (X.X%) 
Three or more 
X (X.X%) 
X (X.X%) 
Average 
0.XX 
0.XX 
Stanford NNRTI resistance mutation combinations (a) 
A98G 
X (X.X%) 
X (X.X%) 
K101E 
X (X.X%) 
X (X.X%) 
K101E + E138A 
X (X.X%) 
X (X.X%) 
K101E + E138A + E138K (or K101E + E138A/K (b)) 
X (X.X%) 
X (X.X%) 
etc. as above 
 
 
 


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Sensitivity Level > 10% 
Participants with a Next Generation Sequencing Assessment (> 10% sensitivity: UMI < 28) at 
seroconversion time point (N) 
XX 
NGS 
n (%) 
Population-based Genotype 
n (%) 
Stanford Number of NNRTI RAMs per participant (a) 
None 
XX (X.X%) 
XX (X.X%) 
Any 
X (X.X%) 
X (X.X%) 
One 
X (X.X%) 
X (X.X%) 
Two  
X (X.X%) 
X (X.X%) 
Three or more 
X (X.X%) 
X (X.X%) 
Average 
0.XX 
0.XX 
Stanford NNRTI RAM combinations  (a) 
A98G 
X (X.X%) 
X (X.X%) 
K101E 
X (X.X%) 
X (X.X%) 
K101E + E138A 
X (X.X%) 
X (X.X%) 
K101E + E138A + E138K (or K101E + E138A/K (b)) 
X (X.X%) 
X (X.X%) 
etc. as above 
N = Number of participants with data; n = number of participants with that observation; N/A = not applicable (mutations pattern was not detected); NNRTI = Non-
nucleoside Reverse Transcriptase Inhibitor.  
The percentage calculation is based on the total number of participants in the Virology Population and with a qualifying NGS assessment.  
Participants are counted only once for each analysis (i.e. number of NNRTI RAMs per participant and number of each NNRTI RAM combination) within each sensitivity 
level. 
The sequenced region contains RT amino acids 80 – 150 and 152 - 212. NGS analyses should be considered exploratory. 
The Stanford HIV-1 Drug Resistance Database version 8.4 (dated 2017-06-16) was used.  
(a) Mixtures of variants with wild-type and mutant viral minority species (e.g. K103N at ≤ 99% prevalence for NGS data or K103K/N for population-based genotyping) 
will be counted as the mutation being present (i.e. as ‘K103N’ in this example). Each sequence will be counted only once. 
(b) Mixtures observed using population-based genotyping will be reported as ‘E138A/K’, whereas these will be reported separately as ‘E138A’ and ‘E138K’ using NGS. 


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[Note to programmer: Amino acids are listed in numeric order; population-based genotyping included as numbers might be different from main analysis. To simplify the 
analysis of population-based genotype mixtures, include the count if the mixture includes a variant from the NGS analysis. Also, if there is more than one variant detected 
by NGS, these should be included in the listed row. The example: K101E + E138A + E138K + Y181C might be represented in the population-based genotype as K101E + 
E138A/K + Y181C the E138A + E138K would count as one mutation, but subsequently broken down by sequence. The example shows all possible population-based 
genotypes, only ones that apply should be included.] 
 
 
 


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Table 14.3.9.3.1 
Summary of Phenotypic Susceptibility to Dapivirine and Other NNRTIs by Population-based Genotype 
Virology Population 
 
All Viruses 
Dapivirine 
Efavirenz  
Etravirine   
Nevirapine   
Rilpivirine   
N 
XX 
XX 
XX 
XX 
XX 
IC50 (nM) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Fold change (a) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Wild-type viruses (b) 
N 
XX 
XX 
XX 
XX 
XX 
IC50 (nM) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
 
Fold change (a) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 


IPM 032 Virology Addendum SAP 
Table and Listing Shells, Version 1.0 
Version Dated: 24 May 2021 
Page 14 of 21 
 
Viruses with any NNRTI RAM 
N 
XX 
XX 
XX 
XX 
XX 
IC50 (nM) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Fold change (a) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Viruses with one NNRTI RAM 
N 
XX 
XX 
XX 
XX 
XX 
IC50 (nM) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Fold change (a) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Viruses with two NNRTI RAMs 
N 
XX 
XX 
XX 
XX 
XX 
IC50 (nM) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 


IPM 032 Virology Addendum SAP 
Table and Listing Shells, Version 1.0 
Version Dated: 24 May 2021 
Page 15 of 21 
 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Fold change (a) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Viruses with three or more NNRTI RAMs 
N 
XX 
XX 
XX 
XX 
XX 
IC50 (nM) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Fold change (a) 
Geometric mean (SD) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
x.xx (x.xxx) 
(25th/median/75th) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(x.xx/x.xx/x.xx) 
(Min,max) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
(x.xx/xx.xx) 
Viruses with A98G 
etc. 
Viruses with K101E 
etc. 
Viruses with K101E + E138A 
etc. 
(a) Fold change = IC50/IC50wild-type reference control. 
(b) Mutations are included from population-based genotyping results (minority species mutations are less likely to influence phenotypes). 
 
 
 


IPM 032 Virology Addendum SAP 
Table and Listing Shells, Version 1.0 
Version Dated: 24 May 2021 
Page 16 of 21 
 
 
Table 14.3.9.4.1 
Summary of Number of Participants with an Amino Acid Change from Reference per Residue in the RT Region Among HIV-1 Seroconversions 
using Population-Based Genotyping (All Seroconversion ± 14-Days Data) 
Virology Population 
 
 
Population-based Genotype 
n (%) 
Participants with a population-based genotyping assessment at seroconversion time point (N) 
XX 
Stanford Number of NNRTI RAMs per participant (a) 
None 
XX (X.X%) 
Any 
X (X.X%) 
One 
X (X.X%) 
Two  
X (X.X%) 
Three or more 
X (X.X%) 
Average 
0.XX 
Stanford NNRTI resistance mutation combinations (b) 
A98G 
X (X.X%) 
K101E 
X (X.X%) 
K101E + E138A 
X (X.X%) 
K101E + E138A/K + Y181C 
X (X.X%) 
etc. 
N = Number of participants with data; n = number of participants with that observation; NNRTI = Non-nucleoside Reverse Transcriptase Inhibitor.  
The percentage calculation is based on the total number of participants with a successful population-based genotyping assessment at seroconversion.  
The Stanford HIV-1 Drug Resistance Database version 8.4 (dated 2017-06-16) was used.  
(a) Instances of mixtures among the population-based genotypes that include one or more NNRTI RAM, are counted as if the mutation with the greatest drug resistance 
score was present. 


IPM 032 Virology Addendum SAP 
Table and Listing Shells, Version 1.0 
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Page 17 of 21 
 
LISTING SHELLS 
 
Listing 
Title 
16.2.8.20 
Next Generation Sequencing and Phenotype Susceptibility Data 
16.2.8.20.1 
Next Generation Sequencing: Listing of All Available Data 
16.2.8.20.2 
Next Generation Sequencing: Listing of Detected NNRTI Resistance-associated 
Mutations 
16.2.8.20.4 
Phenotypic Data: Listing of All Available Data 
16.2.8.20.5 
Genotypic Interpretations with Phenotypic Data: Full Listing for HIV-1 
Seroconverters 
Note: Population-based genotyping data are listed in the IPM 032 CSR Listings. 
 


IPM 032 Virology Addendum SAP 
Table and Listing Shells, Version 1.0 
Version Dated: 24 May 2021 
Page 18 of 21 
 
 
 
Listing 16.2.8.20.1 
Next Generation Sequencing: Listing of All Available Data 
Safety Population 
 
PID (a) 
Sample Date 
Days (b) Days (c) 
Visit Day 
(d) 
Log10 HIV-1 
RNA 
(copies/mL) 
Number  
UMI with 
Consensus 
Sample 
Sensitivity 
(%) 
Valid Result 
Amino acid (% UMI) Change from 
Reference (e) 
XXX-XXXXXX 
DDMMMYYYY XX 
XX 
XXX 
X.XXX 
XXXX 
X 
Yes/No 
YxxX (xx), YxxX (xx), YxxxX 
(xx),…. 
etc. 
(a) PIDs infected on enrolment indicated with 'α'; PIDs with seroconversion off DVR-004 use indicated with 'β'. 
(b) Days since seroconversion (negative values indicate evaluation prior to seroconversion). 
(c) Days since first HIV-1 RNA detection. 
(d) Visits indicated with a * are not within 14 days of the seroconversion time point. 
(e) Reference sequence: HXB2 (accession number K03455-1).  
The sequenced region contains RT amino acids 81 – 150, 152 - 212. NGS analyses are considered exploratory. 
[Notes to programmer: Amino acids are listed in numeric order (Note e); choose appropriate markers for different populations (Note a).] 
 
 
 
 
 


IPM 032 Virology Addendum SAP 
Table and Listing Shells, Version 1.0 
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Page 19 of 21 
 
Listing 16.2.8.20.2 
Next Generation Sequencing: Listing of Detected NNRTI Resistance-associated Mutations 
Safety Population 
 
PID (a) 
Sample Date 
Days (b)  
Days (c)  
Visit Day  
Visit (d) 
Number 
UMI with 
Consensus 
Sample 
Sensitivity 
(%) 
Number 
of 
Mutations 
NNRTI RAMs (e) 
XXX-
XXXXXX 
DDMMMYYYY 
XX 
XX 
XXX 
Month 
XX/ 
Week XX 
XXXX 
X 
X 
YxxZ (xx), YxxZ (xx),…. 
XXX-
XXXXXX 
DDMMMYYYY 
XX 
XX 
XXX 
Month 
XX/ 
Week XX 
XXXX 
X 
X 
None 
XXX-
XXXXXX 
DDMMMYYYY 
XX 
XX 
XXX 
Month 
XX/ 
Week XX 
XXXX 
X 
X 
No Test 
etc. 
Table includes PIDS only if NNRTI RAMs were detected in NGS analysis. 
(a) PIDs infected on enrolment indicated with 'α'; PIDs with seroconversion off DVR-004 use indicated with 'β'.  
(b) Days since seroconversion (negative values indicate evaluation prior to seroconversion). 
(c) Days since first HIV-1 RNA detection. 
(d) Visits indicated with a * are not within 14 days of the seroconversion time point. 
(e) Mutations reported according to Stanford HIVdb algorithm version 8.4 (see SAP). 
The sequenced region contains RT amino acids 81 – 150, 152 - 212. NGS analyses should be considered exploratory. 
[Notes to programmer: Amino acids are listed in numeric order (Note e); choose appropriate markers for different populations (Note a).] 
 
 
 


IPM 032 Virology Addendum SAP 
Table and Listing Shells, Version 1.0 
Version Dated: 24 May 2021 
Page 20 of 21 
 
Listing 16.2.8.20.4 
Phenotypic Data: Listing of All Available Data 
Safety Population 
 
DPV 
EFV 
ETR 
NVP 
RPV 
PID 
Sample Date 
NNRTI 
RAMs 
Result 
ID 
IC50 
(nM) 
FC (a) 
 
IC50 
(nM) 
FC (a) 
 
IC50 
(nM) 
FC (a) 
 
IC50 
(nM) 
FC (a) 
 
IC50 
(nM) 
FC (a) 
XXX-
XXXXXX 
DDMMMYYYY 
None 
1 
x.xx 
(x.xx) 
 
x.xx 
(x.xx) 
 
x.xx 
(x.xx) 
 
x.xx 
(x.xx) 
 
x.xx 
(x.xx) 
2 
x.xx 
(x.xx) 
 
 
 
 
3 
x.xx 
(x.xx) 
 
 
 
 
Avg 
x.xx 
(x.xx) 
x.x 
 
x.xx 
(x.xx) 
x.x 
 
x.xx 
(x.xx) 
x.x 
 
x.xx 
(x.xx) 
x.x 
 
x.xx 
(x.xx) 
x.x 
etc. 
 
 
 
 
 
 
 
 
DPV = Dapivirine; EFV = Efavirenz; ETR = Etravirine; FC: Fold change; IC50: 50% Inhibitory concentration; NNRTI: Non-nucleoside reverse transcriptase inhibitor; NVP 
= Nevirapine; PID: Participant identifier; RAM: Resistance-associated mutation; RPV = Rilpivirine 
(a) FC = IC50/IC50CONTROL (Control IC50 [nM] range: DPV: n = X:  X.XX - X.XX; EFV: n = X:  X.XX - X.XX ; ETR: n = X:  X.XX - X.XX; NVP: n = X:  X.XX - 
X.XX; RPV: n = X:  X.XX - X.XX). n: number of runs to complete the analysis. 
(b) IC50 sample and (IC50 reference virus) are given.  
[Note to programmer: Order by PID and then by NNRTI RAMs with 'None' first, then mutations in numeric order. Note the reference virus will be different from that in 
IPM 027 - a single lab-strain has been used per run.] 
 
 
 


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Page 21 of 21 
 
Listing 16.2.8.20.5 
Genotypic Interpretations with Phenotypic Data: Full Listing for HIV-1 Seroconverters 
Safety Population 
 
NNRTI RAMs 
NNRTI Genotypic 
Susceptibility 
(Population-based sequencing) 
(a) 
Phenotype 
PID 
Sample Date 
Population 
NGS 
NNRTI 
IC50 (nM) 
FC (b) 
XXX-XXXXXX 
DDMMMYYYY 
None 
None 
Dapivirine 
N/A 
X.XX 
X.X 
Efavirenz 
XX (YYY) 
X.XX 
X.X 
Etravirine 
XX (YYY) 
X.XX 
X.X 
Nevirapine 
XX (YYY) 
X.XX 
X.X 
Rilpivirine 
XX (YYY) 
X.XX 
X.X 
XXX-XXXXXX 
DDMMMYYYY 
YXXY 
YXXY 
Dapivirine 
N/A 
X.XX 
X.X 
Efavirenz 
XX (YYY) 
X.XX 
X.X 
Etravirine 
XX (YYY) 
X.XX 
X.X 
Nevirapine 
XX (YYY) 
X.XX 
X.X 
Rilpivirine 
XX (YYY) 
X.XX 
X.X 
etc. 
HLR = High-level resistant; Interm = Intermediate resistant; LLR = Low-level resistant; N/A = Not applicable; NNRTI = Non-nucleoside Reverse Transcriptase Inhibitor; 
PLLR = Potential low-level resistant; RAM: Resistance-associated mutation; Sus = Susceptibility. 
(a) Stanford HIVdb algorithm version 8.4 drug resistance score (interpretation: Sus, PLLR, LLR, Interm, HLR). 
(b) FC = IC50/IC50Control (Control IC50 [nM] range: DPV: n = X:  X.XX - X.XX; EFV: n = X:  X.XX - X.XX ; ETR: n = X:  X.XX - X.XX; NVP: n = X:  X.XX - X.XX; 
RPV: n = X:  X.XX - X.XX)  
[Note to programmer: Order by PID then by NNRTI RAMs with 'None' first, then mutations in numeric order (as per Phenotype Listing 16.2.8.20.4).] 
 

Prot_001.pdf: 
 
IPM 032 
Protocol 
 
CONFIDENTIAL 
CLIN-TEM-GEN-0001.00, 13Jan2016 
 
Page 1 of 1 
 
NCT02862171 
 
IPM 032 
 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF AND 
ADHERENCE TO THE DAPIVIRINE (25 mg) VAGINAL RING-004 IN HEALTHY, HIV-NEGATIVE 
WOMEN  
 
• 
Protocol Version 2.0 Amendment 2.0 dated 16 January 2017 
 


IPM 032 
 
   16 January 2017 
Version 2.0 Amendment 2.0 
 
Page 1 of 83 
Restricted * Confidential – Limited Access* 
IPM 032 
 
Version 2.0 Amendment 2.0 
 
16 January 2017 
 
 
 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF AND 
ADHERENCE TO THE DAPIVIRINE (25 mg) VAGINAL RING-004 IN HEALTHY, 
HIV-NEGATIVE WOMEN  
 
 
 
 
Phase IIIb 
 
 
 
 
SPONSOR: 
International Partnership for Microbicides 
8401 Colesville Road, Suite 200 
Silver Spring, MD 20910 U.S.A. 
Phone: 1-301-608-2221 
Fax: 1-301-608-2241 
 
After 01 June 2017:   
International Partnership for Microbicides  
8405 Colesville Road, Suite 600 
Silver Spring, MD 20910 USA 
Phone: 1-301-608-2221 
Fax: 1-301-608-2241 
 
 
 
 
 
 
 
 
 
 
 
 


IPM 032 
 
   16 January 2017 
Version 2.0 Amendment 2.0 
 
Page 2 of 83 
Restricted * Confidential – Limited Access* 
SIGNATURE PAGE 
 
 
IPM 032 
 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF 
AND ADHERENCE TO THE DAPIVIRINE (25 mg) VAGINAL RING-004 IN 
HEALTHY, HIV-NEGATIVE WOMEN 
 
I have read this protocol and appendices and agree to conduct the trial as stipulated and 
in compliance with the principles of the World Medical Association Declaration of 
Helsinki, the International Conference on Harmonisation (ICH) Good Clinical Practice 
(GCP) guidelines, and all applicable regulations and guidelines. 
 
 
 
__________________________________   
__________________________ 
Investigator Signature 
 
 
 
Date 
 
 
__________________________________  
___________________________ 
Investigator Name (Printed)  
 
 
Research Centre Name 
 
 
 
On behalf of the International Partnership for Microbicides, I confirm that the sponsor will 
comply with all obligations as detailed in all applicable regulations and guidelines. I will 
ensure that the investigator is informed of all relevant information that becomes available 
during the conduct of this trial. 
 
 
____________________________________ 
_____________________________ 
Chief Medical Officer Signature 
 
 
Date 
 
 
Annalene Nel, MBChB, PhD  
 
 
 
Chief Medical Officer Name (Printed) 
 
 
 
 


IPM 032 
 
   16 January 2017 
Version 2.0 Amendment 2.0 
 
Page 3 of 83 
Restricted * Confidential – Limited Access* 
TABLE OF CONTENTS 
 
1. 
Introduction ................................................................................................................ 22 
1.1. Background ........................................................................................................ 22 
1.2. Dapivirine Vaginal Ring ...................................................................................... 23 
1.3. Nonclinical Studies ............................................................................................. 23 
1.4. Clinical Trials ...................................................................................................... 25 
1.5. Rationale for Protocol IPM 032 .......................................................................... 28 
2. 
Trial Objectives .......................................................................................................... 29 
2.1. Trial Objectives ................................................................................................... 29 
2.2. Trial Endpoints and Assessments ..................................................................... 30 
3. 
Overall Trial Design ................................................................................................... 31 
3.1. Trial Design ........................................................................................................ 31 
3.2. Trial Duration ...................................................................................................... 32 
3.3. Trial Population .................................................................................................. 32 
4. 
Trial Visits and Procedures ....................................................................................... 34 
4.1. Pre-screening ..................................................................................................... 34 
4.2. Screening Visit ................................................................................................... 34 
4.3. Enrolment Visit ................................................................................................... 36 
4.4. Trial Visits (Monthly research centre visits for the first one to three months, and 
3-monthly research centre visits thereafter) ............................................................ 37 
4.5. Last Product Use Visit (LPUV) or Early Discontinuation Visit ........................... 39 
4.6. Exit Visit .............................................................................................................. 40 
4.7. Unscheduled Visits ............................................................................................. 40 
4.8. Missed and Late Visits ....................................................................................... 41 
4.9. Protocol Deviations ............................................................................................ 41 
4.10.  Early Discontinuation Visits ........................................................................... 42 
4.11.  Premature Discontinuation of the Trial .......................................................... 42 
5. 
Trial Procedure Details .............................................................................................. 43 
5.1. Informed Consent ............................................................................................... 43 
5.2. Comprehension Assessment Checklist ............................................................. 44 
5.3. HIV Counselling .................................................................................................. 44 
5.4. HIV Testing and Management ........................................................................... 45 


IPM 032 
 
   16 January 2017 
Version 2.0 Amendment 2.0 
 
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5.5. Contraceptive Counselling and Management of Contraception ........................ 48 
5.6. Pregnancy Testing and Management ................................................................ 49 
5.7. Demographics and Medical History ................................................................... 50 
5.8. Physical Examination ......................................................................................... 50 
5.9. Pelvic Examination ............................................................................................. 50 
5.10.  Laboratory testing for safety assessments and urine dipstick analysis ........ 51 
5.11.  STI Testing and Management ....................................................................... 51 
5.12.  Cervical Cytology ........................................................................................... 52 
5.13.  Vaginal Ring Dispensing ................................................................................ 52 
5.14.  Vaginal Ring Insertion and Ring Removal ..................................................... 53 
5.15.  Vaginal Ring Adherence Counselling ............................................................ 53 
5.16.  Qualitative Behavioural Assessments ........................................................... 54 
5.17.  Quantitative Behavioural Assessments ......................................................... 54 
5.18.  Sample Storage and Analysis ........................................................................ 55 
5.19.  Screening Identification (SCR-ID) and Participant Identification (PID) 
Numbers ................................................................................................................... 55 
5.20.  Diary cards ..................................................................................................... 55 
5.21.  Reimbursement .............................................................................................. 56 
5.22.  Participant Compensation .............................................................................. 56 
5.23.  Participant Responsibility ............................................................................... 56 
5.24.  Study Operations Manual (SOM) .................................................................. 56 
6. 
Investigational Product .............................................................................................. 56 
6.1. Investigational Product Composition ................................................................. 56 
6.2. Packaging and Labelling .................................................................................... 57 
6.3. Investigational Product Storage ......................................................................... 57 
6.4. Investigational Product Administration ............................................................... 57 
6.5. Investigational Product Expulsion or Loss ......................................................... 58 
6.6. Retrieval of Investigational Product ................................................................... 58 
6.7. Investigational Product (IP) Accountability ........................................................ 58 
6.8. Concomitant Medications and Products ............................................................ 59 
7. 
Adverse Events ......................................................................................................... 59 
7.1. Definition ............................................................................................................. 59 
7.2. Assessment of Adverse Event Severity ............................................................. 60 
7.3. Relationship to Investigational Product.............................................................. 60 
7.4. Serious Adverse Event ....................................................................................... 61 
7.5. Immediately Reportable Events ......................................................................... 62 
7.6. Safety Monitoring ............................................................................................... 63 
7.7. Data Handling at Research Centres .................................................................. 63 
7.8. Source Data Verification .................................................................................... 64 
8. 
Statistical Methods .................................................................................................... 64 


IPM 032 
 
   16 January 2017 
Version 2.0 Amendment 2.0 
 
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8.1. Trial Endpoints ................................................................................................... 64 
8.2. Primary Trial Hypotheses ................................................................................... 64 
8.3. Sample Size and Power Calculations ................................................................ 65 
8.4. Statistical Analyses ............................................................................................ 65 
8.5. Data and Safety Monitoring Board ..................................................................... 68 
8.6. Handling of Missing Data and Dropouts ............................................................ 68 
9. 
Investigator Requirements ........................................................................................ 69 
9.1. Trial Initiation ...................................................................................................... 69 
9.2. Institutional Review Boards or Independent Ethics Committee Approval ......... 69 
9.3. Trial Monitoring and Audits ................................................................................ 69 
9.4. Case Report Forms (CRFs) ............................................................................... 70 
9.5. Disclosure of Data .............................................................................................. 70 
9.6. Record Retention ............................................................................................... 70 
10.  Ethical Considerations ............................................................................................... 70 
10.1.  Ethical Review ................................................................................................ 70 
10.2.  Reporting and Management of Social Harms related to trial participation ... 71 
10.3.  Community Engagement ............................................................................... 71 
11.  Publications ............................................................................................................... 71 
12.  References ................................................................................................................ 72 
APPENDIX A: SCHEDULE OF PROCEDURES .............................................................. 74 
APPENDIX B: HIV TESTING ALGORITHM ..................................................................... 77 
APPENDIX C: VISIT SCHEDULE AND APPROXIMATE BLOOD VOLUMES ............... 82 
APPENDIX D: TRIAL DESIGN ......................................................................................... 83 
 


IPM 032 
 
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ACRONYMS AND ABBREVIATIONS 
AE  
Adverse Event  
AIDS  
Acquired Immunodeficiency Syndrome  
ALT  
Alanine aminotransferase  
ARV  
Antiretroviral  
AST  
Aspartate aminotransferase  
AUC  
Area Under Plasma Concentration-time Curve  
BV 
Bacterial Vaginosis  
b.i.d. 
“bis in die”/twice a day 
ºC 
Degree Celsius 
CI 
Confidence Interval 
CNS 
Central Nervous System 
CRF  
Case Report Form  
CT 
Chlamydia Trachomatis 
DAIDS  
Division of Acquired Immunodeficiency Syndrome  
DAPY  
Di-amino pyrimidine  
DP-ID 
Decliner Participant Identification 
DSMB  
Data and Safety Monitoring Board  
DVR 
Dapivirine Vaginal Ring-004 
EC50  
50% Effective Inhibition Concentration 
FBC  
Full Blood Count  
FDA  
Food & Drug Administration (U.S.)  
GCP  
Good Clinical Practice  
HIV  
Human Immunodeficiency Virus  
Hu-SCID 
Humanized Severe Combined Immunodeficient  
ICF 
Informed Consent Form 
ICH  
International Conference on Harmonisation  
IEC  
Independent Ethics Committee  
IB 
Investigator’s Brochure 
IP 
Investigational Product 
IPM  
International Partnership for Microbicides  
IRB  
Institutional Review Board  
IRE  
Immediately Reportable Event  
ITT  
Intent-To-Treat 
LPUV 
Last Product Use Visit 
MedDRA 
Medical Dictionary for Regulatory Activities  
MTD  
Maximum Tolerated Dose  
MTN  
Microbicide Trials Network  
NAAT 
Nucleic Acid-Amplification Testing 
NG 
Neisseria Gonorrhoeae 
NNRTI  
Non-nucleoside Reverse Transcriptase Inhibitor  
NOAEL 
No Adverse Effect Level 
PCR  
Polymerase Chain Reaction  
PID  
Participant Identification  
PMTCT  
Prevention of Mother-to-Child Transmission of HIV  
PT 
Preferred Term 
RNA  
Ribonucleic Acid  
RPR  
Rapid Plasma Reagin  
RT 
Reverse transcriptase 
SAE  
Serious Adverse Event  


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SAP  
Statistical Analysis Plan  
SCR-ID 
Screening Identification  
SOC 
System Organ Class 
SOM 
Study Operations Manual 
SOP 
Standard Operating Procedure 
STI  
Sexually Transmitted Infection 
TEAE  
Treatment Emergent Adverse Event  
TPHA  
Treponema Pallidum Haemagglutination Test  
TPPA  
Treponema Pallidum Particle Agglutination Assay  
TV 
Trichomonas Vaginalis 
UNAIDS  
Joint United Nations Programme on HIV/AIDS  
WHO  
World Health Organization 
 
 
 
 
 
 


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PROTOCOL SYNOPSIS 
IPM 032 
 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF AND 
ADHERENCE TO THE DAPIVIRINE (25 mg) VAGINAL RING-004 IN HEALTHY, 
HIV-NEGATIVE WOMEN 
 
BACKGROUND:  
The Phase III clinical program of Dapivirine Vaginal Ring-004, 
containing 25 mg of dapivirine, consisted of the MTN-020 and 
IPM 027 clinical trials. These trials were conducted in South Africa, 
Uganda, Zimbabwe and Malawi, to assess the safety and efficacy 
of the Dapivirine Vaginal Ring-004 in preventing the acquisition of 
HIV-1 infection through male to female transmission during vaginal 
sexual intercourse in healthy, HIV-negative women. 
 
The results of the IPM 027 and MTN-020 trials demonstrated that 
the Dapivirine Vaginal Ring-004 is safe and reduced the risk of 
acquiring HIV-1 infection1,2. A lower HIV-1 risk reduction was 
observed in women ≤21 years of age in IPM 027 (the age effect 
was not statistically significant). Results were communicated to the 
relevant local and international regulatory authorities, IRBs/IECs, 
community representatives, participants and key stakeholders, as 
appropriate. 
 
IPM 032, a Phase IIIb follow-on trial to IPM 027, has been 
designed as an open-label clinical trial in women who participated 
in IPM 027; two additional cohorts of Dapivirine Vaginal Ring-004-
naïve (DVR-naïve) young women will be enrolled  in order to 
understand younger women’s unique challenges in using HIV 
prevention methods.  Additional safety data will be collected and 
adherence to ring use will be evaluated in healthy, HIV-negative 
women with monthly visits (up to a maximum of three monthly 
visits) followed by 3-monthly follow-up visits over 12 months. 
Behavioural data will be collected to support the potential 
introduction of a microbicide as a public health intervention and to 
assist with future program development. 
 
OBJECTIVES: 
Primary, secondary and exploratory objectives will compare data 
between former IPM 027 participants and DVR-naïve cohorts. The 
analysis will be described in the Statistical Analysis Plan.   
 
The Primary Trial Objectives are: 
 
1. To assess the safety profile of the 25 mg Dapivirine Vaginal 
Ring-004, when inserted at monthly intervals, in an open-label 
trial  
2. To assess adherence to the use of the 25 mg Dapivirine 
Vaginal Ring-004 inserted at monthly intervals, in an open-
label trial  
 


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The Secondary Trial Objectives are: 
 
1. To assess the incidence of HIV-1 seroconversion 
2. To assess the frequency of HIV-1 drug resistance in women 
who acquire HIV-1 infection 
 
 
 
 
 
 
The Exploratory Trial Objectives are: 
 
1. 
To assess the feasibility of 3-monthly follow-up visits, as a 
possible schedule for post-licensure vaginal ring clinical 
follow-up 
2. 
To explore the correlation between drug concentrations and 
results from the visual inspection of the returned vaginal rings 
by research staff between the monthly and 3-monthly research 
centre follow-up schedules 
3. 
To determine the proportion of participants electing to undergo 
HIV rapid tests at the research centres between scheduled 3-
monthly visits 
4. 
To characterize the IPM 027 participants who decline 
enrollment into IPM 032 (Decliner Population) 
5. 
To explore self-reported acceptability of and adherence to the 
25 mg Dapivirine Vaginal Ring-004.  
 
ENDPOINTS AND ASSESSMENTS:  
 
 
The primary endpoints are: 
 
1. 
Safety  
 
All Adverse Events (AEs) assessed by the investigator to 
be related to the Dapivirine Vaginal Ring-004 
 
All Grade 3 and 4 AEs 
 
All Serious Adverse Events (SAEs) 
 
2. 
Adherence 
 
Residual amounts of dapivirine in returned rings; and/or 
dapivirine concentrations in plasma and/or dapivirine 
concentrations in vaginal fluid  
 
 
The primary endpoints will be assessed through: 
 
1. 
Safety  
 
All product-related AEs, Grade 3 or 4 AEs, SAEs, physical 
examination, 
gynaecological 
assessments, 
including 
pelvic/speculum examination, laboratory tests and other 
indicated investigations 


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2. 
Adherence 
 
Determined dapivirine residual amounts in returned used 
vaginal rings and/or 
 
Measured concentrations of dapivirine in plasma and/or 
 
Measured concentrations of dapivirine in vaginal fluids  
 
 
The secondary endpoints are: 
 
 
The HIV-1 seroconversion rate per 100 woman-years of 
product use at the end of the vaginal ring use period 
 
HIV-1 drug resistance mutations among participants who 
acquire HIV-1 infection  
 
 
The secondary endpoints will be assessed through: 
 
 
Rapid and specialised laboratory testing according to a 
pre-specified HIV testing algorithm 
 
Viral genotype resistance testing methods which include 
sensitive methods to detect low frequency drug-resistant 
variants 
 
  
 
The exploratory endpoints are: 
 
 
Feasibility of 3-monthly clinical follow-up schedule 
 
Dapivirine residual amounts in returned used vaginal rings 
and/or dapivirine concentrations in blood and/or vaginal 
fluid in correlation with results from the visual inspection 
of the returned used vaginal rings by research staff 
 
Proportion of participants opting for HIV rapid tests at the 
research centre between scheduled 3-monthly research 
centre follow-up visits 
 
Characteristics of IPM 027 participants who decline 
enrollment into IPM 032 (Decliner Population) and 
reasons for declining 
 
The proportion of women who report the use of the 
vaginal ring as acceptable 
 
Participant self-reported patterns of ring use 
 
 
The exploratory endpoints will be assessed through: 
 
 
Participant report of feasibility regarding a 3-monthly 
clinical follow-up schedule (Participant Questionnaire)    
 
Number of women opting not to receive two additional 


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rings at the 3-monthly visits  
 
Proportion of returned rings (used and unused) during the 
3-monthly clinical follow-up schedule 
 
Dapivirine residual amounts in returned used vaginal rings 
and/or dapivirine concentrations in blood and/or vaginal 
fluid 
 
Visual inspection of the returned used vaginal rings by 
research centre staff 
 
Number of participants undergoing HIV rapid tests at the 
research centre between scheduled 3-monthly research 
centre follow-up visits 
 
Questionnaires and qualitative data regarding reasons for 
declining participation, ring acceptability and self-reported 
patterns of ring use.   
 
TRIAL DESIGN:  
IPM 032 is a Phase IIIb, multi-centre follow-on open-label trial to 
evaluate the continued adherence to and safety of the Dapivirine 
Vaginal Ring-004 inserted at monthly intervals in healthy, HIV-
negative women who have participated in the IPM 027 Phase III 
Dapivirine Vaginal Ring-004 trial as well as in two additional 
cohorts of DVR-naïve young women. All women who have 
participated in IPM 027 and are HIV-negative at screening for IPM 
032 will be eligible. Up to 1400 former IPM 027 participants will be 
enrolled. Two additional cohorts of women aged ≥18 to ≤21 years 
and >21 to <25 years, who have not previously used the Dapivirine 
Vaginal Ring-004 (DVR-naïve Cohorts), will be enrolled. An 
estimated 300 participants will be enrolled in each of these two 
additional cohorts. The total estimated enrollment in the trial will be 
approximately 2000 participants.      
 
All participants will attend a follow-up visit one month after 
enrolment. Following this visit, at the investigator’s discretion, a 
participant can continue on a 3-monthly visit schedule. Monthly 
visits may however be extended up to the first three months of 
participation. Once the 3-monthly trial visit schedule commences, 
three rings will be dispensed to the participant.  One ring will be 
self-inserted at the research centre and two additional rings will be 
dispensed for the participant to take home, or dispensing will take 
place as arranged with the participant. At any point following the 
first 3 months of trial participation, participants may opt to continue 
using the ring (Ring Users) or to not use the ring (Ring Non-users) 
while continuing in the trial. Ring Non-users may initiate 
continuous use of the ring again at any stage during their trial 
participation.  
 
 
  
TRIAL DURATION:  Each participant will engage in the screening process for up to 45 
days prior to enrolment and will use the Dapivirine Vaginal Ring-


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004 for a period of up to 12 months. IPM will have the option to 
extend this trial period.  
 
Each participant will have an exit visit approximately 1-2 months 
after ring discontinuation, to assess safety and identify HIV 
seroconversions after product discontinuation. Exit visits will be 
optional for participants who are Ring Non-users at the point of trial 
termination. 
 
POPULATION AND SAMPLE SIZE: 
 
Approximately 2000 HIV-negative women who understand the trial 
and can provide informed consent are expected to enrol in this 
open-label trial. This includes up to 1400 women who participated 
in the IPM 027 Phase III Dapivirine Vaginal Ring-004 trial and two 
additional cohorts of approximately 300 women each, ≥18 to ≤21 
years and >21 to <25 years respectively, who have not used the 
Dapivirine Vaginal Ring-004 previously (DVR-naïve Cohorts).  
 
 
Former IPM 027 participants who decline enrolment in IPM 032 
(Decliner Population) and who meet the decliner population 
enrolment criteria will be invited to complete a questionnaire 
either in person or telephonically, following written informed 
consent. A subset of these women will be invited to complete 
in-depth interviews and/or focus group discussions.  
 
 
INCLUSION CRITERIA – WOMEN PREVIOUSLY ENROLLED IN IPM 027: 
Women must meet all of the following criteria to be eligible for trial 
enrolment: 
 
1. 
Previously enrolled in the IPM 027 trial  
2. 
Available for all visits and consent to follow all procedures 
scheduled for the trial 
3. 
Using an effective method of contraception at the 
Enrolment Visit, and intending to use an effective 
contraceptive method for the duration of trial participation, 
unless post-menopausal with no history of menses for 
one year prior to screening  
4. 
HIV-negative as determined by the HIV algorithm applied 
at Screening/Pre-Enrolment 
5. 
Willing to refrain from participation in another research 
trial using drugs, vaccines, medical devices and 
microbicides for the duration of the IPM 032 trial 
6. 
Willing to provide adequate locator information for trial 
retention purposes and be reachable per local standard 
procedures (e.g. by home visit or telephone; or via family 
or close neighbour contacts); confidentiality to be 
maintained 
 


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EXCLUSION CRITERIA – WOMEN PREVIOUSLY ENROLLED IN IPM 027: 
Women who meet any of the following criteria are NOT eligible to 
enrol in the trial: 
 
1. 
Investigational product use permanently discontinued in 
response to an AE (where the AE was considered related 
to investigational product) or safety-related concern while 
taking part in the IPM 027 trial  
2. 
Currently pregnant, intending to become pregnant, or 
currently breast-feeding 
3. 
Known drug abuse or alcohol dependence in the 12 
months prior to screening 
4. 
Participated in another research trial (other than IPM 027) 
using drugs, medical devices, microbicides or oral pre-
exposure prophylaxis agents within 30 days prior to 
screening 
5. 
Any new illness or condition(s), chronic condition(s) or 
abnormal laboratory finding(s) that, in the opinion of the 
investigator, might put the participant at risk, or interfere 
with the trial objectives or the participant’s adherence to 
trial requirements 
 
INCLUSION CRITERIA – DVR-NAÏVE COHORTS: 
Women must meet all of the following criteria to be eligible for trial 
enrolment: 
 
1. 
Healthy women ≥18 and <25 years of age, at screening, 
who can provide written informed consent  
2. 
Not used the Dapivirine Vaginal Ring-004 previously 
3. 
Self-reported sexually active (defined as an average of at 
least one penetrative penile-vaginal coital act per month 
for the last 3 months prior to screening) 
4. 
Available for all visits and consent to follow all procedures 
scheduled for the trial 
5. 
Using an effective method of contraception at the 
Enrolment Visit, and intending to use an effective 
contraceptive method for the duration of trial participation 
unless surgically sterilised 
6. 
HIV-negative as determined by the HIV algorithm applied 
at Screening/Pre-Enrolment 
7. 
Willing to refrain from participation in another research 
trial using drugs, vaccines, medical devices and 
microbicides for the duration of the IPM 032 trial 
8. 
Willing to provide adequate locator information for trial 
retention purposes and be reachable per local standard 
procedures (e.g. by home visit or telephone; or via family 
or close neighbour contacts); confidentiality to be 
maintained. 


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EXCLUSION CRITERIA – DVR-NAÏVE COHORTS: 
Women who meet any of the following criteria are NOT eligible to 
enrol in the trial: 
 
1. Currently pregnant or intending to become pregnant, or 
currently breast-feeding 
2. Known drug abuse or alcohol dependence in the 12 months 
prior to screening 
3. Participated in another research trial using drugs, vaccines, 
microbicides or medical devices within 30 days prior to 
screening 
4. Women with Grade 3 cervical cytology findings or Grade 3 
intraepithelial neoplasia by biopsy (histology result) at 
screening  
5. Any history of anaphylaxis or severe allergy resulting in 
angioedema; or a history of sensitivity/allergy to latex or a 
silicone elastomer 
6. Any illness or condition(s), chronic condition(s) or abnormal 
laboratory finding(s) that, in the opinion of the investigator, 
might put the participant at risk, or interfere with the trial 
objectives or the participant’s adherence to trial requirements. 
 
 
INCLUSION CRITERIA – IPM 032 DECLINER POPULATION: 
Women must meet all of the following criteria to be eligible for 
Decliner Population behavioural assessments: 
 
1. 
Previously enrolled in IPM 027  
2. 
Eligible for screening in IPM 032 (i.e. HIV-negative at last 
IPM 027 trial visit, investigational product use NOT 
permanently discontinued in response to an AE (where 
the AE was considered related to the investigational 
product) or a safety-related concern while taking part in 
the IPM 027 trial) 
3. 
Declines enrollment into IPM 032  
4. 
Able and willing to provide written informed consent  
5. 
Able 
and 
willing 
to 
perform 
decliner 
population 
behavioural assessments.  
 
METHODS: 
Pre-screening  
As part of participant outreach and recruitment strategies, study 
staff 
may 
pre-screen 
potential 
trial 
participants 
either 
telephonically, on-site or at off-site locations. Study staff will 
explain the trial to potential participants and determine basic 
elements of eligibility which will be confirmed during the on-site 
screening visits. Interested participants will be scheduled for an 


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on-site screening visit. 
  
Decliner Population:  
Previous IPM 027 participants who decline participation in IPM 
032 will be asked to provide written informed consent to collect 
information on their reasons for declining participation. If they are 
willing to participate in the questionnaire interview, participants will 
be given the choice of meeting the interviewers at a convenient 
location off-site or at the research centre. Questionnaires may be 
completed telephonically after written informed consent has been 
obtained from the participant.   
 
Reasons for declining participation will be captured in a decliner 
population questionnaire, and may be collected retrospectively. A 
decliner population ID (DP-ID) will be assigned to each participant. 
Written informed consent will be obtained from all participants in 
the decliner population to be contacted for participation in further 
behavioural assessments (e.g. qualitative in-depth interviews 
[IDIs] and/or focus group discussion [FGD]), either on-site or at an 
off-site location. Written informed consent will be obtained prior to 
these IDIs and FGDs.  
 
Screening Visit:  
 
Potential participants who are HIV-negative, who participated in 
IPM 027 or potential participants who are interested in 
participating in the DVR-naïve cohorts, and who provide informed 
consent will be invited to screen for the trial and to enrol in the 
open-label follow-on trial. After informed consent is obtained, a 
SCR-ID number will be assigned to each potential participant for 
identification purposes and the potential participant will be 
screened to assess eligibility for the trial. A comprehension 
checklist will be used to support the informed consent process.   
 
At screening, potential participants will provide information on 
inclusion and exclusion criteria, including locator and basic 
menses information, demographic information, and medical and 
concomitant medication history.  Each potential participant will 
receive a general physical examination and pelvic examination.  
 
All potential participants will be provided with HIV/STI risk-
reduction counselling (including provision of male and/or female 
condoms, should participants wish to receive them), contraceptive 
counselling 
and 
HIV 
pre- 
and 
post-test 
counselling. 
Contraceptives will be provided if necessary, as well as treatment 
and/or referral for sexually transmitted infections (STIs) and other 
findings as necessary. Safety laboratory assessments, urine 
dipstick analysis (microscopy only if clinically indicated), cervical 
sample collection for cytology and testing for pregnancy, HIV, 
STIs, and syphilis will be performed. Blood samples for HIV-1 
RNA PCR and HIV viral genotype resistance testing will be 
collected and stored for retrospective testing subsequent to a 


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confirmed HIV-1 seroconversion. 
 
Enrolment Visit: 
 
At the Enrolment Visit, potential participants will provide 
information on inclusion and exclusion criteria, including locator 
and basic menses information, and medical and concomitant 
medication history.  AEs (post-enrolment) and the occurrence of 
possible social harms will be assessed. 
 
All potential participants will be provided with HIV/STI risk-
reduction counselling (including provision of male and/or female 
condoms, should participants wish to receive them), contraceptive 
counselling and provision of contraceptives (if necessary), HIV 
pre- and post-test counselling and vaginal ring adherence 
counselling. Participants will be provided with feedback on the 
IPM 027 and MTN-020 trial results. Diary cards will be issued with 
instructions for completion. Participants in the DVR-naïve cohorts 
will complete a baseline behavioural questionnaire at enrolment. 
Testing for pregnancy and HIV will be performed. Samples will be 
collected for vaginal pH and vaginal flora testing. Blood samples 
will be collected for storage, and HIV-1 RNA PCR and HIV viral 
genotype resistance testing will be performed retrospectively 
subsequent to confirmed HIV-1 seroconversion.  
 
Eligible women will be assigned a unique PID number. Each 
participant will be provided with vaginal ring use and storage 
instructions and instructed to self-insert a newly dispensed vaginal 
ring.  
 
Trial Visits:  
All participants will provide information on concomitant medication, 
locator details and menses. Participants will receive pre- and post-
test HIV counselling; HIV/STI risk reduction counselling; vaginal 
ring adherence counselling; HIV rapid testing and pregnancy 
testing. Samples will be collected for vaginal pH and vaginal flora 
testing. Male and/or female condoms will be provided at all visits, 
should participants wish to receive them, as part of HIV/STI risk 
reduction 
counselling. 
Contraceptive 
counselling 
and 
contraceptives (if needed) will be provided at all visits. Possible 
occurrence of social harms will be assessed during research 
centre visits.   
 
Blood samples will be collected for storage at each trial visit and 
will be tested retrospectively by HIV-1 RNA PCR and HIV viral 
genotype resistance testing subsequent to confirmed HIV 
seroconversion.  At the point of HIV seroconversion, vaginal ring 
use will be discontinued, and in addition, blood samples will be 
collected according to the HIV testing algorithm.   
 
Blood and vaginal fluid samples will be collected for possible 
measurement of dapivirine concentrations. Returned rings will be 


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visually inspected by research centre staff and may also be 
analysed for residual amounts of dapivirine. Results may be 
shared 
with 
participants 
to 
support 
ring-use 
adherence 
counselling.  
 
Returned diary cards will be reviewed and new diary cards issued 
to participants as applicable. Each participant will be asked to 
complete a Participant Questionnaire at every trial visit.  Ring use 
related questions will not be collected from Ring Non-users. AEs 
will be assessed at all visits post-enrolment. In addition, if clinically 
indicated, safety laboratory assessments, urine dipstick analysis 
(microscopy only if clinically indicated), pelvic examinations, 
cervical sample collection for cytology, physical examinations and 
STI tests will be performed. Treatment and/or referral for STIs and 
other findings may be performed, if required.    
 
At any point following the first 3 months of trial participation, 
participants may opt to continue using the ring (Ring Users) or to 
not use the ring (Ring Non-users) while continuing in the trial. Ring 
Non-users may initiate continuous use of the ring again at any 
stage during their trial participation. Reasons for stopping and 
starting product use will be collected to understand women’s 
choices. 
 
At each trial visit, participants will return used vaginal rings and 
each participant will be instructed to self-insert a newly-dispensed 
vaginal ring and be provided with vaginal ring use and storage 
instructions, should she wish to continue using the vaginal ring. 
Two additional rings will be dispensed once participants 
commence with the 3-monthly trial visit schedule, which the 
participants should self-insert at monthly intervals, at home, until 
the next Trial Visit. Participants who prefer not to have additional 
vaginal rings in their possession may also choose to return and to 
collect the vaginal rings from the research centre at time intervals 
suitable to them, providing a new ring is inserted monthly. HIV 
rapid tests will be offered to participants during these interim visits.  
 
If a participant is unable to attend the next scheduled visit, the 
investigator or designee could dispense additional ring(s) on a 
case-by-case basis. All such circumstances must be documented 
fully by the investigator or designee as described in the IPM 032 
Study Operations Manual (SOM). If a participant requires an 
additional ring at a time other than when they are scheduled to 
receive one, they will be required to attend the clinic for an interim 
visit. 
 
Last product use visit (LPUV):   
At the last product use visit, participants will return any 
used/unused rings; report any medical problems, social harms and 
concomitant medications since the last visit; provide locator and 


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basic menses information; receive pre- and post-test HIV 
counselling, contraceptive counselling and HIV/STI risk-reduction 
counselling (including provision of male and/or female condoms, 
should participants wish to receive them); undergo a physical 
examination as well as a pelvic examination; be tested for STIs, 
pregnancy and HIV; and may undergo safety laboratory 
assessments,  urine dipstick analysis (microscopy only if clinically 
indicated) and cervical sample collection for cytology (if no result 
is evident within the previous year, or abnormal at last cervical 
cytology). Samples will be collected for vaginal pH and vaginal 
flora testing. Contraception and STI treatment will be provided or 
participants will be referred, if needed.   Blood samples will be 
collected for storage, and will be tested retrospectively by HIV-1 
RNA PCR and HIV viral genotype resistance testing subsequent 
to confirmed HIV seroconversion. Blood and vaginal fluid samples 
may be collected for measurement of dapivirine concentrations. 
Returned rings will be visually inspected by research centre staff 
and may also be analysed for residual amounts of dapivirine. 
Returned diary cards will be reviewed. Participants will be asked 
to complete a Participant Questionnaire. Ring use related 
questions will not be collected from Ring Non-users. 
 
 
Exit visit - approximately 1-2 months after ring discontinuation:  
On the day of the scheduled exit visit, participants will return to the 
research centre to receive results from their STI testing and safety 
laboratory assessments performed at the last product use visit, if 
applicable, and receive treatment or referral as needed. AEs, 
concomitant medications and possible social harms will be 
recorded at this visit. 
 
Participants will receive pre- and post-test counselling for HIV and 
undergo HIV testing. HIV/STI risk reduction counselling (including 
provision of male and/or female condoms, should they wish to 
receive them) and contraceptive counselling will also be provided 
at the exit visit. Contraception and STI treatment will be provided 
or the participant will be referred, if needed. The following 
procedures are not required, but may be conducted if clinically 
indicated: physical and pelvic examination, cervicovaginal sample 
collection for STI testing, provision of treatment and/or referral for 
STIs and other findings, laboratory testing for safety assessments, 
urine dipstick analysis (microscopy only if clinically indicated), and 
cervical sample collection for cytology (if no result is evident within 
the previous year, or abnormal at last cervical cytology). Blood 
samples will be collected for storage, and will be tested 
retrospectively by HIV-1 RNA PCR and HIV viral genotype 
resistance testing subsequent to confirmed HIV seroconversion. 
 
Participants will then be considered to have completed trial 
participation. 
 


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Qualitative and Quantitative Behavioural Assessments: 
Each research centre will conduct two to three in-depth individual 
interviews (IDIs) with approximately six participants in each of the 
following categories:  
 
Decliner Population  
 
Ring Users 
 
Ring Non-users 
 
In cases of interest IDIs will be conducted; approximately three 
participants will be interviewed per site. These cases of interest 
may include, but will not be limited to participants who may have 
experienced social harms, may have had problems using the ring, 
or who HIV seroconverted. 
 
Focus group discussions may be conducted with the above 
mentioned groups. Efforts will be made to ensure the sample size 
is representative of both previous IPM 027 participants as well as 
the two ring-naïve cohorts of women. Additionally, IDIs and/or 
FGDs with approximately six males from the community and/or 
male partners will be conducted at each research centre.  
 
DVR-naïve participants will complete a behavioural questionnaire 
at enrolment, in addition to the participant questionnaire collected 
at other trial visits. 
 
These assessments will provide data on acceptability and 
influencers of ring use. The recruitment and sampling strategy will 
be specified in the study operations manual. 
 
 
STATISTICAL CONSIDERATIONS: 
Sample Size:  
This is an open-label, follow-on trial to IPM 027 to evaluate the 
safety of and adherence to Dapivirine Vaginal Ring-004, inserted 
at monthly intervals in healthy, HIV-negative women who have 
participated in the IPM 027 trial and two additional cohorts of 
DVR-naïve young women. No formal sample size or power 
calculations have been performed. 
 
It is expected that up to 70% of the participants enrolled in 
IPM 027 will participate in this trial (up to 1400 HIV-negative 
women is anticipated). Two additional cohorts of healthy women 
aged ≥18 to ≤21 and >21 to <25 years, who have not used the 
Dapivirine Vaginal Ring-004 previously (DVR-naïve Cohorts), will 
be enrolled. Approximately 300 participants will be enrolled in 
each of these two additional cohorts. Total estimated enrollment in 
the trial will be approximately 2000 participants.      
 
Statistical Analyses:  
The primary analysis will focus on safety as well as adherence 
assessments, performed under the intent-to-treat (ITT) principle. 


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As it is possible that the inclusion of non-adherent participants or 
participants who discontinued from ring use may artificially lower 
the rates of safety outcomes, additional analyses will be 
conducted on the per-protocol population, which will include only 
participants who were adherent to the protocol. 
 
Primary, secondary and exploratory analyses will be conducted 
comparing the following groups of participants: 
 
Former IPM 027 participant ring users; ring non-users will 
be included in safety comparison 
 
The total of the DVR-naïve women (All) 
 
The two cohorts of DVR-naïve women  
   
A descriptive analysis of all AEs will be presented in tables and 
listings. AEs will be summarised by MedDRA System Organ Class 
(SOC) and Preferred Term (PT). The proportion of participants 
experiencing adverse events, including the proportion of 
participants experiencing product-related adverse events, Grade 3 
or 4 AEs, or SAEs, will be determined. The difference in incidence 
between the relevant groups of participants and the corresponding 
95% confidence intervals will be presented. The confidence 
intervals will be determined based on linear regression with robust 
standard errors, with research centre as covariate. In addition, AE 
dot plots will be prepared to graphically display the difference in 
incidence rates. 
 
Residual levels of dapivirine in returned rings, and/or plasma 
and/or vaginal fluid concentrations of dapivirine will be used as 
measures of adherence to ring use. The data will be listed, 
summarised and presented graphically for the two cohorts. The 
ring 
residual 
levels 
and/or 
plasma 
and/or 
vaginal 
fluid 
concentrations of dapivirine associated with non-adherence will be 
informed by the results from IPM 027, and will be described in 
detail in the SAP, which will be finalised prior to final database 
lock.  The correlation between the amount of residual dapivirine in 
the used rings and the corresponding plasma and/or vaginal fluid 
levels of dapivirine will be explored graphically and summarised 
descriptively.  
 
For the secondary analysis, the number of HIV-1 seroconversions, 
the incidence density rate of HIV-1 seroconversion, i.e. HIV-1 
seroconversion rate per 100 woman-years of product use at the 
end of the ring use period, as well as a 95% confidence interval for 
the HIV-1 seroconversion rate per 100 woman-years based on the 
normal approximation of the Poisson distribution will be presented 
for each cohort within research centre and per cohort overall 
across research centres. Kaplan-Meier curves will also be 
presented similarly. The analysis of HIV-1 drug resistance will be 
primarily descriptive in nature, and will depend on the pattern of 
resistance mutations observed in the HIV-1 seroconverters.  A 
frequency tabulation of individual resistance mutations associated 


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with the various classes of antiretrovirals, e.g. Protease Inhibitors, 
Nucleoside Reverse Transcriptase Inhibitors and Non-nucleoside 
Reverse Transcriptase Inhibitors, will be produced. The proportion 
of HIV-1 seroconverters with at least one HIV-1 drug resistant 
mutation will be presented per cohort within research centre, and 
per cohort overall across research centres, with the corresponding 
95% CI.  
 
Appropriate statistical analyses of the exploratory endpoints will be 
performed. 
 
 
 
 
Full details of the planned statistical analyses will be provided in a  
 
 
 
Statistical Analysis Plan (SAP) that will be finalised before final  
 
 
 
database lock. 
 
 
 
 
 


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1. Introduction 
1.1. Background 
Women continue to be affected disproportionately by HIV in sub-Saharan Africa, where 
they account for 58% of people living with HIV3. It is estimated that every hour, 50 young 
women are newly infected with HIV4. Unprotected heterosexual intercourse is currently 
the leading mode of HIV acquisition among women. Physiologically, women are more 
likely than men to acquire HIV during heterosexual intercourse, and young girls are most 
vulnerable5. In sub-Saharan Africa, the number of new HIV infections among adolescent 
girls and young women aged 15-24 years remains exceptionally high, with approximately 
8600 new infections per week6. These females are at least twice as likely to be infected 
with HIV as their male peers7. The United Nations (UN) Political Declaration on Ending 
AIDS adopted in June 2016 calls for reducing new HIV infections among adolescent girls 
and young women aged 15-24 years to fewer than 100,000 per year by 20208. Achieving 
this target demands dramatic acceleration of action and expanding of programs for 
adolescent girls and young women, as gender inequities often render women unable to 
abstain from sex or negotiate condom use with partners, a proven method of preventing 
HIV acquisition. Most current HIV prevention methods require the consent (as well as 
some action or behaviour change) of the male partner9. Therefore, the ongoing 
development of safe and effective HIV prevention technologies that can be made easily 
accessible to developing countries remains a public health priority.  
 
Developing HIV prevention options that women can use therefore remains a global 
challenge. Antiretroviral (ARV) approaches to prevention have the potential to transform 
the response to the HIV/AIDS pandemic. For women, further research is needed on 
microbicides that contain different ARV compounds in different formulations and dosing 
strategies, in order to provide various options for HIV prevention. Vaginal microbicides, 
which are self-initiated, could offer women a critically needed new tool to prevent HIV, 
especially for those women who are not able to negotiate mutual monogamy or condom 
use10. ARV-based microbicides can be formulated in a number of dosage forms that 
allow them to be used in a variety of ways, such as around the time of sex, or daily or 
monthly, independent of sexual activity.  
 
In order for a microbicide to be most effective, it is essential that it is used correctly and 
consistently, and is acceptable to women and their male partners. A product used 
independently of sexual intercourse could be more convenient for women and provide 
long-term protection during anticipated and unanticipated sexual intercourse. Vaginal 
rings that need monthly replacement may therefore have benefits. The Dapivirine 
Vaginal Ring-004 has completed Phase III clinical development.   
 
The results from two Phase III trials of the Dapivirine Vaginal Ring-004, The Ring Study 
(IPM 027) and ASPIRE (MTN- 020) were announced at the Conference on Retroviruses 
and Opportunistic Infections (CROI in Boston, MA) in February 2016. Both trials 
demonstrated that the Dapivirine Vaginal Ring-004 was safe and prevented HIV-1 
infection in approximately one in three women between the age of 18-45 years overall, a 
statistically significant result (p<0.05 in both trials1,2,11,12). Post-hoc data analyses provide 
supportive evidence that Dapivirine Vaginal Ring-004 protection against HIV-1 increases 
when adherence increases. The ASPIRE trial showed that women who appeared to use 
the ring more consistently (defined as at least 3 mg of dapivirine released from the ring 


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during 4 weeks of continuous use) had at least a 65% reduction in risk, and additional 
subgroup analyses of women who appeared to use the ring most consistently suggest 
75% or more reduction in risk13. Similarly, in a post-hoc analysis of The Ring Study data, 
65% efficacy was seen in women who appeared to use the Dapivirine Vaginal Ring-004 
more consistently11. A lower HIV-1 risk reduction was observed in women ≤21 years of 
age in IPM 027 (the age effect was not statistically significant). In ASPIRE, age was 
shown to be significantly related to HIV-1 protection, with no protection observed in 
participants aged 18-21 years, and 56% protection in participants over 21 years of 
age2,12. Further research is needed to understand younger women’s unique challenges 
in using HIV prevention methods, as well as exploring dapivirine vaginal ring-use in the 
context of known safety and efficacy and if it would increase the HIV risk reduction  
demonstrated in the Phase III trials.  
1.2. Dapivirine Vaginal Ring 
1.2.1. Dapivirine 
Dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is a di-amino-
pyrimidine 
(DAPY) 
derivative 
with 
the 
chemical 
name 
4-[[4-[(2,4,6-
trimethylphenyl)amino]-2-pyrimidinyl]amino] benzonitrile. NNRTIs bind directly to the HIV 
reverse transcriptase (RT) enzyme, preventing viral replication. Dapivirine was originally 
developed by Janssen Research and Development (formerly Tibotec Pharmaceuticals) 
as an oral antiretroviral compound and was tested in Phase I and II clinical trials in more 
than 200 participants. Although first conceived as an oral therapeutic, dapivirine is a 
promising candidate for development as a topical microbicide due to its proven in vitro 
and in vivo efficacy and favourable safety profile as well as its physical and chemical 
properties. Dapivirine has potent activity against wild-type HIV-1 strains and strains 
harbouring different resistance-inducing mutations. Dapivirine’s antiretroviral profile is 
superior to that of earlier NNRTI class compounds such as nevirapine, delavirdine, and 
efavirenz. In vitro tests have shown that dapivirine is inactive against HIV-2 and has no 
efficacy against common sexually transmitted infections. Dapivirine is therefore not 
intended to protect against HIV-2 or other sexually transmitted infections, nor does it 
have any contraceptive properties.  
 
1.2.2. Formulation of a Silicone Elastomer Matrix ring containing 25  mg of  
 Dapivirine 
The dapivirine silicone elastomer vaginal matrix ring (Ring-004) is an off-white flexible 
ring containing 25 mg of dapivirine dispersed in a platinum-catalysed silicone matrix. The 
dimensions of the ring are 56 mm (outer diameter) and 7.7 mm (cross-sectional 
diameter). Details regarding the formulation and dimensions are provided in the 
Dapivirine Vaginal Ring-004 Investigator’s Brochure (IB)14. The dapivirine vaginal ring is 
designed to provide sustained release of dapivirine for a minimum of one month. 
 
1.3. Nonclinical Studies 
The potential of dapivirine as a microbicide for prevention of sexual transmission of HIV 
has been assessed in a variety of in vitro, ex vivo and in vivo models.  Furthermore, a 
comprehensive program of preclinical studies was used to evaluate the toxicity of 
dapivirine. The studies are described in the IB14. 


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Virology: 
The activity of dapivirine against wild-type HIV-1, African isolates of HIV-1 (including 
subtype C virus), and a panel of NNRTI-resistant viruses has been established using in 
vitro models, with EC50 values ranging from 0.3 ng/mL (0.9 nM) against laboratory 
isolates to < 33 ng/mL (< 100 nM) for HIV-1 isolates encoding one or more known 
NNRTI resistance mutations. The anti-HIV activity was also confirmed in an ex vivo 
model of human cervical explant cultures and in an in vivo humanized severe combined 
immunodeficient (hu-SCID) mouse model. 
 
Nonclinical safety pharmacology: 
In a series of preclinical safety pharmacology studies, dapivirine was generally devoid of 
adverse effects on overt behaviour, reflexes and other body functions. Although safety 
pharmacology studies revealed no cardiovascular effects, there was evidence of an 
increase in QT interval during the 4- and 6-month oral toxicity study in dogs. However, 
this was only seen at ≥ 30 mg/kg/day, at which Cmax and AUC values were respectively 
more than 3800 and 2500 times the values achieved in women following use of the 
Dapivirine Vaginal Ring-004. 
 
Nonclinical pharmacokinetics:  
Systemic exposure to dapivirine was low following vaginal administration of dapivirine 
gels to rabbits. Much higher systemic exposures were obtained in single dose oral and 
subcutaneous toxicity studies in mice and rats, and in repeat dose oral toxicity studies in 
rats, dogs and monkeys. The free fraction of dapivirine in plasma was 0.19-0.34% in the 
male rat, 0.18-0.39% in the female rat, 0.21–0.22% in the dog and 0.15% in man. In rats, 
tissue to plasma AUC0-24 ratios following a single oral dose were 11 in liver, 7-8 in lung, 
kidney and adrenals, about 4 in spleen and lymph nodes, and 2-3 in brain, heart and 
muscle. Plasma/tissue equilibrium was rapid, and there was no undue retention of 
dapivirine in tissues.  
 
For virtually all tissues, maximal concentrations after vaginal dosing were < 1% of those 
after oral dosing. Preliminary metabolism studies demonstrated the presence of free and 
conjugated metabolites in rats, dogs, monkeys and humans, but the molecular structures 
have not been elucidated. There was evidence of extensive cytochrome P450 
(particularly CYP3A4) mediated metabolism. 
 
Nonclinical toxicology:  
Dapivirine has been investigated in single and repeat dose toxicity studies, in a range of 
reproductive toxicity and mutagenicity studies, and in a carcinogenicity study. In vaginal 
studies in rabbits there were no significant local or systemic findings following repeat 
administration at up to 20 mg/mL for 14 days, up to 5 mg/mL for 13 weeks or up to 2 
mg/mL for 39 weeks, or in reproductive toxicity studies in rats and rabbits performed at 
concentrations up to 2 mg/mL (0.2%). In a 13-week study in sheep using Ring-004, there 
was no evidence of local or systemic toxicity. 
 
The no adverse effect level (NOAEL) in rats and dogs following oral administration was 
20 mg/kg/day. At higher dose levels, hepatotoxicity was observed in dogs and slight 
hematological and clinical chemistry changes were observed in rats. The NOAEL in oral 
reproductive toxicity studies in the rat was also 20 mg/kg/day, whereas in the rabbit no 
effects were seen at dosages up to 90 mg/kg/day. Dapivirine was considered to be non-
genotoxic. In the guinea pig, dapivirine (2 mg/mL) did not demonstrate any potential to 


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cause contact sensitization. No treatment-related neoplastic or non-neoplastic findings 
were seen in a vaginal carcinogenicity study in rats at concentrations up to 5 mg/mL. 
 
1.4. Clinical Trials 
Multiple clinical trials have evaluated the safety of dapivirine in different formulations. 
Below is a summary of the data collected through these studies. More detailed 
information is available in the Dapivirine Vaginal Ring-004 IB14.  
 
Across all clinical trials with multiple ring configurations in healthy participants, the 
dapivirine vaginal ring was generally safe and well tolerated. No drug-related serious 
adverse events (SAEs) have been reported to date and no trials were stopped for safety 
reasons. In completed trials of Dapivirine Ring-004, one participant assigned to 
Dapivirine Ring-004 required permanent discontinuation of the investigational product 
due to a non-serious adverse event considered by the investigator as possibly related to 
product use. This event, a Grade 2 (moderate intensity) generalized pruritus,  required 
action taken by the Investigator to discontinue IP use permanently as a direct result of 
the event. Three SAEs were reported in dapivirine ring users (Ring-004) and six SAEs in 
placebo ring users. 
 
The Phase III clinical development program for the Dapivirine Vaginal Ring-004 included 
two pivotal trials, IPM 027 and MTN-020, which evaluated long term safety and efficacy 
of Dapivirine Vaginal Ring-004 compared to a placebo vaginal ring in 4588 participants 
(2620 enrolled to the dapivirine ring and 1968 enrolled to the placebo ring). Both trials 
demonstrated the safety and clinical efficacy of the Dapivirine Vaginal Ring-004.  No 
safety concerns or clinically relevant differences in safety parameters were observed 
between treatment groups.  No SAEs were considered related to the use of dapivirine or 
placebo vaginal rings in either trial.     
 
1.4.1. Phase I and II 
To date, 27 Phase I and Phase I/II clinical trials of dapivirine have been completed: 8 
trials of dapivirine vaginal rings in 469 participants (298 using dapivirine rings and 183 
using placebo rings); 8 trials of dapivirine vaginal gel in 774 participants (491 using 
dapivirine gel and 283 using placebo gel); and 11 trials of oral dapivirine in which a total 
of 211 participants used oral dapivirine. Two Phase I clinical trials that evaluated a 
vaginal film formulation of dapivirine in 71 women have been conducted.  In addition, 
one Phase I clinical trial in male participants to assess the safety and tolerability of a 
dapivirine vaginal gel, following multiple topical penile exposures, was conducted in 48 
healthy, HIV-negative, adult males, 24 of whom were circumcised and 24 uncircumcised 
(MTN-012/IPM 010). The dapivirine gel formulation was well tolerated by the 
participants. No SAEs or discontinuations due to TEAEs were reported during this trial. 
 
Based on information in the current IB14, across all completed Dapivirine Ring-004 trials 
(IPM 024, IPM 013, IPM 015, IPM 028 and IPM 034), the most commonly occurring 
TEAEs that were documented in at least 5% of participants in dapivirine versus placebo 
treated participants (n=259 using dapivirine rings and n=160 using placebo rings, 
respectively) were metrorrhagia (29.7% vs 24.4%), headache (15.1% vs 11.9%), 
gynaecological chlamydia infection (8.5% vs 13.4%), vaginal candidiasis (8.1% vs 7.5%), 
urinary tract infection (6.9% vs 8.8%), vaginal discharge (6.6% vs 6.3%), upper 


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respiratory tract infection (5.8% vs 10.0%) and lower abdominal pain (5.4% vs 5.0%). 
 
 
 
Oral Dapivirine 
There have been 11 oral administration trials in which a total of 211 participants have 
been dosed with dapivirine. The maximum tolerated dose (MTD) established was 350 
mg for a single dose, and for multiple doses, 300 mg b.i.d. for 14 days. There were no 
deaths during the clinical trials of oral dapivirine, and no trials were stopped for safety 
reasons. A total of 10 participants stopped dapivirine treatment prior to trial completion 
for safety reasons, 6 of whom stopped due to a clear dose-dependent increase in central 
nervous system (CNS) and gastrointestinal TEAEs, thereby establishing the MTD at 300 
mg b.i.d. These TEAEs resolved within 1-2 days after discontinuation of use of oral 
dapivirine.  
 
Adverse events documented in 5 or more participants (> 2%) after oral exposure to 
dapivirine were headache, dizziness, nausea, diarrhoea, fatigue, tremor, somnolence, 
flatulence, and vomiting. Most (≥ 80%) of these TEAEs were Grade 1 or 2 (mild or 
moderate) and most (≥ 80%) were considered to be related to dapivirine. Grade 3 
(severe) TEAEs included headache, dizziness, injury, nausea, tremor, paraesthesia, 
disturbance in attention, abrasion, AST increased, ALT increased, polyuria, fever, 
diarrhoea, and vomiting. The increases in AST and ALT were transient and the Grade 3 
increases in AST and ALT occurred in a single participant who received 50 mg oral 
dapivirine as a twice daily dose.  
 
1.4.2. Phase III  
The Phase III clinical program of the dapivirine vaginal ring, containing 25 mg of 
dapivirine (Ring-004), consisted of the MTN-020 and IPM 027 clinical trials. These trials 
were conducted in South Africa, Uganda, Zimbabwe and Malawi, to assess the safety 
and efficacy of the Dapivirine Vaginal Ring-004 in preventing the acquisition of HIV-1 
infection through male to female transmission in healthy, HIV-negative women.  
 
IPM 027 was a double-blind, multi-centre, placebo-controlled trial that was designed to 
assess the safety and efficacy of the Dapivirine Vaginal Ring-004, inserted once every 4 
weeks over a period of 24 months, in healthy, sexually active HIV-negative women, 18 to 
45 years of age, when compared to a placebo vaginal ring. It was conducted at 7 
research centres, six in South Africa and one in Uganda. A total of 1959 eligible women 
were randomized in a 2:1 ratio to receive either the dapivirine vaginal ring or placebo 
vaginal ring. Of these, 1307 women were enrolled in the dapivirine ring group and 652 
women in the placebo ring group. This trial was initiated in March 2012.  In November 
2015 the DSMB recommended a final early analysis of data.   
 
MTN-020 was designed to assess the safety and effectiveness of the Dapivirine Vaginal 
Ring-004, inserted once every 4 weeks, in healthy, sexually active, HIV-negative women, 
18 to 45 years of age, when compared to a placebo vaginal ring. It was conducted in 
Malawi, South Africa, Uganda and Zimbabwe. A total of 2629 women were randomized. 
Each participant was to use the investigational product until 120 events (HIV-1 
seroconversions) were observed in the trial. All participants were to use the 
investigational product for a minimum of 12 months. The trial was initiated in August 
2012 and clinical conduct completed in June 2015.  


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The results from two Phase III trials of the Dapivirine Vaginal Ring-004, The Ring Study 
(IPM 027) and ASPIRE (MTN- 020) were announced at the Conference on Retroviruses 
and Opportunistic Infections (CROI in Boston, MA) in February 2016. Both trials 
demonstrated that the Dapivirine Vaginal Ring-004 was safe and prevented HIV-1 
infection in approximately one in three women between the age of 18-45 years overall, a 
statistically significant result (p<0.05 in both trials1,2,11,12). Post-hoc data analyses provide 
supportive evidence that Dapivirine Vaginal Ring-004 protection against HIV-1 increases 
when adherence increases. The ASPIRE trial showed that women who appeared to use 
the ring more consistently (defined as at least 3 mg of dapivirine released from the ring 
during 4 weeks of continuous use) had at least a 65% reduction in risk, and additional 
subgroup analyses of women who appeared to use the ring most consistently suggest 
75% or more reduction in risk13. Similarly, in a post-hoc analysis of The Ring Study data, 
65% efficacy was seen in women who appeared to use the Dapivirine Vaginal Ring-004 
more consistently11. A lower HIV-1 risk reduction was observed in women ≤21 years of 
age in IPM 027 (the age effect was not statistically significant). In ASPIRE, age was 
shown to be significantly related to HIV-1 protection, with no protection observed in 
participants aged 18-21 years, and 56% protection in participants over 21 years of 
age2,12.  
 
 
1.4.3. Adherence to and Acceptability of the Dapivirine Vaginal Ring 
IPM 011 was an open-label, crossover trial conducted in South Africa and Tanzania 
among sexually active women to assess the safety and acceptability of a silicone 
elastomer placebo vaginal ring (containing no active ingredient), intended as a 
microbicide delivery method for the prevention of HIV infection. Participants were 
randomly assigned in a 1:1 ratio to one of two trial groups. Both groups participated in 
two regimens: a placebo vaginal ring regimen and an observational safety regimen (with 
no placebo vaginal ring). Each regimen had 12-week duration. Eighty-two percent (82%) 
of women in this trial reported no ring removals at all for the entire duration of the trial, 
across trial groups and visits, and 99% of participants reported wearing the ring for at 
least 80% of the days they were meant to. Eighteen percent (18%) of women self-
reported at least one ring removal or expulsion during the course of trial participation. 
This proportion increased to 22% when pharmacy records were incorporated. Many of 
the reported expulsions and removals were related to menses, e.g. heavy blood flow or 
concern about the ring becoming dirty or retaining odour, leading to removal. Ninety-five 
percent (95%) of women found the ring to be very comfortable. All questionnaire 
responders were willing to use the vaginal ring if shown to be effective for HIV 
prevention15. 
 
IPM 015 was a Phase I/II randomized, double-blind, placebo-controlled trial conducted at 
10 research centres in Kenya, Malawi, Tanzania and South Africa. The trial was 
performed in 280 HIV-negative, sexually active women, 18 to 40 years of age, to assess 
and compare the safety of 28-day use of Dapivirine Vaginal Ring-004, and a placebo 
vaginal ring, containing no dapivirine. Eligible women were randomly assigned in a 1:1 
ratio to the dapivirine ring or placebo ring,  inserted once every 28 days over a 12-week 
period.  In IPM 015, “perfect adherence” was reported by 92% of the female participants.  
Perfect adherence was defined as never having the ring out for more than an entire day. 
The most frequent activity associated with ring expulsion was urination/defecation and 
the most common reason reported by participants for removing the ring themselves was 
cleaning.  At the end of the trial, 96% of participants reported that the ring was usually 


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comfortable to wear, and 97% reported that they would be willing to use it in the future if 
it were proven effective and they thought they were at risk for HIV infection. Just over 
60% of the participants in both arms reported that their male partners did not feel the ring 
at Visit 5 (study week 12). A further 22% reported that their partner felt the ring during 
sex, but that it was not a problem. Only a small number (3%) at Visit 3 (study week 4) 
and (1%) at Visit 5 (study week 12) reported that her male partner felt the ring and it 
might be, or definitely was a problem for her to continue ring use16. 
 
 
1.4.4. Condom Compatibility 
Two clinical condom functionality studies (one with male condoms [IPM 029] and one 
with female condoms [IPM 033]) were conducted with a placebo vaginal ring 
(silicone elastomer ring containing no active ingredient). Results from both studies 
showed that the difference between the total clinical failure rate between condom 
use with the vaginal ring and condom use without the vaginal ring was less than the 
pre-defined non-inferiority margins (3% for the male condom study and 8% for the 
female condom study). Condom use was safe and well tolerated with vaginal ring 
use.  
 
Studies with dapivirine-containing vaginal gel formulations (0.05%, 2.5 g) were 
conducted on the following types of male and female condoms: 
 
Non-lubricated latex condoms (male condom) 
 
Silicone lubricated latex condoms (male and female condoms) 
 
Aqueous lubricated latex condoms (male condom) 
 
Polyurethane condoms with silicone lubricant (male and female condoms) 
 
Nitrile condoms with silicone lubricant (female condom) 
 
All types of condoms met the acceptance criteria established in the protocol for the mean 
values of the treated samples after treatment with dapivirine gels. The results of condom 
compatibility testing indicate that dapivirine-containing vaginal gel formulations (0.05%, 
2.5 g) have no deleterious effects on the integrity of male or female condoms14. 
 
1.5. Rationale for Protocol IPM 032 
The potential of dapivirine as a safe and efficacious microbicide for prevention of sexual 
transmission of HIV-1 has been evaluated in nonclinical studies (virology studies, 
secondary/safety pharmacology, pharmacokinetics, toxicology) using different in vitro, ex 
vivo and in vivo models, as well as Phase I-III clinical trials.  Results were communicated 
to the relevant local and international regulatory authorities, IRBs/IECs, community 
representatives, participants and key stakeholders, as appropriate, before activation of 
IPM 032. IPM is pursuing regulatory approval for the product.  
 
IPM 032, a Phase IIIb follow-on trial to IPM 027, has been designed as an open-label 
clinical trial to collect additional safety data and establish adherence to ring use of the 
Dapivirine Vaginal Ring-004 in healthy, HIV-negative women with monthly visits (up to a 
maximum of three monthly visit) followed by 3-monthly research centre follow-up visits 
over 12 months. Further, IPM 032 will examine incidence of HIV-1 seroconversion and 


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monitor HIV-1 resistance in women who acquire HIV-1 infection. The assessment of the 
monthly visits (first one to three months) followed by 3-monthly research centre follow-up 
visits will provide insight into the feasibility of a 3-monthly scheduling strategy that would 
be less costly and time-consuming in a resource-limited environment such as sub-
Saharan Africa.  
 
In light of the limited protection observed in younger women in IPM 027 and MTN-020, 
two additional cohorts of young women aged ≥18 to ≤21 years and >21 to <25 years, 
who have not used the Dapivirine Vaginal Ring-004 previously, will be included in the 
trial. These additional cohorts will provide additional data to gain a better understanding 
of younger women’s unique challenges in using HIV prevention methods. IPM 032 will 
collect behavioural data needed to support the potential introduction of a microbicide as 
a public health intervention and to assist with future program development, including 
reasons for IPM 027 participants’ decision to not enroll in IPM 032.  
2. Trial Objectives 
Primary, secondary and exploratory objectives will compare data between former IPM 
027 participants and DVR-naïve cohorts. The analysis will be described in the Statistical 
Analysis Plan. 
2.1. Trial Objectives 
The primary trial objectives are: 
1. To assess the safety profile of the 25 mg Dapivirine Vaginal Ring-004, when 
inserted at monthly intervals, in an open-label trial  
2. To assess adherence to the use of the 25 mg Dapivirine Vaginal Ring-004 
inserted at monthly intervals, in an open-label trial  
 
The secondary trial objectives are: 
1. To assess the incidence of HIV-1 seroconversion 
2. To assess the frequency of HIV-1 drug resistance in women who acquire HIV-1 
infection 
 
The exploratory trial objectives are: 
1. To assess the feasibility of 3-monthly follow-up visits, as a possible schedule for 
post-licensure vaginal ring clinical follow-up 
2. To explore the correlation between drug concentrations and results from the 
visual inspection of the returned vaginal rings by research staff between the 
monthly and 3-monthly research centre follow-up schedules 
3. To determine the proportion of participants  electing to undergo HIV rapid tests at 
the research centres between scheduled 3-monthly visits 
4. To characterize the IPM 027 participants who decline enrollment into IPM 032 
(Decliner Population) 
5. To explore self-reported acceptability of and adherence to the 25 mg Dapivirine 
Vaginal Ring-004.  


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2.2. Trial Endpoints and Assessments 
The primary endpoints are: 
1. Safety  
 
All Adverse Events (AEs) assessed by the investigator to be related to the 
Dapivirine Vaginal Ring-004 
 
All Grade 3 and 4 AEs 
 
All Serious Adverse Events (SAEs) 
 
2. Adherence 
 
Residual amounts of dapivirine in returned rings; and/or dapivirine 
concentrations in plasma and/or dapivirine concentrations in vaginal fluid  
 
The primary endpoints will be assessed through: 
1. Safety  
 
All product-related AEs, Grade 3 or 4 AEs, SAEs, physical examination, 
gynaecological 
assessments, 
including 
pelvic/speculum 
examination, 
laboratory tests and other indicated investigations 
2. Adherence 
 
Determined dapivirine residual amounts in returned used vaginal rings and/or 
 
Measured concentrations of dapivirine in plasma and/or 
 
Measured concentrations of dapivirine in vaginal fluids 
 
The secondary endpoints are: 
 
The HIV-1 seroconversion rate per 100 woman-years of product use at the 
end of the vaginal ring use period 
 
HIV-1 drug resistance mutations among participants who acquire HIV-1 
infection 
The secondary endpoints will be assessed through: 
 
Rapid and specialised laboratory testing according to a pre-specified HIV 
testing algorithm 
 
Viral genotype resistance testing methods which include sensitive methods to 
detect low frequency drug-resistant variants 
 
 
The exploratory endpoints are: 
 
Feasibility of 3-monthly clinical follow-up schedule 
 
Dapivirine residual amounts in returned used vaginal rings and/or dapivirine 
concentrations in blood and/or vaginal fluid in correlation with results from the 
visual inspection of the returned used vaginal rings by research staff 
 
Proportion of participants opting for HIV rapid tests at the research centre 
between scheduled 3-monthly research centre follow-up visits 


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 
Characteristics of IPM 027 participants who decline enrollment into IPM 032 
(Decliner Population) and reasons for declining 
 
The proportion of women who report the use of the vaginal ring as acceptable 
 
Participant self-reported patterns of ring use 
 
The exploratory endpoints will be assessed through: 
 
Participant report of feasibility regarding a 3-monthly clinical follow-up 
schedule (Participant Questionnaire) 
 
Number of women opting not to receive two additional rings at the 3-monthly 
visits 
 
Proportion of returned rings (used and unused) during the 3-monthly clinical 
follow-up schedule 
 
Dapivirine residual amounts in returned used vaginal rings and/or dapivirine 
concentrations in blood and/or vaginal fluid 
 
Visual inspection of the returned used vaginal rings by research centre staff 
 
Number of participants undergoing HIV rapid tests at the research centres 
between scheduled 3-monthly research centre follow-up visits 
 
Questionnaires and qualitative data regarding reasons for declining 
participation, ring acceptability and self-reported patterns of ring use.   
3. Overall Trial Design 
3.1. Trial Design 
IPM 032 is a Phase IIIb, multi-centre follow-on open-label trial to evaluate the continued 
adherence to and safety of the Dapivirine Vaginal Ring-004, inserted at monthly intervals 
in healthy, HIV-negative women who have participated in the IPM 027 Phase III 
Dapivirine Vaginal Ring-004 trial and two additional cohorts of ring-naïve young women. 
All women who have participated in IPM 027 and are HIV-negative at screening for IPM 
032 will be eligible. An estimate of up to 1400 former IPM 027 participants will be 
enrolled. Two additional cohorts of women aged ≥ 18 to ≤ 21 years and >21 to < 25 
years, who have not used the Dapivirine Vaginal Ring-004 previously (DVR-naïve 
Cohorts), will be enrolled. An estimated 300 participants will be enrolled in each of these 
two additional cohorts. Total estimated enrollment in the trial will be approximately 2000 
participants. All participants will receive the dapivirine vaginal ring containing 25 mg 
dapivirine (Ring-004) at enrolment and will attend a research centre follow-up visit one 
month after enrolment.  Following this visit, at investigator’s discretion, a participant can 
continue on a 3-monthly visit schedule. Monthly visits may however be extended up to 
the first three months of participation. Once the 3-monthly trial visit schedule 
commences, three rings will be dispensed. One ring will be self-inserted at the research 
centre and two additional rings will be dispensed for the participant to take home, or 
dispensing will take place as arranged with the participant. At any point following the first 
3 months of trial participation, participants may opt to continue using the ring (Ring 
Users) or to not use the ring (Ring Non-users) while continuing in the trial. Ring Non-
users may initiate continuous use of the ring again at any stage during their trial 
participation.      
 


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3.2. Trial Duration 
Each participant will engage in the screening process for up to 45 days prior to 
enrolment and will use the Dapivirine Vaginal Ring-004 for a period of up to 12 months. 
IPM will have the option to extend this trial period. Accrual will remain open for the 
duration of the trial conduct; therefore some participants may have a shortened duration 
of trial participation. 
 
Each participant will have an exit visit approximately 1-2 months after ring 
discontinuation, to assess safety and identify HIV seroconversions after product 
discontinuation.   
 
3.3. Trial Population 
Approximately 2000 HIV-negative women who understand the trial and can provide 
informed consent are expected to enrol in this open-label trial. This includes up to 1400 
women who participated in the IPM 027 Phase III Dapivirine Vaginal Ring-004 trial and 
two additional cohorts of approximately 300 women each, aged ≥18 to ≤21 years and 
>21 to <25 years respectively, who have not used the Dapivirine Vaginal Ring-004 
previously (DVR-naïve Cohorts). 
 
3.3.1. Inclusion Criteria – Women who Previously Enrolled in IPM 027 
Women must meet all the following criteria to be eligible to enrol in the trial: 
 
1. Previously enrolled in the IPM 027 trial 
2. Available for all visits and consent to follow all procedures scheduled for the trial 
3. Using an effective method of contraception at the Enrolment Visit, and intending 
to use an effective contraceptive method for the duration of trial participation, 
unless postmenopausal with no history of menses for one year prior to screening   
4. HIV-negative as determined by the HIV algorithm applied at Screening/Pre-
Enrolment 
5. Willing to refrain from participation in another research trial using drugs, vaccines, 
medical devices and microbicides for the duration of the IPM 032 trial 
6. Willing to provide adequate locator information for trial retention purposes and be 
reachable per local standard procedures (e.g., by home visit or telephone; or via 
family or close neighbour contacts); confidentiality to be maintained 
 
3.3.2. Exclusion Criteria – Women who Previously Enrolled in IPM 027 
Women who meet any of the following criteria are NOT eligible to enrol in the trial: 
 
1. Investigational product use permanently discontinued in response to an AE 
(where the AE was considered related to investigational product) or safety-related 
concern while taking part in the IPM 027 trial  
2. Currently pregnant, intends to become pregnant or currently breast-feeding 
3. Known drug abuse or alcohol dependence in the 12 months prior to screening 


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4. Participated in another research trial (other than IPM 027) using drugs, medical 
devices, microbicides or oral pre-exposure prophylaxis agents within 30 days prior 
to screening 
5. Any new illness or condition(s), chronic condition(s) or abnormal laboratory 
finding(s) that, in the opinion of the investigator, might put the participant at risk, or 
interfere with the trial objectives or the participant’s adherence to trial 
requirements 
 
3.3.3. Inclusion Criteria – DVR-naïve Cohorts: 
Women must meet all of the following criteria to be eligible for trial enrolment: 
 
1. Healthy women ≥18 and < 25 years of age, at screening, who can provide written 
informed consent  
2. Have not used the Dapivirine Vaginal Ring-004 previously 
3. Self-reported sexually active (defined as an average of at least one penetrative 
penile-vaginal coital act per month for the last 3 months prior to screening) 
4. Available for all visits and consent to follow all procedures scheduled for the trial 
5. Using an effective method of contraception at the Enrolment Visit, and intending 
to use an effective contraceptive method for the duration of trial participation 
unless surgically sterilised 
6. HIV-negative as determined by the HIV algorithm applied at Screening/Pre-
Enrolment 
7. Willing to refrain from participation in another research trial using drugs, vaccines, 
medical devices and microbicides for the duration of the IPM 032 trial 
8. Willing to provide adequate locator information for trial retention purposes and be 
reachable per local standard procedures (e.g. by home visit or telephone; or via 
family or close neighbour contacts); confidentiality to be maintained. 
 
3.3.4. Exclusion Criteria – DVR-naïve Cohorts: 
Women who meet any of the following criteria are NOT eligible to enrol in the trial: 
 
1. Currently pregnant or intends to become pregnant, or currently breast-feeding 
2. Known drug abuse or alcohol dependence in the 12 months prior to screening 
3. Participated in another research trial using drugs, vaccines, microbicides or 
medical devices within 30 days prior to screening 
4. Women with Grade 3 cervical cytology findings or Grade 3 intraepithelial 
neoplasia by biopsy (histology result) at screening  
5. Any history of anaphylaxis or severe allergy resulting in angioedema; or a history 
of sensitivity/allergy to latex or a silicone elastomer 
6. Any illness or condition(s), chronic condition(s) or abnormal laboratory finding(s) 
that, in the opinion of the investigator, might put the participant at risk, or interfere 
with the trial objectives or the participant’s adherence to trial requirements. 
 


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3.3.5. Inclusion Criteria – Decliner Population: 
Women must meet all of the following criteria to be eligible for Decliner Population 
behavioural assessments: 
 
1. Previously enrolled in IPM 027  
2. Eligible for screening in IPM 032 (i.e. HIV-negative at last IPM 027 trial visit, 
investigational product use NOT permanently discontinued in response to an AE 
(where the AE was considered related to the investigational product) or a safety-
related concern while taking part in the IPM 027 trial) 
3. Declines enrollment into IPM 032  
4. Able and willing to provide written informed consent  
5. Able and willing to perform decliner population behavioural assessments. 
 
4. Trial Visits and Procedures 
4.1. Pre-screening 
As part of participant outreach and recruitment strategies, study staff may pre-
screen potential trial participants either telephonically, on-site or at off-site locations. 
Study staff will explain the trial to potential participants and determine basic 
elements of eligibility which will be confirmed during the on-site screening visits. 
Interested participants will be scheduled for an on-site screening visit.  
 
Decliner Population:  
Previous IPM 027 participants who decline participation in IPM 032 will be asked to 
provide written informed consent to collect information on their reasons for declining 
participation. If they are willing to participate in the questionnaire interview, 
participants will be given the choice of meeting the interviewers at a convenient 
location off-site or at the research centre. Questionnaires may be completed 
telephonically after written informed consent has been obtained from the participant 
(refer to Section 5.17.3.)   
 
Reasons for declining participation will be captured in a decliner population 
questionnaire, and may be collected retrospectively. A decliner population ID (DP-
ID) will be assigned to each participant (Refer to Section 5.19). Written informed 
consent will be obtained from all participants in the decliner population to be 
contacted for participation in further behavioural assessments (e.g. qualitative in-
depth interviews [IDIs] and/or focus group discussion [FGD]), either on-site or at an 
off-site location. Written informed consent will be obtained prior to these IDIs and 
FGDs.  
4.2. Screening Visit  
NOTE: For potential participants who do not meet the eligibility criteria, screening 
procedures will be discontinued once ineligibility has been determined. Women who fail 
screening may be re-screened once and may be enrolled if they are found to meet ALL 
inclusion and NO exclusion criteria at the second screening visit.  


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In the event that the IPM 027 trial is stopped prematurely and IPM 032 is activated at the 
research centre, the IPM 027 LPUV and the IPM 032 Screening and Enrolment Visits 
may be combined for participants who are eligible to enrol in the IPM 032 trial. In these 
situations, a separate Screening visit will not be required, and only the procedures 
indicated in italics are required. 
 
a. Explain the screening, enrolment and trial procedures to the potential participant.  
b. If the potential participant agrees, obtain written informed consent. Illiterate 
participants may provide a thumbprint or mark witnessed and signed by a person 
independent from trial staff (refer to Section 5.1). A comprehension assessment 
checklist will be used to support the consent process (refer to Section 5.2).  
c. Assign a unique SCR-ID number to the potential participant (refer to section 
5.19).  
d. Conduct a review of inclusion/exclusion criteria with the potential participant.  
e. Collect demographic information from the potential participant.  
f. 
Obtain and record locator information.  
g. Record basic menses information, relevant medical history, and concomitant 
medication taken within the last 30 days (refer to Section 5.7 for more details 
about relevant medical history).  
h. Perform urine pregnancy testing. Refer pregnant women to local prenatal clinic 
for support services (refer to Section 5.6).  
i. 
Provide HIV/STI risk-reduction counselling (including provision of male and/or 
female condoms, should participants wish to receive them), contraceptive 
counselling and the provision of contraceptives, if necessary (refer to Sections 
5.3.2 and 5.5).  
j. 
Provide HIV pre- and post-test counselling (refer to Section 5.3.1).  
k. Perform HIV rapid testing as detailed in Section 5.4.1.  
l. 
Collect a blood specimen by venepuncture for storage for possible HIV viral 
genotype resistance and HIV-1 RNA PCR testing (Blood volume specified in 
Appendix C). 
m. Perform general physical examination (refer to Section 5.8 for a description of the 
elements required in the general physical examination).  
n. Perform a pelvic examination (refer to Section 5.9). If the pelvic examination 
indicates abnormal findings, e.g., any symptoms or evidence of genital infections, 
abrasions, ulcerations, etc., provide or refer for appropriate treatment.  
NOTE: If the participant is menstruating at this visit, the pelvic examination may 
be conducted as per investigator and participant discretion. If this is not possible, 
the participant will be asked to return 2 days after completion of menstruation.  
o. Collect cervicovaginal swabs for STI testing and a specimen for cervical cytology, 
if no result is evident within the previous year, or abnormal at last cervical 
cytology (refer to Sections 5.11.1 and 5.12). Women 
with 
Grade 
3 
cervical 
cytology findings or Grade 3 intraepithelial neoplasia by biopsy (histology result) 
at screening should be referred according to National guidelines 
p. Provide treatment and/or referral for STIs and other findings, as necessary (refer 
to Section 5.11.2). 


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q. Perform a urine dipstick analysis (microscopy only if clinically indicated). Collect 
blood samples by venepuncture for syphilis testing (RPR) and confirmatory test 
(if required), and the following safety laboratory tests (Blood volumes specified in 
Appendix C): haematology (FBC with differential and platelet count), and 
chemistry (creatinine, ALT, AST) (refer to Section 5.10).  
r. Other procedures, as clinically indicated and with prior approval from IPM. 
s. Schedule the Enrolment Visit within 45 days 
  
4.3. Enrolment Visit 
Note: The Enrolment Visit will occur within 45 days after the Screening Visit.  
 
In the event that the IPM 027 trial is stopped prematurely and the IPM 032 is activated at 
the research centre, the IPM 027 LPUV and the IPM 032 Screening and Enrolment Visits 
may be combined for participants who are eligible to enrol in IPM 032. Trial procedures 
conducted as part of the IPM 027 LPUV will not be repeated for the IPM 032 trial. Only 
the procedures indicated in italics are required. 
 
Pre-enrolment: 
a. Update locator, menses and pre-enrolment medical history information as 
necessary (refer to Section 5.7).  
b. Provide contraceptive counselling and contraceptives, if necessary (refer to 
Section 5.5).  
c. Provide HIV/STI risk reduction counselling, including provision of male and/or 
female condoms if the participant wishes to receive them (refer to Section 5.3.2).  
d. Record possible social harms (refer to Section 10.2)  
e. Obtain and record any concomitant medication information since the last visit.  
f. 
Perform urine pregnancy testing. Refer pregnant women to local prenatal clinic 
for support services (refer to Section 5.6).  
g. Provide HIV pre- and post-test counselling (refer to Section 5.3.1).  
h. Perform HIV rapid testing as detailed in Section 5.4.2.  
NOTE: Additional procedures for participants who test HIV-positive are also 
described in Section 5.4.2 of the protocol.  
i. 
Reassess and confirm eligibility. 
 
Post-enrolment: 
j. 
Assign a unique PID number to the participant (refer to Section 5.19).   
k. Collect a blood specimen by venepuncture for storage for possible HIV viral 
genotype resistance and HIV-1 RNA PCR testing (Blood volume specified in 
Appendix C). 
l. 
Collect 
specimen 
for 
assessment 
of 
vaginal 
pH 
and 
vaginal 
flora.  
NOTE: At the discretion of the investigator or designee, this specimen may be 
collected at the time of the screening pelvic examination. 
m. Obtain and record any AE information.  


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n. Provide adherence counselling, including adherence to trial visit schedule and 
requirements and vaginal ring adherence (refer to Section 5.15). Participants will 
be instructed to keep the ring inserted for a period of one month. Adherence 
counselling will include information on actions that should be taken in the event of 
expulsion or removal of the ring. If the ring comes out or is removed during this 
period, the participant should wash her hands, rinse the ring thoroughly in clean 
water and re-insert it.  
o. Provide and explain the use of the diary card to the participant (refer to Section 
5.20). 
p. Dispense one vaginal ring to each participant and provide vaginal ring use and 
storage instructions (refer to Sections 5.13 and 6.4). 
q. Instruct the participant to insert the vaginal ring (refer to Section 5.14). 
r. The following procedures are not required, but may be conducted if clinically 
indicated: physical and pelvic examination, cervicovaginal sample collection for 
STI testing, provision of treatment and/or referral for STIs and other findings, 
laboratory testing for safety assessments, urine dipstick analysis (microscopy 
only if clinically indicated) and cervical sample collection for cytology (if no result 
is evident within the previous year, or abnormal at last cervical cytology). 
s. For DVR-naïve Cohort participants only: complete a baseline behavioural 
questionnaire (refer to Section 5.17.2). 
t. 
Schedule the next visit. 
 
 
4.4. Trial Visits (Monthly research centre visits for the first one to three 
months, and 3-monthly research centre visits thereafter) 
Note: All visit dates will be calculated from the enrolment visit as baseline date. Each 
scheduled visit while the participant is on the IP has a window period of ± 7 days. 
 
a. Update locator and menses information as necessary.  
b. Obtain and record any AE and concomitant medication information since the last 
visit.  
c. Record possible social harms (refer to Section 10.2). 
d. Perform urine pregnancy test. Refer pregnant women to local prenatal clinic for 
support services (refer to Section 5.6).  
e. Provide HIV pre- and post-test counselling (refer to Section 5.3.1).  
f. 
Perform HIV rapid testing as detailed in Section 5.4.3.  
NOTE: Additional procedures for participants who test HIV-positive are also 
described in Section 5.4.3 of the protocol. 
g. Collect a blood specimen by venepuncture for storage for possible HIV viral 
genotype resistance and HIV-1 RNA PCR testing (Blood volume specified in 
Appendix C). 
h. Collect blood (Blood volume specified in Appendix C) and vaginal fluid samples 
(refer to Section 5.18) for possible measurement of dapivirine concentrations. 
NOTE: Not applicable to participants who opt not to use the ring at any point 


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following the first 3 months of participation. 
NOTE: For dapivirine concentration measurements, blood and vaginal fluid 
samples should preferably be collected prior to removal of the vaginal ring.   
i. 
Instruct the participant to remove the vaginal ring. Collect all used rings from 
participants. Perform IP accountability and visual inspection of the returned 
ring(s). Returned rings may be analysed for residual amounts of dapivirine and 
will be stored until shipment to the analytical laboratory. 
Dispense one vaginal ring to participants during monthly visits and three vaginal 
rings during 3-monthly visits (or dispense as arranged with the participant) and 
provide vaginal ring use and storage instructions (refer to Sections 5.13 and 6.4).  
At all follow-up visits following the first 3 months of trial participation, rings will be 
offered to all participants and dispensed as described above to participants who 
opt to use the ring. In the event that a non-user decides to start using the ring 
again between scheduled trial visits, ring(s) may be dispensed at an unscheduled 
visit, following confirmation of negative pregnancy and HIV test results. 
j. 
Instruct the participant to insert the vaginal ring during monthly visits.   Once the 
3-monthly trial visit schedule commences, one ring will be inserted at the 
research centre and two additional rings will be dispensed for the participant to 
take home (or dispense as arranged with the participant (refer to Section 5.14). 
NOTE: Not applicable to participants who opt not to use the ring at any point 
following the first 3 months of participation.  
k. Collect and review the diary card(s) and provide a new diary card(s) if applicable 
(refer to Section 5.20).  
l. 
Administer the Participant Questionnaire at every trial visit (refer to Section 
5.17.1). 
m. Provide adherence counselling, including adherence to trial visit schedule and 
requirements, and vaginal ring adherence (refer to Section 5.15). Participants will 
be instructed to keep the ring inserted for a period of one month. Adherence 
counselling will include information on actions that should be taken in the event of 
expulsion or removal. If the ring comes out or is removed during this period, the 
participant should wash her hands, rinse the ring thoroughly in clean water and 
re-insert 
it.  
NOTE: Not applicable to participants who opt not to use the ring at any point 
following the first 3 months of participation. 
n. Provide contraceptive counselling and contraceptives, if necessary (refer to 
Section 5.5).  
o. Provide HIV/STI risk reduction counselling; including provision of male and/or 
female condoms if the participant wishes to receive them (refer to Section 5.3.2).  
p. The following procedures are not required, but may be conducted if clinically 
indicated: physical and pelvic examination, cervicovaginal sample collection for 
STI testing, provision of treatment and/or referral for STIs and other findings, 
laboratory testing for safety assessments, urine dipstick analysis (microscopy 
only if clinically indicated) and cervical sample collection for cytology (if no result 
is evident within the previous year, or abnormal at last cervical cytology). 
q. Collect specimen for assessment of vaginal pH and vaginal flora. 
r. Schedule the next visit.  


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4.5. Last Product Use Visit (LPUV) or Early Discontinuation Visit  
Note: LPUVs will be calculated from the enrolment visit as baseline date. This scheduled 
visit has a window period of ± 7 days. 
 
a. Update locator and menses information as necessary.  
b. Obtain and record any AE and concomitant medication information since the last 
visit.  
c. Perform a pelvic examination (refer to Section 5.9). If the pelvic examination 
indicates abnormal findings, e.g., any symptoms or evidence of genital infections, 
abrasions, ulcerations, etc., provide the participant with or refer the participant for 
appropriate treatment.  
NOTE: If the participant is menstruating at this visit, the pelvic examination may 
be conducted as per investigator and participant discretion. If this is not possible, 
the participant will be asked to return 2 days after completion of menstruation.  
d. Record possible social harms (refer to Section 10.2)  
e. Perform a general physical examination (refer to Section 5.8 for a description of 
the elements required in the general physical examination).  
f. 
Instruct the participant to remove the vaginal ring. Perform IP accountability and 
visual inspection of the returned ring(s). Returned rings may be analysed for 
residual amounts of dapivirine and will be stored until shipment to the analytical 
laboratory.  
NOTE: Not applicable to participants who opt not to use the ring. 
g. Collect and review the diary card(s).  
h. Administer the Participant Questionnaire (refer to Section 5.17.1). 
i. 
Provide HIV/STI risk reduction counselling; including provision of male and/or 
female condoms if the participant wishes to receive them (refer to Section 5.3.2).  
j. 
Perform contraceptive counselling and provide contraceptives, if necessary (refer 
to Section 5.5).  
k. Perform urine pregnancy test. Refer pregnant women to local prenatal clinic for 
support services (refer to Section 5.6).  
l. 
Collect cervicovaginal swabs for STI testing (refer to Sections 5.11.1).  
m. Provide STI treatment if needed (refer to Section 5.11.2). 
n. Provide HIV pre- and post-test counselling (refer to Section 5.3.1).  
o. Perform HIV rapid testing as detailed in Section 5.4.3.  
p. Collect a blood specimen by venepuncture for storage for possible HIV viral 
genotype resistance and HIV-1 RNA PCR testing (Blood volume specified in 
Appendix C). 
q. Collect blood (Blood volume specified in Appendix C) and vaginal fluid samples 
(refer to Section 5.18) for possible measurement of dapivirine concentrations. 
NOTE: Not applicable to participants who opt not to use the ring. 
NOTE: For dapivirine concentration measurements, blood and vaginal fluid 
samples should preferably be collected prior to removal of the vaginal ring.   
r. The following procedures are not required, but may be conducted if clinically 


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indicated: laboratory testing for safety assessments, urine dipstick analysis 
(microscopy only if clinically indicated) and cervical sample collection for cytology 
(if no result is evident within the previous year, or abnormal at last cervical 
cytology).  
s. Collect specimen for assessment of vaginal pH and vaginal flora. 
t. 
Schedule the exit visit. 
 
4.6. Exit Visit 
Note: Exit Visits will occur approximately 1-2 months after ring discontinuation. Exit visits 
will be optional for Ring Non-users at the point of trial termination. If the outcome of 
confirmatory tests is pending, the exit visit may be conducted more than 2 months after 
the last product use visit, but should be performed as soon as possible after the results 
are available. Participants will be notified of any abnormal laboratory findings, and return 
to the research centre prior to the exit visit as needed for treatment and/or referral. 
Additional trial procedures for exit visits scheduled following HIV seroconversion are 
described in Section 5.4.4. 
 
a. Obtain and record any AE and concomitant medication information since the last 
visit.  
b. Record possible social harms (refer to Section 10.2). 
c. Perform contraceptive counselling and provide contraceptives, if necessary (refer 
to Section 5.5).  
d. Provide HIV/STI risk reduction counselling; including provision of male and/or 
female condoms if the participant wishes to receive them (refer to Section 5.3.2).  
e. Provide HIV pre- and post-test counselling (refer to Section 5.3.1).  
f. 
Perform HIV rapid testing as detailed in Section 5.4.4 (additional procedures for 
participants who test HIV-positive are also described in Section 5.4.4 of the 
protocol).  
g. Collect a blood specimen by venepuncture for storage for possible HIV viral 
genotype resistance and HIV-1 RNA PCR testing (Blood volume specified in 
Appendix C). 
h. Provide final safety and STI laboratory test results to participant.  
i. 
The following procedures are not required, but may be conducted if clinically 
indicated: physical and pelvic examination, cervicovaginal sample collection for 
STI testing, provision of treatment and/or referral for STIs and other findings, 
laboratory testing for safety assessments, urine dipstick analysis (microscopy 
only if clinically indicated) and cervical sample collection for cytology (if no result 
is evident within the previous year, or abnormal at last cervical cytology). 
j. 
Exit the participant from the trial.  
 
4.7. Unscheduled Visits 
Unscheduled visits may be performed at any time during the trial for HIV, STI or 
pregnancy testing, collection of ring(s), or if the participant is experiencing any problems, 


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e.g., vaginal complaints, difficulties with re-inserting the ring in cases of accidental 
expulsion or ring removal, accidental loss of the ring or product adherence challenges. 
Participants will also be notified of any abnormal laboratory findings, and return to the 
research centre prior to the next scheduled visit as needed for treatment and/or referral 
to an outside medical facility. Additional laboratory testing to evaluate AEs that are 
suspected to be associated with use of the IP may be performed where indicated, in 
consultation with the IPM Clinical Physician. 
 
All unscheduled visits will be documented in the source documents and applicable case 
report forms (CRFs). 
 
4.8. Missed and Late Visits 
Trial staff will make every effort to contact participants to return to the research centre for 
scheduled visits. If a participant does not return to the research centre for a scheduled 
visit during the trial window, e.g., within ± 7 days of a scheduled visit, continued attempts 
to contact the participant will be made as per local standard operating procedure (SOP) 
and documented in the source documents. 
 
If the participant does not return to the research centre for a scheduled visit prior to the 
start of the trial window of the next visit, the visit will be considered missed. For example, 
if a participant does not return for Visit 2 by the time the trial window has begun for Visit 
3, i.e., within 7 days from Visit 3, Visit 2 will be considered missed. Trial procedures will 
be performed as scheduled for the current visit (e.g. Visit 3 in this instance) or as 
deemed necessary by the investigator or IPM Clinical Physician (or designee). Missed 
visits will be documented as protocol deviations. Trial staff should ensure that all used or 
unused vaginal rings that were to be returned at the missed visit are retrieved as soon as 
possible. 
 
In the event that a participant will be away and unable to attend one of the Trial Visits 
where new vaginal rings would be dispensed, the investigator or designee could 
dispense additional ring(s) on a case-by-case basis. Research centre staff will enquire 
about adverse events and concomitant medication over the telephone; and other 
information will be collected as applicable.  
 
If a participant presents for a visit outside the window for a scheduled trial visit but prior 
to the start of the window for the next visit, it will be treated as a late visit and 
documented as a protocol deviation. All trial procedures scheduled for the late 
scheduled visit will still be performed. The participant will then resume her original visit 
schedule. 
 
If a LPUV is missed, STI testing should be performed at the Exit Visit. 
 
4.9. Protocol Deviations 
A protocol deviation is defined as any change, non-compliance or divergence from the 
approved protocol. The non-compliance may be either on the part of the participant, the 
investigator, the research centre staff or laboratory staff. It is the responsibility of the 
research centre to identify and report protocol deviations according to the guidelines of 


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the sponsor and the local IRB/IEC. The research centre must report protocol deviations 
to IPM using designated forms. The principal investigator and research centre staff are 
responsible for being familiar with and adhering to their IRB/IEC requirements. In 
response to noted protocol deviations, research centre personnel are to promptly 
implement corrective actions. 
 
4.10. 
Early Discontinuation Visits 
Participants may be discontinued early from the trial prior to completion of the last trial 
visit for any of the following reasons: 
 
Participant withdraws her consent. 
 
Participant is lost to follow-up, i.e., research centre is unsuccessful (following 
reasonable attempts as defined in the research centre SOP) in contacting 
participant or bringing the participant back to the research centre. 
 
Participant tests HIV-positive according to the HIV-testing algorithm in 
Appendix B.  
 
If, for safety reasons, the investigator considers it in the best interest of the 
participant to discontinue her from the trial.  
 
At the discretion of the investigator, Sponsor, IRB/IEC or the government 
health authority. 
The date and reason for permanent trial discontinuation will be noted in the source 
documents and applicable CRFs. All participants who are prematurely discontinued from 
the trial will be encouraged to return to the research centre for a final evaluation, at 
which time all trial procedures scheduled for the last product use visit will be performed. 
An optional exit visit approximately 1-2 months after product discontinuation can be 
completed. 
 
Participants who are considered lost to follow-up will be temporarily discontinued from 
the trial. Reasonable contact attempts will be made according to the locator information 
provided by the participant and local SOPs, and temporarily early trial termination will be 
documented in the source documents and applicable CRFs. If a participant already 
considered lost to follow-up returns to the research centre prior to the centre’s trial 
completion, the participant’s file (including CRFs) may be re-opened to perform trial 
discontinuation procedures. The participant may be considered for continuation on the 
trial at the discretion of the principal investigator in consultation with the IPM Clinical 
Project Manager, depending on the reason for the missed visits. A final trial termination 
will be documented in the source documents and applicable CRFs during the trial 
closure for all temporarily early trial terminations. 
 
4.11. 
Premature Discontinuation of the Trial 
IPM has the right to terminate this trial at any time for any reason. If the trial is 
prematurely terminated, the investigator must promptly inform the participants and the 
IRBs/IECs, and ensure proper medical follow-up of participants in consultation with IPM. 
If the trial is prematurely terminated, all procedures and requirements pertaining to the 
archiving of the trial documents will be observed. IPM will provide the research centres 
with instructions on the proper disposition of any clinical supplies at the centre.  


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5. Trial Procedure Details  
5.1. Informed Consent 
The informed consent documents will include all the information about the trial required 
by GCP and will make provision for the dated signatures of the participant, the principal 
investigator or designated trial staff conducting the informed consent process, and when 
required, also for a dated signature by an impartial witness. The informed consent 
process will be administered at the Screening Visit. 
 
The informed consent process will include adequate time for each potential participant to 
have any trial related questions answered by appropriately qualified and trained trial staff 
as designated by the investigator, and the entire process will be documented in the 
source documents. 
 
At screening, potential participants who agree to participate in the trial will sign and date 
the ICF. The ICF will also be signed and dated by the trial staff administering the consent 
process as delegated by the principal investigator according to the research centre SOP. 
If a potential participant is functionally illiterate, the informed consent document(s) and 
any written study-related materials must be read to her in the language best understood 
by the potential participant in the presence of an impartial literate witness. After the 
illiterate participant has orally consented to participate in the trial, and, if capable of 
doing so, has signed the ICF or provided a thumbprint or mark that was witnessed by the 
impartial witness, this impartial witness must sign and personally date the ICF. By 
signing the ICF the impartial witness attests that the information in the participant 
information sheet and any other written information was explained to, and apparently 
understood by, the participant or the participant’s legally acceptable representative and 
that informed consent was freely given by the participant or the participant’s legally 
acceptable representative. 
 
The signed and dated ICFs will be retained at the research centre. A copy of the signed 
and dated ICFs will be offered to the participant. If the participant is not willing to receive 
the documents, the second copy will be retained at the research centre. Likewise, during 
the trial, signed and dated ICF updates and any amendments to written trial-related 
materials to be given to participants will be offered to the participant but retained at the 
research centre if the participant is unwilling to receive the documents. Documentation of 
the participant’s refusal to accept a copy of the ICF(s) or other trial-related materials will 
be noted in the source documents.  
 
The consent documents and any trial-related materials given to the participant will be 
translated and back-translated in the local languages according to local IRB/IEC 
requirements and regulatory authority guidelines. Information in the informed consent 
documents and trial-related material will be verbally communicated by trial staff, in the 
language preferred by the participant, and copies of the documents and trial-related 
materials will be offered to her in her preferred language. Documentation will be required 
to verify who performed translation/back-translation of the materials as well as a written 
statement by the translator indicating that the consent form(s) is an accurate translation 
of the accompanying English version. This is the principal investigator’s responsibility. 
 
All research centre-specific informed consent documents will first be reviewed and 
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administration to the participants. 
 
If new information becomes available which may be relevant to the participant’s 
willingness to continue trial participation, the information will be provided via IRB and/or 
IEC-approved revised informed consent documents or addenda to the original informed 
consent documents in a timely manner and will be signed and dated by the participant in 
the same manner described above. 
 
Written informed consent will be obtained from all participants selected for participation 
in the IDIs, FGDs and Decliner Population Questionnaires.  
 
5.2. Comprehension Assessment Checklist  
Trial staff will assess the potential participant’s understanding of informed consent 
information prior to obtaining a signature on the ICF at the Screening Visit. This 
assessment will be done using a standardised comprehension assessment checklist. All 
comprehension problems that are discovered during the assessment will be discussed 
until staff member(s) are satisfied that the participant can verbalise her understanding of 
the issue. This process will be documented on the comprehension assessment checklist. 
This checklist will be recorded in source documentation at the research centre. A 
participant who cannot demonstrate comprehension of the informed consent information 
will not be enrolled in the trial. This process will not be applicable to decliner population 
participants.  
 
5.3. HIV Counselling 
5.3.1. HIV Pre-and post-Test Counselling 
At all visits where HIV testing is performed, pre- and post-test counselling will be 
provided according to the National Guidelines for HIV Counselling and Testing. 
Adaptations of these guidelines in accordance with locally accepted standards of 
practice are allowed. Each research centre will document the counselling policies and 
procedures prior to trial implementation for purposes of staff training, quality assurance, 
and trial monitoring. 
 
A comprehensive package of post-test counselling and psychosocial support will be 
provided to women who test HIV reactive at any point during trial participation. Initial 
counselling services will be provided at the research centre and women will be referred 
for additional counselling, support services and treatment. These services will be 
identified by the research centres prior to trial initiation and referral procedures will be 
documented in writing by the centre. 
 
5.3.2. HIV/STI Risk Reduction Counselling 
HIV/STI risk reduction counselling will be in accordance with local guidelines. 
Counselling will be provided at all research centre visits. Efforts will be made to ensure 
standardisation of risk reduction counselling at the trial research centres. 
 
NOTE: Risk reduction counselling will include recommendation of male condom use. 
Participants will be provided with a supply of male non-spermicidal condoms and/or 


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female condoms during each trial visit, if they are willing to accept them. The use of 
female condoms is permitted in this trial. 
 
5.4. HIV Testing and Management 
The research centres will inform IPM Medical Safety of any new HIV seroconversions 
within 48 hours of diagnosis. The applicable regulatory authorities and independent 
ethics committees who require expedited notification of HIV seroconversion will be 
notified by either IPM or the research centre in accordance with standard operating 
procedures and policies of the regulatory authorities or independent ethics committees. 
The details of the HIV rapid test kits will be specified in the Laboratory Manual, as part of 
the SOM. Participants will be tested for HIV using a highly sensitive antibody rapid test 
(Test 1) followed by a highly specific antibody test (Test2), if Test 1 is reactive. 
 
5.4.1. Screening Visit 
If the highly sensitive HIV antibody rapid test (Test 1) result is non-reactive, the 
participant could potentially be enrolled in the trial if she is otherwise eligible.  
 
If Test 1 is reactive at screening, a highly specific HIV antibody Rapid Test (Test 2) will 
be performed. If Test 2 is reactive, the potential participant is considered to be HIV 
seropositive and not eligible for enrolment. Initial counselling services will be provided at 
the research centre and the participant will be referred for additional counselling, support 
services and treatment. These referral systems will be implemented by research centres 
prior to trial start. It is the participant’s responsibility to follow up with relevant medical 
services once referral has been initiated by the research centre. 
 
If Test 1 and Test 2 yield discordant results the potential participant is considered to be 
potentially HIV-seronegative and can be given a date for enrolment into the trial. Refer to 
Appendix B: HIV Testing Algorithms. 
 
A blood sample will be obtained by venepuncture to be sent for sample storage locally or 
at a central laboratory, for potential HIV-1 RNA PCR and viral genotype resistance 
testing if the participant seroconverts (blood volume specified in Appendix C). Storage 
samples for participants who do not enrol will be destroyed according to research centre 
SOPs. 
 
NOTE: For the purposes of HIV rapid testing at screening, blood may be obtained by 
finger prick or venous sampling. If the national regulatory authority of the country in 
which the research centre is situated requires that a national testing algorithm be used 
during the screening process, this will be performed, in addition to the IPM 032 HIV 
testing algorithm, as part of the screening process and documented as such. 
 
5.4.2. Enrolment Visit 
On the scheduled day of possible enrolment, the participant will be tested for HIV and 
will only be enrolled if the results are considered to be HIV-seronegative and the 
participant is otherwise eligible.  
 
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history to suggest recent exposure that could be masked during the window period, the 
potential participant will be considered HIV-seronegative and eligible for enrolment. A 
blood sample will be obtained by venepuncture to be sent for sample storage locally or 
at a central laboratory, for potential HIV-1 RNA PCR and viral genotype resistance 
testing if the participant seroconverts (blood volume specified in Appendix C). Storage 
samples for participants who do not enrol will be destroyed according to local SOPs. 
 
If Test 1 is reactive, a highly specific HIV antibody Rapid Test (Test 2) will be performed. 
If Test 2 is reactive, the participant is considered to be HIV seropositive and not eligible 
for enrolment. Initial counselling services will be provided at the research centre and the 
woman will be referred for additional counselling, support services and treatment. 
 
If Test 1 is reactive and Test 2 is non-reactive (discordant rapid test results), collect 
samples for confirmatory testing by Bio-rad Geenius™, HIV-1 RNA PCR and other 
confirmatory tests as required. If the confirmatory test results are positive, the potential 
participant is considered to be HIV-seropositive and not eligible for enrolment. She will 
be counselled and referred to the local health facilities for appropriate follow-up. If the 
confirmatory test results are negative, the participant is considered to be HIV-
seronegative and the Enrolment Visit should be re-scheduled within the screening 
window period (split visit). Storage samples should be collected on the second day of the 
split visit. Refer to Appendix B: HIV Testing Algorithms. 
 
5.4.3. Trial Visits and LPUV 
The HIV rapid and confirmatory laboratory tests used in the HIV-testing algorithm will 
detect both subtypes, HIV-1 and HIV-2. The testing algorithm (refer to Appendix B) will 
be applied for all Trial Visits and LPUV. HIV testing while the participant is enrolled in the 
trial will be performed on blood samples obtained by venepuncture (blood volumes 
specified in Appendix C). 
 
If the highly sensitive HIV antibody rapid test (Test 1) is non-reactive, the participant will 
be considered HIV-seronegative and continue using the IP. If Test 1 is reactive, a highly 
specific HIV antibody Rapid Test (Test 2) will be performed on the same blood sample. If 
Test 2 is reactive, the participant will be considered to be HIV seropositive and IP will be 
discontinued. Trial procedures relevant to the LPUV will be performed and the participant 
will be counselled and referred for appropriate counselling and care. Additional 
confirmatory testing will be performed by Bio-rad Geenius™, HIV RNA PCR and other 
confirmatory tests, where appropriate, to confirm HIV-1 Seroconversion (refer to the 
Clinical Management Manual for more detail on this process). Samples for possible viral 
genotype resistance testing will be collected. IP may be re-introduced after consultation 
with IPM, if confirmatory test(s) indicate(s) that the participant is not HIV infected. In 
cases where anti-retroviral therapy has commenced, reintroduction of IP should be 
discussed with the IPM clinical physician before re-introducing IP. The participant must 
have a negative pregnancy test prior to re-introduction of IP. A pelvic examination should 
be performed according to the investigator’s discretion prior to re-introduction of IP, if 
clinically indicated. If confirmatory test(s) confirm HIV Seroconversion, the participant will 
be permanently discontinued from IP and the trial. Nucleic acid-amplification testing 
(NAAT) by a HIV-1 RNA PCR test will be performed on stored samples in reverse 
sequential order to estimate the time point of HIV infection. 
 
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Bio-rad Geenius™, HIV-1 RNA PCR and other confirmatory tests, where appropriate. 
Participants who have discordant HIV test results at Trial Visits will continue IP until HIV 
infection has been confirmed in consultation with the IPM Clinical Physician. If HIV 
infection is confirmed, trial procedures relevant to the LPUV will be performed. Samples 
for possible viral genotype resistance testing will be collected. If at any point IP was 
discontinued, IP may be re-introduced after consultation with IPM, if confirmatory test(s) 
indicate(s) that the participant is not HIV infected. The participant must have a negative 
pregnancy test result prior to re-introduction of IP. A pelvic examination should be 
performed according investigator’s discretion prior to re-introduction of IP, if clinical 
indicated.  If the confirmatory tests confirm HIV Seroconversion, Nucleic acid-
amplification testing (NAAT) by a HIV-1 RNA PCR test will be performed on stored 
samples in reverse sequential order to estimate the time point of HIV infection. The 
participant will be counselled and referred for appropriate counselling and care. 
All enrolled participants will in addition, have blood samples collected at each trial visit to 
be stored locally or at a central laboratory, for possible viral genotype resistance testing 
and HIV-1 RNA PCR testing. In the instance where additional HIV confirmatory testing 
needs to be performed at an unscheduled visit, blood samples for HIV RNA PCR and 
genotype testing will be collected. If a participant subsequently seroconverts (i.e. is 
confirmed HIV-positive) while participating in the trial, the stored samples will be tested 
in reverse sequential order until an undetectable PCR test result is obtained. This will be 
conducted to approximate the period of HIV infection. If the enrolment HIV-1 RNA PCR 
test result is positive, the participant is not considered to have been infected while using 
the IP. 
 
Blood (blood volume as specified in Appendix C) and vaginal fluid samples will also be 
obtained for dapivirine measurement at the point of HIV seroconversion according to the 
HIV testing algorithm described above. Stored samples (blood and vaginal fluids) will be 
analysed retrospectively as described in Section 5.17. 
 
Any participant who is confirmed HIV-infected while on the trial will be permanently 
discontinued from IP and the trial. An exit visit will be scheduled approximately 1-2 
months following IP discontinuation. Initial counselling services will be provided at the 
research centre and women will be referred for additional counselling, support services 
and treatment. In addition, these women will be offered the option of enrolling for IPM’s 
seroconverter protocol. 
 
In an instance where a participant is determined to be HIV-seropositive (as determined 
by HIV rapid tests, Bio-rad Geenius™, and any other confirmatory tests, if applicable), 
but cannot be confirmed as HIV-infected (HIV-1 RNA PCR) the participant will be 
discontinued from IP and the protocol-required procedures as per original trial visit 
schedule will be conducted at the investigator’s discretion. Samples for measurement of 
dapivirine levels will no longer be collected. Additional testing to demonstrate HIV 
infection may be performed. Participants will be followed up until the exit visit according 
to the original enrolment date. 
 
5.4.4. Exit Visit  
If the highly sensitive HIV antibody rapid tests (Test 1) is non-reactive, the participant will 
be considered HIV-seronegative. If Test 1 is reactive, a highly specific HIV antibody 
Rapid Test (Test 2) will be performed on the same blood sample. If Test 2 is reactive, 
the participant will be considered to be HIV seropositive. Initial counselling services will 


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be provided at the research centre and women will be referred for additional counselling, 
support services and treatment. 
 
Additional confirmatory testing will be performed by Bio-rad Geenius™, HIV-1 RNA PCR 
and other confirmatory tests, where appropriate (refer to the Clinical Management 
Manual for more detail on this process). Samples for possible viral genotype resistance 
testing will be collected. Once HIV infection has been confirmed, this will be considered 
an HIV seroconversion after product discontinuation and may be a combination of both 
women infected during IP use who seroconverted after IP discontinuation, as well as 
women infected after IP discontinuation. Nucleic acid-amplification testing (NAAT) by a 
HIV-1 RNA PCR test will be performed on stored samples in reverse sequential order to 
estimate the time point of HIV infection. 
 
If Test 1 is reactive and Test 2 is non-reactive (discordant results) samples will be 
collected for confirmatory testing by Bio-rad Geenius™, HIV-1 RNA PCR and other 
confirmatory tests, where appropriate (refer to the Clinical Management Manual for more 
detail on this process). Samples for possible viral genotype resistance testing will be 
collected. The participant will be counselled and referred to local health facilities for 
social support or other medical services as clinically indicated. Refer to Appendix B: HIV 
Testing Algorithms, and Appendix C: Visit Schedule and Blood Volumes. 
 
For participants confirmed as HIV-infected prior to the exit visit 
As stated in Section 5.4.3 above, an exit visit will be scheduled approximately 1-2 
months following confirmed HIV-seroconversion and IP discontinuation. Blood samples 
for viral genotype resistance testing and HIV-1 RNA PCR will be collected from these 
participants, but no further HIV counselling and testing will be done unless indicated for 
additional confirmatory testing. 
 
Participants who become infected with HIV during the course of an IPM trial will be 
referred for appropriate HIV-related care and ARV therapy as above. The threshold for 
initiation of ARV treatment will be determined with reference to the WHO treatment 
guidelines if no country specific guidelines are available. Women who become pregnant 
and HIV positive during the trial will be referred for appropriate Prevention of Mother-to-
Child Transmission (PMTCT) services. 
 
The research centres will inform IPM Medical Safety of any new HIV infections within 48 
hours of becoming aware of the HIV seroconversion. The applicable regulatory 
authorities and ethics committees who require expedited notification of HIV 
seroconversion will be notified by either IPM or the research centre in accordance with 
standard operating procedures and policies of the regulatory authorities or ethics 
committees. 
 
5.5. Contraceptive Counselling and Management of Contraception  
Contraceptive counselling will be provided at all research centre visits. Counselling will 
be tailored per research centre, depending on local community and regional guidelines 
and will be detailed in research centre procedures. Counselling will include information 
about medication side effects and interactions, the importance of contraceptive 
adherence for the duration of the trial; what to do in the event of accidental non-
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Participants will also be counselled that if they become pregnant during the trial, they will 
immediately discontinue the IP and be referred to the local prenatal services for support 
and further management of the pregnancy. Refer to Pregnancy Testing and 
Management below in Section 5.6. 
 
To meet eligibility criteria, unless postmenopausal with no history of menses for one year 
prior to screening, participants must be on an effective method of contraception prior to 
enrolment, have demonstrated adherence to her chosen method of contraception and 
have no significant resultant problems.  
 
In order to address challenges that participants may experience in consistently obtaining 
an effective method of contraception, research centres will provide participants with 
contraceptives from screening for the duration of the trial, if required. The contraceptives 
provided will be consistent with what is available locally. Alternatively, participants will be 
referred to the local family planning clinic or continue accessing contraception from local 
family planning clinics. Under supervision of the investigator or designated qualified 
personnel, enrolled participants may switch from one contraceptive method to another, if 
effective contraception is maintained. 
 
5.6. Pregnancy Testing and Management 
A urine pregnancy test will be performed at all scheduled trial visits, except for the Exit 
Visit, and can be performed additionally at unscheduled visits if any reason exists to 
suspect pregnancy or, in the event of a participant defaulting on her contraception, prior 
to recommencing contraception. 
 
If a potential participant tests positive for pregnancy during screening, she is not eligible 
to enrol in the trial, but will receive referrals to prenatal clinics or other appropriate 
facilities. 
 
A product hold will be implemented if a woman tests positive for pregnancy while on IP. 
Vaginal ring(s) will be retrieved from the participant, but the participant will not be 
withdrawn from the study. Protocol-specified visit schedule and procedures will continue 
except for IP-related procedures and other examinations if contra-indicated by 
pregnancy. The participant will be referred to a local prenatal clinic for medical services. 
The research centres will be asked to report all pregnancies to IPM within 48 hours of a 
positive pregnancy test or a confirmatory serum pregnancy test, if indicated. A 
confirmatory serum pregnancy test may be requested at the discretion of the investigator 
or a designated qualified member of the trial staff if reason exists to suspect a false 
positive urine pregnancy test. If the serum pregnancy test is negative, the investigator 
can consider recommencing use of the ring. If the participant indicates a change in 
pregnancy status or the participant’s clinical history indicates a change in her pregnancy 
status after the product hold (birth or termination), a urine pregnancy test may be 
performed. A confirmatory serum pregnancy test may be requested at the discretion of 
the investigator or a designated qualified member of the trial staff if reason exists to 
suspect a false positive urine pregnancy test. If the urine pregnancy test is negative, the 
investigator can consider recommencing IP. The participant must have a negative urine 
pregnancy test prior to re-introduction of IP, and should not be breast-feeding. A pelvic 
examination should be performed prior to re-introduction of IP. 


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Women who become pregnant and HIV-positive during the trial will be referred for 
appropriate PMTCT services. 
 
Should a participant have a positive pregnancy test in an instance where she was 
determined to be HIV-seropositive but could not be confirmed as HIV-infected, was 
discontinued from IP use and consented to continued participation in the trial without IP, 
she will be allowed to continue in the trial to allow for continued follow-up and evaluation 
of her HIV status until the Exit Visit according to the original enrolment date or until she 
is confirmed to be HIV-infected, whichever occurs earlier. 
 
The research centres will be required to provide quarterly updates on the progress and 
outcome of the pregnancy as well as the first year of life of the child for inclusion in the 
Sponsor maintained pregnancy registry. This requirement may vary, depending on 
country-specific regulations. 
 
5.7. Demographics and Medical History 
At the Screening Visit basic demographic information will be collected. A confidential 
master log of participants, with demographic and locator information will be maintained.  
 
At both the Screening and Enrolment Visits (pre-enrolment) relevant medical history will 
be obtained, including but not limited to history of STIs, gynaecological conditions, 
hospitalisations, surgery, allergies, any conditions requiring prescription or chronic 
medication, i.e. > 2 weeks in duration, and acute conditions occurring prior to enrolment. 
 
5.8. Physical Examination 
A general physical examination will be conducted at screening and the LPUV, and will 
include weight, vital signs (body temperature, pulse rate, respiration rate, blood 
pressure), and examination of skin, respiratory, cardiovascular, central nervous and 
abdominal systems, as well as an assessment of cervical and axillary lymph nodes. 
Height will be measured only at the Screening Visit. A symptom-directed physical 
examination will be conducted at any visit if clinically indicated. 
 
5.9. Pelvic Examination 
A pelvic examination will be performed at screening and LPUV, or at any visit if clinically 
indicated. On-trial examinations will be performed to assess safety, i.e., any local vaginal 
reactions. 
 
If the participant is menstruating on the day of a visit where pelvic examination is due, all 
procedures, including the pelvic examination can be conducted as per investigator and 
participant discretion. If this is not possible, the participant will be asked to return 2 days 
after completion of menstruation, within the window period of the visit. 
 
Any unexpected or abnormal vaginal bleeding should be investigated to identify the 
possible source. A follow-up pelvic examination should be performed to ensure 
resolution of the condition as indicated. 


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5.10. 
Laboratory testing for safety assessments and urine dipstick 
analysis 
Safety laboratory assessments and urine dipstick analysis (microscopy only if clinically 
indicated) will be conducted at the screening visit, or any other trial visit if clinically 
indicated.  Blood specimens for laboratory testing (haematology and chemistry testing) 
will be obtained by venepuncture. Haematology will include a full blood count, 
differential, and platelet count. Chemistry tests will include creatinine, AST and ALT. 
Details of blood volumes are specified in Appendix C. At the discretion of the investigator 
or designee, each potential participant may be retested once for safety laboratory tests 
during the screening period. 
 
Additional tests may be performed at the investigator’s discretion after discussion with 
the IPM Clinical Physician (or designee) based on symptomatology and clinical 
assessment of participants. Additional descriptive information regarding specimen 
collection and processing for all tests will be detailed in the SOM. 
 
All laboratory results will be reviewed by the investigator or appropriately qualified and 
trained trial staff as designated by the investigator, and documented on the original 
laboratory report itself. 
 
5.11. 
STI Testing and Management 
5.11.1. STI and Vaginal pH and Flora Testing 
Cervicovaginal samples will be collected for STI testing at screening and the LPUV, or 
any other trial visit if clinical indicated. All participants will be evaluated for Trichomonas 
vaginalis (TV), Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT). At 
screening, blood will be collected by venepuncture for Syphilis (RPR) testing (Blood 
volume specified in Appendix C). TPHA/TPPA testing will be performed if the RPR is 
reactive. Samples will be collected for assessment of vaginal flora and vaginal fluid pH at 
enrolment / screening and all subsequent visits except the exit visit.  
 
Additional descriptive information regarding specimen collection to test for STIs, vaginal 
flora and vaginal pH, and processing of all tests will be detailed in the Laboratory 
Manual, as part of the SOM. 
 
NOTE: Documentation will be made in applicable CRFs for all cervicovaginal samples 
obtained in the presence of cervicovaginal blood. 
 
The investigator or appropriately qualified and trained trial staff as designated by the 
investigator will review all results, including rapid and laboratory tests, and the review will 
be documented by the reviewer on the original laboratory report itself. 
 
5.11.2. STI Management 
All participants who present with STIs will be managed appropriately as clinically 
indicated at the research centre or referred to a local health facility, according to local 
STI Treatment Guidelines.  Cervicovaginal swabs may be collected from these 


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participants, at the investigator’s discretion or when required by local standard of care. 
Etiological management may be applicable following STI testing, according to the 
etiological diagnosis. 
 
The Clinical Management of Genital Diagnoses will be detailed in the SOM for guidelines 
to determine whether the vaginal ring requires temporary or permanent removal and to 
provide guidance regarding follow up recommendations.  
 
5.12. 
Cervical Cytology 
A cervical cytology sample will be collected at the Screening Visit if not done within the 
previous year, or if the result was abnormal at the last point of testing. Further details will 
be provided in the Laboratory Manual, as part of the SOM. 
 
Women with abnormal cytology findings will be referred for appropriate medical services 
based on local standard of care for management of abnormal cervical cytology. 
Research centres will implement these referral systems prior to trial start.  
 
5.13. 
Vaginal Ring Dispensing 
For the first 3 months of trial participation, all participants will be dispensed vaginal rings. 
At all follow-up visits following the first 3 months of trial participation, vaginal rings will be 
offered to all participants and dispensed to participants who opt to use the ring. In the 
event that a non-user decides to start using the ring again between scheduled trial visits, 
ring(s) may be dispensed at an unscheduled visit, following confirmation of negative 
pregnancy and HIV test results. 
 
In the event that a participant who opts to use the ring will be away and unable to attend 
one of the Trial Visits where new vaginal ring(s) would be dispensed, the investigator or 
designee could dispense additional ring(s) on a case-by-case basis. All such 
circumstances must be documented fully by the investigator as described in the IPM 032 
SOM. If a participant requires an additional ring at a time other than when they are 
scheduled to receive one, they will be required to attend the research centre for an 
interim visit.  During the monthly trial visit period, the participants will be instructed to 
self-insert the newly-dispensed vaginal ring at the research centre and to remove the 
ring at the next scheduled visit. After the first 3 months of trial participation, the 
participants who opt to use the ring should self-insert one ring during the trial visit and 
each of the two additional rings at monthly intervals until their next scheduled research 
centre visit. Vaginal ring bags will be provided to participants during the 3-monthly trial 
visit period for the storage of the used rings, together with instructions on the storage of 
the unused and used rings. 
 
During the 3-monthly trial visit period, optional vaginal ring dispensing and return 
arrangement will be made with participants who prefer not to have additional vaginal 
rings in their possession. These participants will be provided with the option to return 
used vaginal rings and to collect new rings at the research centres at time intervals 
suitable to them, provided that the intervals allow for new vaginal rings to be inserted 
monthly. Optional HIV rapid tests will be offered to participants during these interim visits 
and will be conducted according to the Trial Visits HIV algorithm (refer to Appendix B). 


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Participants’ preference regarding the intervals for product dispensing and return will be 
documented in the source document and applicable CRFs. 
 
5.14. 
Vaginal Ring Insertion and Ring Removal 
At the Enrolment and Trial Visits, participants will insert the vaginal rings under research 
centre supervision, as applicable. The participant will be instructed to thoroughly wash 
her hands, relax, and get into a comfortable position either standing with one foot on a 
chair, lying on her back with her knees up or squatting. After opening the folds of skin 
around the vagina, she will gently squeeze the ring into an oval shape and push it 
upwards and backwards towards the back as far as it will go, thereby depositing the ring 
in the vagina. She will then be instructed to thoroughly wash her hands again. At all 
research centre visits during which a pelvic examination is performed, the participants 
using the vaginal ring will remove the ring prior to the examination. 
 
If the participant requests help with either removal or insertion of the vaginal ring, or after 
she has made several attempts to remove/insert the ring without success, trained trial 
staff may give assistance. Re-education of the participant on ring removal/re-insertion 
will be given. This will be noted in the source documents and applicable CRFs. 
Additional instructions about ring use will be provided in the SOM. 
 
All rings that are removed will be inspected visually, and an assessment will be made by 
the principal investigator or designee as to whether the ring appears to have been used 
or not, together with a reason for the assessment. The rings should then be rinsed in 
running water, patted dry, placed in a ring return bag, and stored between 15°C and 
30°C until shipment to the analytical laboratory for testing of residual dapivirine amounts. 
 
5.15. 
Vaginal Ring Adherence Counselling 
At the Enrolment and Trial Visits, participants will receive vaginal ring adherence 
counselling, as applicable. All participants will receive counselling on compliance to trial 
visit schedule and requirements. IPM 032 participants will be provided with feedback on 
the IPM 027 and MTN-020 trials, which will include information on trial adherence trends, 
as part of the vaginal ring adherence counselling. Research centre staff will counsel 
participants to refrain from removing the ring (except as directed during research centre 
visits) and will provide instructions to all participants in case of accidental ring expulsion 
(e.g., during sex or exercise), or removal, and guidance will be provided on how the ring 
should be handled when it is out of the vagina. Research centre staff will also provide 
instructions to the participants during the 3-monthly trial visit period for insertion of a new 
ring after a month and the participants will be counselled on how to store the used and 
unused rings at home, if applicable.  
 
If, for any reason, the participant is non-adherent to the use of the vaginal ring (i.e. she 
removes the ring for any purpose other than as instructed at a trial visit), this should be 
documented according to the guidelines specified in the SOM.  
 


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5.16. 
Qualitative Behavioural Assessments 
Each research centre will conduct two to three in-depth individual interviews (IDIs) with 
approximately six participants in each of the following categories:  
 
Decliner Population  
 
Ring Users 
 
Ring Non-users 
 
In cases of interest IDIs will be conducted; approximately three participants will be 
interviewed per site. These cases of interest may include, but will not be limited to 
participants who may have experienced social harms, may have had problems using the 
ring, or who HIV seroconverted 
 
Focus group discussions may also be conducted with the above mentioned groups. 
Efforts will be made to ensure the sample size is representative of both previous IPM 
027 participants as well as the two ring-naïve cohorts of women. Additionally, IDIs and/or 
FGDs with approximately six males from the community and/or male partners will be 
conducted at each research centre.  
 
DVR-naïve participants will complete a behavioural questionnaire at enrolment, in 
addition to the participant questionnaire collected at other trial visits. 
 
These assessments will provide data on acceptability and influencers of ring use. The 
recruitment and sampling strategy will be specified in the study operations manual. 
 
 
5.17. 
Quantitative Behavioural Assessments 
5.17.1. Participant Questionnaire 
The Participant Questionnaire will be administered at every trial visit and the LPUV 
for all enrolled participants. This questionnaire includes acceptability questions about 
the monthly and 3-monthly research centre follow-up during the trial. Ring use 
related questions will not be collected from Ring Non-users. 
 
5.17.2. Baseline Behavioural Questionnaire for DVR-naïve Cohorts   
A baseline behavioural questionnaire will be completed for all DVR-naïve Cohort 
participants at the enrollment visit. 
 
5.17.3. Decliner Population Participant Questionnaire 
Participants who decline participation in IPM 032 will be asked to provide written 
informed consent to collect information on their reasons for declining participation. If 
they are willing to participate in the questionnaire interview, participants will be given 
the choice of meeting the interviewers at a convenient location in the field or at the 
research centre. Questionnaires may be completed telephonically after written 
informed consent has been obtained from the participant.   
 
This information will be captured in a decliner population questionnaire, and may be 
collected retrospectively. A decliner population ID (DP-ID) will be assigned to each 


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participant. Written informed consent will be obtained from all participants in the 
decliner population to be contacted for participation in further behavioural 
assessments (e.g. qualitative in-depth interviews (IDIs) and / or focus group 
discussion (FGD)), either on-site or at an off-site location. Written informed consent 
will be obtained prior to IDIs and FGDs.  
 
5.18. 
Sample Storage and Analysis 
Blood (blood volume as specified in Appendix C) and vaginal fluid samples will be 
collected for storage locally or at a central laboratory at all research centre visits. Blood 
samples for HIV viral genotype resistance testing and HIV-1 RNA PCR will be stored at 
the Screening Visit, the Enrolment Visit, every Trial Visit, LPUV and Exit Visit and will be 
tested subsequent to confirmed HIV-1 seroconversion, according to the HIV testing 
algorithm described in Section 5.4. Testing will also be conducted on a random sample 
of HIV-negative participants. For possible dapivirine concentration measurements, 
plasma and vaginal fluid samples should preferably be collected prior to removal of the 
vaginal ring, for the Ring User population. Further details regarding these procedures will 
be provided in the Laboratory Manual, as part of the SOM. 
 
All specimens will be collected and analysed according to methods described in the 
Laboratory Manual and research centre SOPs for proper collection, processing, 
labelling, and transport of specimens to the laboratories conducting the analysis. Where 
possible and appropriate, stored specimens will be re-tested to assess validity of 
unusual or unexpected assay results. 
 
Any residual specimens will be destroyed at the end of the trial after all protocol-required 
and quality control testing has been completed. 
5.19. 
Screening Identification (SCR-ID) and Participant Identification (PID) 
Numbers 
After informed consent is obtained, a SCR-ID number will be assigned to each 
participant for identification purposes and the participant will be screened to assess 
eligibility for the trial. As each new participant enters the trial, a unique PID number will 
be assigned in consecutive order, starting with the lowest number available at the 
research centre at the time. 
 
After informed consent is obtained, previous IPM 027 participants who decline 
participation in IPM 032 will be assigned a DP-ID number. Numbers will be assigned 
in consecutive order, starting with the lowest number available at the research centre at 
the time. 
 
5.20. 
Diary cards 
Participants will be provided with diary cards at enrolment and at trial visits, as 
applicable, except the LPUVs and Exit Visits. The diary cards are meant to be completed 
by the participants, and returned to the research centre at each Trial Visit and the LPUV 
to serve as a memory aid for participants to review during their scheduled visits and 
adherence counselling. The diary card will be used to document the removal and 


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insertion date of the additional rings and for documenting AEs experienced and 
concomitant medications taken between trial visits. Participants will be requested to 
document the details of all cases of accidental ring expulsion or removal. Additional 
instructions on diary cards will be provided in the SOM. 
 
5.21. 
Reimbursement 
Participants will be reimbursed for any travel costs incurred in compliance with local 
regulations. Reimbursements will be made after the completion of each trial visit. 
Research centre specific reimbursement amounts will be documented in the trial ICF 
approved by the applicable IRB/IEC. Upfront reimbursement for travel expenses may be 
made if this has been approved by the relevant ethics committee. 
Note: During the 3-monthly trial visit period, participants who choose to not receive the 
two additional vaginal rings during trial visits, will be responsible for the travel costs 
incurred during the optional vaginal ring collection/return visits to the research centre. 
 
5.22. 
Participant Compensation 
If a participant in an IPM clinical trial becomes ill or injured as a result of participation in 
the trial, medical treatment for the adverse reaction or injury will be provided 
appropriately. The research centre staff will refer the participant for ongoing treatment for 
the injury, if needed. The Sponsor will be responsible for compensation for appropriate 
medical expenses for treatment of any such illness or injury. An HIV infection that occurs 
during the course of the trial will not be considered an injury or illness caused by trial 
participation. 
 
5.23. 
Participant Responsibility 
Referral systems to local medical services will be implemented by research centres prior 
to trial start. It remains the participant’s responsibility to follow up with relevant medical 
services once referral has been initiated by the research centre. 
 
5.24. 
Study Operations Manual (SOM) 
A SOM will be supplied to all research centres to provide general guidance on the 
conduct of trial procedures. The Laboratory Manual is contained within the SOM. 
6. Investigational Product  
6.1. Investigational Product Composition 
The dapivirine silicone elastomer vaginal matrix ring is an off-white flexible ring 
containing 25 mg of dapivirine dispersed in a platinum-catalysed silicone matrix. The 
dimensions of the ring are 56 mm (outer diameter) and 7.7 mm (cross sectional 
diameter). The dapivirine silicone elastomer vaginal matrix ring is designed to provide 
sustained release of dapivirine over a minimum of one month. 
 


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The Dapivirine Vaginal Ring-004 is comprised of dapivirine, the polydimethylsiloxane 
liquid MED-360 and the silicone MED-4870. The safety of dapivirine has been 
established in a comprehensive nonclinical and clinical development programme 
described in the IB14. Both the silicone elastomers and the liquid silicone dispersant have 
been evaluated in in vitro cytotoxicity, haemolysis tests, cytogenic damage and 
genotoxicity assays, and in in vivo systemic toxicity studies, intracutaneous toxicity 
studies, pyrogen studies and delayed contact sensitisation studies. The silicone 
elastomer was also evaluated in muscle implantation studies of up to 12 weeks duration. 
In addition, a number of preclinical tests were performed on the finished Dapivirine 
Vaginal Ring-004, including a panel of biocompatibility tests (in vitro cytotoxicity and 
genotoxicity assays, and in vivo vaginal irritation and sensitisation studies) using extracts 
of the ring, and a study in sheep, in which Dapivirine Vaginal Ring-004 containing 25 mg 
dapivirine was inserted into the vagina (up to 3 consecutive rings; each ring for a period 
of 30 days). None of these tests identified any significant safety concerns. 
 
6.2. Packaging and Labelling 
IPM will bear the responsibility for primary and secondary packaging and labelling. The 
packaged rings will be labelled according to local regulatory requirements. 
 
6.3. Investigational Product Storage 
The recommended storage condition for the dapivirine ring is 15°C to 30°C, excursions 
permitted. The proposed shelf life is 48 months when stored in the original packaging 
under the recommended storage conditions. In the event that the IP has been subjected 
to different storage conditions than specified above, the affected IP will not be used 
(unless IPM or its designee provides written authorisation for use). IPM should be 
notified immediately in the event that IP storage conditions have been breached. 
 
The investigator (or pharmacist) will maintain an inventory and acknowledge receipt of all 
shipments of IP. More information on IP storage will be provided in the SOM. 
 
Participants will be provided with instructions on storage of used and unused rings 
during the 3-monthly trial visit schedule, as applicable. 
 
6.4. Investigational Product Administration  
The participants will be instructed to self-insert the Dapivirine Vaginal Ring-004 at the 
Enrolment Visit, and monthly thereafter. The participants will be reminded of proper 
vaginal ring insertion and removal procedures.  
 
During the 3-monthly trial visit schedule, participants who opt to use the Dapivirine 
Vaginal Ring-004 will be instructed to remove the vaginal ring and self-insert each of the 
two additional rings at monthly intervals until their next scheduled research centre visit. 
The self-insertion and removal of the rings should take place at the research centres 
during the months that the participants attend their scheduled trial visits.  Participants 
should be advised to continue ring use through menses. 
 


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6.5. Investigational Product Expulsion or Loss 
If a participant accidentally expels the ring, e.g., during sex or exercise, she will be 
instructed to rinse the vaginal ring thoroughly in clean water and re-insert the ring as 
soon as possible. If the vaginal ring is expelled and cannot be successfully reinserted, 
the ring should be appropriately rinsed, patted dry and stored in the bag provided for this 
purpose, until the earliest possible opportunity the participant can return for help with the 
reinsertion of a ring at the research centre.  
 
During monthly visits, if the ring is expelled in such a manner that the participant is 
unwilling to re-insert it, e.g., during urination or a bowel movement, or if the ring is lost, 
the participant should return to the research centre at the earliest possible opportunity to 
receive a replacement ring.  
 
During the 3-monthly trial visit schedule, participants will be instructed that if the ring is 
expelled in such a manner that the participant is unwilling to re-insert it, e.g., during 
urination or a bowel movement, or if the ring is lost, the participant should use one of the 
unused, additional rings dispensed. If the expelled ring was the last of the additional 
vaginal rings dispensed, the participant should return to the research centre at the 
earliest possible opportunity to receive a replacement ring.  
 
Also, in cases where a ring is removed due to a genital infection, a new ring will be 
inserted or dispensed. Visits associated with expulsion or loss of rings will be regarded 
as unscheduled visits unless the visit is within the 7-day window period of the next 
scheduled visit. 
 
6.6. Retrieval of Investigational Product 
All participants who are prematurely discontinued from the trial will be encouraged to 
return to the research centre for a final evaluation, at which time all vaginal rings in the 
participant’s possession should be retrieved. If the participant does not return her used 
or unused vaginal ring at this visit, it should be retrieved as soon as possible after this 
visit, either by the participant returning it to the trial staff, or by trial staff conducting a 
home visit. 
 
For participants who are considered lost to follow-up and permanently discontinued from 
the trial, reasonable contact attempts will be made according to the locator information 
provided by the participant and local SOPs. Any used or unused vaginal rings that could 
not be retrieved will be documented in the source documents and applicable CRFs. 
6.7. Investigational Product (IP) Accountability 
The principal investigator or designee will be responsible for adequate and accurate 
accounting, handling, storage and dispensing of the IP. The IP will be stored safely and 
properly in a secure location with access available only to the principal investigator and 
designated trial personnel. IP and clinical supplies are to be dispensed only in 
accordance with the protocol. Accurate records of IP received from IPM, the amount 
dispensed to the participants, the amount returned by the participants, the quantity 
remaining at the conclusion of the trial and any wasted or expired IP will be maintained. 
 


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Unused and used rings not analysed for residual amounts of dapivirine will be destroyed 
according to IPM instruction and local regulatory requirements. 
 
6.8. Concomitant Medications and Products 
Prescription and non-prescription medications will be recorded on the source documents 
and applicable CRFs. Vaginal products and practices including the use of spermicides, 
intravaginal medication, douches, lubricants, tampons and female condoms may be 
used during the trial and will be captured. Further details will be provided in the SOM. 
7. Adverse Events 
7.1. Definition 
An AE is any untoward medical occurrence during the course of a trial in a participant 
who received an IP at any dose, which does not necessarily have a causal relationship 
with the IP. An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom or disease temporally associated with the use of 
an IP, whether or not considered related to the IP. This definition includes inter-current 
illnesses or injuries and exacerbation of pre-existing conditions. 
 
An unexpected adverse event is an adverse event, the nature or severity (intensity) of 
which is not consistent with the applicable product information (i.e. IB, package insert, or 
summary of product characteristics). Final determination of whether an event is 
considered unexpected will be made by the Sponsor, however, the investigator should 
be knowledgeable of the contents of the IB. 
 
Whenever possible, the laboratory abnormalities should be considered in the context of 
the primary clinical diagnosis and should be reported as such (e.g. acute hepatitis with 
increased bilirubin). Clinically significant laboratory abnormalities will be considered AEs 
and graded for severity based on the Division of AIDS (DAIDS Table for Grading 
Severity of Adult and Pediatric Adverse Events) as appropriate. 
 
Any condition occurring prior to enrolment will be reported as a pre-existing condition 
under Medical or Gynaecological History. All AEs occurring during the trial will be 
recorded in the source documents and applicable CRFs.  All AEs will be reported and 
graded according to the latest version of the DAIDS Table for Grading Severity of Adult 
and Pediatric Adverse Events and Female Genital Grading Table for Use in Microbicide 
Studies (which will be provided to research centres in the SOM). A vaginal bleeding 
abnormality thought to be due to contraception, asymptomatic BV and asymptomatic 
candidiasis will not be reported as an AE for this trial. 
 
If a unifying diagnosis is possible, the investigator should record a specific disease or 
syndrome rather than individual associated signs and symptoms. However, if an 
observed or reported sign, symptom, or clinically significant laboratory abnormality is not 
considered a component of a specific disease or syndrome by the investigator, it should 
be recorded as a separate AE. 
 
All AEs will be monitored until resolution and/or the cause are identified, or until the 


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investigator does not expect any improvement or worsening of condition/symptoms. If a 
SAE, urogenital AE or related AE remains unresolved at the participant’s Exit Visit, the 
research centre investigator will make a clinical assessment with the IPM Clinical 
Physician to determine whether continued follow-up of the AE is warranted. All other AEs 
that are not serious, not urogenital and assessed to be unrelated to IP will be noted as 
ongoing at trial end if the outcome is not yet determined at the time of the exit visit. 
 
7.2. Assessment of Adverse Event Severity 
The investigator is responsible for assessing the severity of AEs occurring on trial. All 
AEs except genital complaints will be graded according to the latest version of the 
DAIDS Table for Grading Severity of Adult and Pediatric Adverse Events. All genital 
complaints will be graded according to the latest version of the Female Genital Grading 
Table for Use in Microbicide Studies, which will be provided to research centres in the 
SOM. 
 
For AEs not listed on either of these tables, the following criteria will be used to estimate 
the grade of severity: 
 
Mild 
Symptoms causing no or minimal interference with usual social and functional 
activities 
 
Moderate 
Symptoms causing greater than minimal interference with usual social and 
functional activities 
 
Severe 
Symptoms causing inability to perform usual social and functional activities 
 
Potentially Life-threatening 
Symptoms causing inability to perform basic self-care functions OR medical 
or operative intervention indicated to prevent permanent impairment, 
persistent inability, or death 
 
7.3. Relationship to Investigational Product 
The investigator is responsible for determining the relationship of all AEs occurring 
during the trial and will assess AEs based on the following criteria: 
 
Not Related 
There is not a temporal relationship or a reasonable possibility of a causal 
relationship (i.e. some level of evidence is lacking) to administration of the 
investigational product. The AE is clearly explained by another cause 
(concurrent disease, concomitant medication, environmental or toxic factors, 
etc.). 
 
Related 
There is a reasonable possibility of a causal relationship between the 
investigational product and the AE, (i.e. there is some level of evidence as to 
the causal association). The event may respond to withdrawal of the 


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investigational product (dechallenge), and recurs with rechallenge by 
administration of the investigational product. In other cases the AE is clearly 
related and most likely explained by the administration of the investigational 
product. 
 
7.4. Serious Adverse Event 
7.4.1. Serious Adverse Event Definition 
A serious adverse event (SAE) or reaction is any untoward medical occurrence that at 
any dose: 
 
Results in death. 
 
Is life-threatening. 
This criterion applies if the participant is at immediate risk of death from the 
event as it occurred, in the opinion of the investigator; it does not refer to an 
event which hypothetically might have caused death if it were more severe. 
 
Requires in patient hospitalisation or prolongation of existing 
hospitalisation. 
This criterion applies if the event requires inpatient hospitalisation and results 
in an overnight stay in hospital or, if in the opinion of the investigator, 
prolongs 
an 
existing 
hospitalisation. 
A 
hospitalisation 
(including 
hospitalisation for an elective procedure or routinely scheduled treatment not 
associated with an adverse event) for a pre-existing condition which has not 
worsened does not constitute an SAE. 
 
Results in persistent or significant disability/incapacity. 
This criterion applies if the event causes a substantial disruption of a person’s 
ability to conduct normal life functions. 
 
Is a congenital anomaly/birth defect. 
This criterion applies if a participant gives birth to a child with a congenital 
anomaly or birth defect or if the anomaly/birth defect is diagnosed by any 
prenatal tests. 
 
Important medical events (medically significant) that may not be 
immediately life-threatening or result in death or hospitalisation but may 
jeopardize the participant or may require intervention in order to prevent one 
of the outcomes listed above should also be considered serious; e.g., 
bronchospasm requiring intensive treatment in an emergency room or at 
home. 
NOTE: A SAE does not have to be severe in nature to meet any of the above criteria. 
 
All SAEs that occur from the time the participant is enrolled through the duration of the 
trial, whether considered associated with the IP or not, must be reported to the IPM 
Medical Safety Physician and/or designee within 24 hours of the centre becoming aware 
of the event. All SAEs should be recorded in the source documents and the relevant 
CRFs and reported using the Immediately Reportable Events (IRE) Form provided. 
 
The IRE Report Form should be completed with all the available information at the time 
of reporting. The investigator is required to write a detailed report and complete SAE 


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follow up in a timely manner until the SAE has resolved, the participant returns to normal 
health, or until the investigator does not expect any further improvement or worsening of 
the condition. Medical Records may be requested by IPM to assist in assessing 
relatedness and severity of the SAE, and for possible submission to the Regulatory or 
Health Authorities as appropriate. To maintain confidentiality, the participant’s name 
must be blacked out on any medical records submitted and replaced with the PID 
number and the initials. 
 
More details on SAE reporting requirements and processes are described in the Safety 
Reporting Plan (provided in the SOM) provided to the research centres. 
 
7.4.2. Serious Adverse Event Contact Information 
 
SAEs will be reported to IPM or designee within 24 hours of any research centre staff 
member becoming aware of the event. If the SAE is related, and life-threatening or fatal, 
IPM Medical Safety should additionally be notified immediately by email or telephone. 
 
The following email will be used for communication with the IPM Medical Safety team 
regarding any IREs: safetyreports@ipmglobal.org. Contact details of relevant safety 
personnel will be provided in the Safety Reporting Plan. 
 
IPM or designee will process all safety events. The IPM Medical Safety Physician or 
designee will review all SAEs and generate the necessary queries. Further SAE 
reporting guidelines will be specified in the Safety Reporting Plan. 
 
7.4.3. Sponsor Notification of SAEs to the Regulatory Authorities 
Any unexpected serious adverse events which are deemed related to investigational 
product, will be considered “associated with the use of investigational product” and, as 
such, IPM will notify the appropriate regulatory authorities of the event in an expedited 
manner unless policies of the local regulatory authorities mandate such reporting by the 
research centre.  
 
Any unexpected SAE deemed to be unrelated to the IP will not be reported to the 
regulatory authorities in an expedited manner, unless policies of the local regulatory 
authorities mandate such reporting. 
 
7.4.4. Research Centre Notification of SAEs to Local Independent Ethics 
 Committee or Local Health and Regulatory Authorities 
The investigator will report all SAEs to the local IEC and/or regulatory or health 
authorities in accordance with standard operating procedures and policies of the IEC 
and/or regulatory or health authorities. 
 
7.5. Immediately Reportable Events 
These are events which, while not necessarily meeting criteria for seriousness, are 
considered important by IPM and as such warrant immediate reporting to IPM. The 
following events should be reported to the Sponsor within 48 hours of any research 
centre staff member becoming aware of the event: 


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 
Pregnancy: Although not considered an AE, pregnancy must be reported if it 
occurs at any time while on IP during the trial;  
 
HIV infection any time during the trial;  
 
Any non-serious AE (including laboratory abnormalities) leading to permanent 
discontinuation of the investigational product.  
 
All IREs that occur from the time the participant is enrolled should be reported to IPM 
within the time periods specified above. All IREs should be recorded in the source 
documents and the relevant CRFs and should be reported to the IPM Medical Safety 
Physician using the IRE Form provided. 
 
As with SAEs, the IRE form should be completed with all available information at the 
time of reporting. The investigator is required to follow up the IRE in a timely manner 
until such time as it is deemed appropriate by IPM that all relevant information has been 
collected, or until such time as the participant is lost to follow up. 
 
7.6. Safety Monitoring 
The IPM 032 trial team will monitor safety and participant recruitment throughout the trial 
for all participants. Safety data from the trial will be evaluated by an independent Data 
and Safety Monitoring Board (DSMB). The first scheduled meeting will take place 
approximately six months after all research centres have been activated and thereafter 
at approximately annual intervals for the duration of IPM 032. Based on the review of the 
data, the DSMB is required to provide recommendations about continuation, pausing, 
termination or other modifications to the trial, including changes to the information 
provided to participants for obtaining their informed consent. An IPM 032 DSMB charter 
will describe the roles and responsibilities of the DSMB, its composition, data to be 
provided to the DSMB, the process for disseminating trial data to the DSMB, and the 
communication plan between the DSMB and IPM. 
 
7.7. Data Handling at Research Centres 
All trial data will first be collected on designated source documents and then recorded on 
CRFs with the exception of the Participant Questionnaires, for which the CRFs will serve 
as the source document, unless otherwise specified by IPM. Research centre staff 
responsible for completing the CRFs will receive appropriate training prior to the start of 
the trial, and will follow standardised procedures. Data must be legibly entered onto the 
CRFs. Data corrections will be made in accordance with standard procedures provided 
by IPM or its designee. Instructions for CRF completion will be provided on the back of 
the CRF pages, as well as in the SOM.  
 
The investigator will maintain, and store in a secure manner, complete, accurate and 
current trial records throughout the trial. Standard GCP practices will be followed to 
ensure accurate, reliable and consistent data collection. 
 


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7.8. Source Data Verification 
All trial data must be verifiable to the source documentation (which includes original 
recordings, laboratory requisitions and reports, medical records, etc.). Source 
documentation will be made available to the IPM or representative(s) for review to 
ensure that the collected data is consistent with CRFs and has been completely and 
accurately reported as required by the trial protocol. 
8. Statistical Methods  
IPM 032 is a Phase IIIb, multi-centre, open-label follow-on trial to IPM 027 to evaluate 
and compare the safety of and adherence to Dapivirine Vaginal Ring-004, inserted at 
monthly intervals between healthy, HIV-negative women who have participated in the 
IPM 027 trial and the DVR-naïve women.  
 
All women who have participated in IPM 027 and are HIV-negative at screening for IPM 
032 will be eligible. Two additional cohorts of women aged ≥18 to ≤21 years and >21 to 
<25 years, who have not previously used the Dapivirine Vaginal Ring-004 (DVR-naïve 
women), will be enrolled. Individuals meeting all inclusion criteria and no exclusion 
criteria will be eligible to receive the Dapivirine Vaginal Ring-004 with monthly research 
centre follow-up for one month (which may be extended to three months at the 
investigator’s discretion) followed by 3-monthly research centre follow-up visits.  
 
Up to 1400 participants from the IPM 027 trial and approximately 300 participants for 
each of the two additional cohorts are expected to be enrolled in the trial. Total 
estimated enrollment in the trial will be approximately 2000 participants. 
 
Participants will self-insert the vaginal rings. Once participants commence the period of 
3-monthly follow up visits, two additional rings will be dispensed at each trial visit, the 
first of which the participants should self-insert one month later, and the second ring one 
month after that, before returning to the research centre for their next scheduled visit.  
 
An exit visit will be conducted approximately 1-2 months after removal of the last ring 
(last product use visit). Exit visits will be optional for participants who are Ring Non-users 
at the point of trial termination. 
  
8.1. Trial Endpoints  
The primary, secondary and exploratory trial endpoints are described in detail in Section 
2.2 of the protocol. 
 
8.2. Primary Trial Hypotheses 
From previous clinical and safety trials of dapivirine, it is now known that the Dapivirine 
Vaginal Ring-004 is safe, well tolerated and reduces the risk of acquiring HIV-1 infection. 
These results also showed little to no protection against HIV-1 infection in younger 
women (aged 18-21 years). Further research is needed to understand younger women’s 
unique challenges in using HIV prevention methods, therefore, the primary hypotheses 
for this trial will be to compare safety and adherence data between the former IPM 027 


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participants and the DVR-naïve women.  
 
8.3. Sample Size and Power Calculations 
This trial will be conducted in approximately 2000 healthy, HIV-negative women. This 
includes up to 1400 women who have participated in the IPM 027 trial and two additional 
cohorts of approximately 300 women each, ≥18 to ≤21 years and >21 to <25 years 
respectively, who have not used the Dapivirine Vaginal Ring-004 previously (DVR-naïve 
Cohorts). No formal sample size or power calculations have been performed. It is 
expected that up to 70% of the participants enrolled in IPM 027 will participate in this 
trial. Therefore, a total sample size of up to 1400 former IPM 027 participants is 
anticipated. In a trial with this number of participants assigned to the IP, there is a 95% 
probability of detecting an AE occurring at a rate of 0.3% or higher. 
 
8.4. Statistical Analyses 
The primary analysis will focus on safety as well as adherence assessments.  
 
The primary analysis will be performed under the intent-to-treat (ITT) principle, which will 
include all participants enrolled in the trial.  As it is possible that the inclusion of non-
adherent participants or participants who discontinued from the IP may artificially lower 
the rates of safety outcomes, additional analyses will be conducted on the per-protocol 
population, which will include only participants who were adherent to the protocol. 
Details on the definition of the per-protocol population, in addition to models that will be 
used to examine the exploratory objectives and other technical aspects of these 
analyses will be provided in a SAP, which will be finalised prior to final database lock. 
 
The analysis of the secondary safety assessments will be mainly descriptive in nature. 
The incidence density rate of HIV-1 seroconversion and the frequency of HIV-1 drug 
resistance in women who seroconvert will be summarised descriptively.   
 
Other objectives will also be explored: 
1. The feasibility of 3-monthly follow-up visits, as a possible schedule for post-
licensure vaginal ring clinical follow-up 
2. The correlation between drug concentrations and results from the visual 
inspection of the returned vaginal rings by research staff between the monthly 
and 3-monthly research centre follow-up schedules 
3. The proportion of participants electing to undergo HIV rapid tests at the research 
centres between scheduled 3-monthly visits 
4. The characteristics of the IPM 027 participants who decline enrollment into IPM 
032 (Decliner Population) 
5. Self-reported acceptability of and adherence to the 25 mg Dapivirine Vaginal 
Ring-004. 
 
Primary, secondary and exploratory analyses will be conducted comparing the following 
groups of participants: 
 
Former IPM 027 participant Ring Users; Ring Non-users will be included in 


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safety comparison 
 
The total of the DVR-naïve women (All) 
 
The two cohorts of DVR-naïve women  
 
The data will be presented using appropriate statistical measures including, but not 
limited to: mean, standard deviation, median, and interquartile range for continuous data; 
frequency and relative frequency for categorical data. When appropriate, 95% 
confidence intervals and p-values will be presented.       
 
8.4.1. Primary Safety Analysis 
A descriptive analysis of all AEs will be presented in tables and listings. AEs will be 
summarised by MedDRA System Organ Class (SOC) and Preferred term (PT). The 
proportion of participants experiencing adverse events, including the proportion of 
participants experiencing product-related adverse events, Grade 3 or 4 AEs, or SAEs, 
will be determined The difference in incidence between the relevant groups of 
participants and the corresponding 95% confidence intervals will be presented. The 
confidence intervals will be determined based on linear regression with robust standard 
errors, with research centre as covariate. In addition, AE dot plots will be prepared to 
graphically display the difference in incidence rates.  
All data will be presented per cohort within research centre, and per cohort overall 
across research centres.  
 
8.4.2. Primary Adherence Analysis 
Residual levels of dapivirine in returned rings and/or plasma and/or vaginal fluid 
concentrations of dapivirine will be used as measures of adherence to ring use. The data 
will be listed, summarised and presented graphically for the two cohorts. The ring 
residual levels and/or plasma and/or vaginal fluid concentrations of dapivirine associated 
with non-adherence will be informed by the results from IPM 027, and will be described 
in detail in the SAP, which will be finalised prior to final database lock. The correlation 
between the amount of residual dapivirine in the used rings and the corresponding 
plasma and/or vaginal fluid levels of dapivirine will be explored graphically and 
summarised descriptively.  
 
8.4.3. Secondary Analyses 
 
Incidence of HIV-1 seroconversion 
The number of HIV-1 seroconversions, the incidence density rate of HIV-1 
seroconversion, i.e. HIV-1 seroconversion rate per 100 woman-years of product use at 
the end of the ring use period, as well as a 95% CI for the HIV-1 seroconversion rate per 
100 woman-years based on the normal approximation of the Poisson distribution will be 
presented for each cohort within research centre, and per cohort overall across research 
centres. Kaplan-Meier curves will be presented similarly.  
 
 
HIV-1 drug resistance 
The analysis of HIV-1 drug resistance will be primarily descriptive in nature, and will 
depend on the pattern of resistance mutations observed in the HIV-1 seroconverters.  
The resistance associated mutations observed will be listed by participant, and a 


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frequency tabulation of individual resistance mutations associated with the various 
classes of antiretrovirals, e.g. Protease Inhibitors, Nucleoside Reverse Transcriptase 
Inhibitors and Non-nucleoside Reverse Transcriptase Inhibitors, will be produced. The 
proportion of HIV-1 seroconverters with at least one HIV-1 drug resistant mutation will be 
presented per cohort within research centre, and per cohort overall across research 
centres, with the corresponding 95% CI. 
 
8.4.4. Exploratory analyses 
 
The feasibility of 3-monthly follow-up visits, as a possible 
schedule for post-licensure vaginal ring clinical follow-up 
Results of the Participant Questionnaires will be summarized per cohort within research 
centre and per cohort overall across research centres. Ring use related questions will 
not be collected from Ring Non-users. 
 
 
The correlation between drug concentrations and results 
from the visual inspection of the returned vaginal rings by research 
staff between the monthly and 3-monthly research centre follow-up 
schedules 
The proportion of returned rings (used and unused) during the 3-monthly clinical follow-
up schedule, the visual inspection of, as well as the actual drug concentration levels, in 
the returned rings will be summarised per cohort within research centre and per cohort 
overall across research centres. Any correlation between the visual inspection of the 
returned rings and the actual drug concentration levels will be descriptive in nature, and 
will be summarised based on data available at the time of analyses. 
 
 
The proportion of participants electing to undergo HIV rapid 
tests at the research centres between scheduled 3-monthly visits 
Frequencies and percentages of the number of participants who undergo HIV rapid tests 
at the different research centres, will be summarised per cohort within research centre 
and per cohort overall across research centres. 
 
 
Characterization of IPM 027 participants who declined 
enrollment into IPM 032 (Decliner Population) 
Participants from the IPM 027 trial, who decline participation in IPM 032 and who meet 
all the other inclusion criteria and none of the exclusion criteria for the Decliner 
Population, will be included in the Decliner Population. Participant Questionnaires will be 
completed by either meeting with the participants, or by telephonic interview. Reasons 
for declining participation, will be summarised per research centre and overall across 
research centres. 
 
 
Self-reported acceptability of and adherence to the 25 mg 
Dapivirine Vaginal Ring-004 
Frequencies and percentages of the following will be summarised per cohort within 
research centre and per cohort overall across research centres: 
 
women who report the use of the vaginal ring as acceptable,  
 
women who opt not to receive two additional rings at the 3-monthly visits, 


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 
self-reported patterns of ring use. 
 
8.4.5. Other results from Qualitative/Quantitative Behavioural assessments 
Each research centre will conduct two to three in-depth individual interviews (IDIs) with 
approximately six participants in each of the following categories:  
 
Decliner Population  
 
Ring Users 
 
Ring Non-users 
 
In cases of interest IDIs will be conducted; approximately three participants will be 
interviewed per site. These cases of interest may include, but will not be limited to 
participants who may have experienced social harms, may have had problems using the 
ring, or who HIV seroconverted. Focus group discussions may be conducted with the 
above mentioned groups. Efforts will be made to ensure the sample size is 
representative of both previous IPM 027 participants as well as the two ring-naïve 
cohorts of women. Additionally, IDIs and/or FGDs with approximately six males from the 
community and / or male partners will be conducted at each research centre.  
 
DVR-naïve participants will complete a behavioural questionnaire at enrolment, in 
addition to the participant questionnaire collected at other trial visits.  
 
These assessments will provide data on acceptability and influencers of ring use and will 
be summarised. 
 
8.4.6. Other data collected 
Statistical analyses of other data collected during the trial, which are not mentioned in 
section 8, will be detailed in the SAP. 
 
8.4.7. Interim Analysis 
No interim analysis is planned for this trial. However, the Sponsor will review the 
treatment emergent safety data at regular intervals during the conduct of the trial.  
8.5. Data and Safety Monitoring Board 
Safety data from the trial will be evaluated by an independent Data and Safety 
Monitoring Board (DSMB). The first scheduled meeting will take place approximately six 
months after all research centres have been activated and thereafter at approximately 
annual intervals for the duration of IPM 032. Based on the review of the data, the DSMB 
is required to provide recommendations about continuation, pausing, termination or 
other modifications to the trial, including changes to the information provided to 
participants for obtaining their informed consent. An IPM 032 DSMB charter will describe 
the roles and responsibilities of the DSMB, its composition, data to be provided to the 
DSMB, the process for disseminating trial data to the DSMB, and the communication 
plan between the DSMB and IPM. 
8.6. Handling of Missing Data and Dropouts 
Some degree of missing data, primarily associated with missed visits, is expected. The 


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amount of missing data will be explored and incorporated into the analyses, where 
appropriate. For the analysis of adherence to monthly ring use, patterns of missing data 
may be informative. Depending on the proportion of participants who discontinue early, 
an analysis of time to discontinuation may be conducted. Such an analysis would allow 
investigation of the covariates associated with early discontinuation and could provide 
information that would be useful in designing future trials of other microbicide rings. 
Patterns of missing data may also provide further insight into participants’ preference for 
monthly or 3-monthly follow-up visits to research centres. 
9.  Investigator Requirements 
9.1. Trial Initiation 
The trial can be initiated at the research centre once all relevant IRB/IEC and regulatory 
approvals have been obtained in compliance with country specific requirements, and the 
relevant essential documents are available on file. Following IPM approval, IPM will 
notify the research centre in writing via letter correspondence to begin trial operations 
according to the protocol. 
 
9.2. Institutional Review Boards or Independent Ethics Committee Approval 
This protocol, the informed consent document, and relevant supporting information will 
be submitted to the IRBs/IECs for review and must be approved before the trial is 
initiated. 
 
The principal investigator is responsible for communicating with IRBs/IECs regarding the 
progress of the trial and changes made to the protocol as deemed appropriate, at least 
once a year. The principal investigator will also keep the IRBs/IECs informed of any 
significant AEs and SAEs, in accordance with standard operating procedures and 
policies of the IRB/IEC. 
 
9.3. Trial Monitoring and Audits 
Trial monitors will regularly visit participating research centres to review trial documents 
including, but not limited to individual participant records, consent forms, source 
documents, CRFs, supporting data, laboratory specimen records and medical records 
(physicians’ progress notes, nurses’ notes, individuals’ hospital charts) to ensure 
protection of trial participants, compliance with the protocol, and accuracy and 
completeness of records. The trial monitors will also inspect the research centre’s 
regulatory files to ensure that regulatory requirements are being followed; the research 
centre’s pharmacies to review product storage, management, and drug accountability; 
and the research centre’s laboratory and other clinical supplies to ensure proper storage 
and continued viability of supplies. All applicable trial documents should be readily 
available for review during the visits. The trial monitors will also check that clinical trial 
procedures are observed and will discuss any problems with investigator or designee as 
applicable. 
 
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and/or representatives of the IPM may request access to all trial documents for on-site 
research centre audit or inspection. 
 
9.4. Case Report Forms (CRFs) 
CRFs will be supplied by IPM or its designee and will be handled in accordance with 
instructions from IPM. 
 
All CRFs will be completed by the designated trial staff in accordance with the 
instructions provided by IPM. Upon trial completion, the CRF is reviewed, signed, and 
dated by an investigator listed on the Statement of Investigator, Form FDA 1572. 
 
All CRFs will be completed in a neat, legible manner to ensure accurate interpretation of 
data. Black ink is required to ensure clarity. When making changes or corrections, the 
original entry will be crossed out with a single line, and the change initialed and dated. 
Erasures, overwriting, and correction fluid are NOT allowed on the CRFs. 
 
9.5. Disclosure of Data 
Participant medical information is confidential and disclosure to third parties other than 
those described in Section 9.3 is strictly prohibited. All trial data will be stored securely at 
the research centre. All participant information including laboratory reports, forms, lists, 
logbooks, appointment books and administrative forms will be stored in locked file 
cabinets or rooms in areas with access limited to trial staff. 
 
Participants’ trial information will not be released without written permission of the 
participant, except as necessary for monitoring by the Sponsor, Sponsor’s designated 
monitors, regulatory authorities, or local IRBs/IECs. 
 
9.6. Record Retention 
The principal investigator will retain in a secure manner, complete, accurate and current 
trial records for a minimum of two years after marketing approval or termination of 
product development. Trial records include administrative documentation, including 
research centre registration documents and all reports and correspondence relating to 
the trial, as well as documentation related to each participant screened and/or enrolled in 
the trial, including ICFs, CRFs, notations of all contacts with the participant, and all other 
source documents. All records must be retained on-site throughout the trial’s period of 
performance. IPM will provide the research centre with written instructions for long-term 
record storage at the completion of the trial. 
 
No records should be destroyed without prior written permission from IPM. 
10. Ethical Considerations 
10.1. 
Ethical Review 
This protocol, research centre-specific informed consent documents, participant 


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education, outreach, recruitment materials and any other requested documents or 
subsequent modifications will be reviewed and approved by the ethical review bodies 
responsible for oversight of research conducted at the research centre. 
 
Subsequent to initial review and approval, the local IRB and/or IEC will be notified about 
trial completion within three months following trial termination or completion. This trial will 
be conducted in accordance with: 
 
World Medical Association Declaration of Helsinki17 
 
ICH GCP guidelines18  
 
Applicable national ethics and regulatory requirements in countries where the 
trial is being conducted, e.g. Guidelines for Good Practice in the Conduct of 
Clinical Trials in Human Participants in South Africa19.  
 
10.2. 
Reporting and Management of Social Harms related to trial 
participation 
Social harms, e.g., disruption of family or personal relationships may result due to 
participation in this trial becoming known to others. In addition, IP use could potentially 
be unacceptable to the participant’s sex partner and result in difficulties with her sex 
partner. If a participant is or becomes HIV-infected, she may also experience social 
harms. 
 
During each HIV counselling session, enrolled participants will be asked questions to 
assess the occurrence of social harms related to trial participation. Participants who 
experience social harms considered to be related to trial participation will be counselled 
accordingly and provided with assistance to mitigate the circumstances if possible. This 
will be recorded in the source documents and applicable CRFs. 
 
10.3. 
Community Engagement 
Community Liaison Officers have been appointed at each research centre to oversee the 
information provided to local stakeholders, target population and general community. 
They have been tasked with capturing, monitoring and evaluating feedback from the 
community. Comments will be captured in various ways at each research centre using 
methods such as suggestion boxes, door-to-door campaigns, large and small community 
dialogue sessions, pre/post-tests, distributed feedback forms, etc. Each research centre 
has a process for consulting with its community. The primary vehicle for this consultation 
is 
through 
formal 
structures 
such 
as 
the 
Community 
Advisory 
Boards/Groups/Committees. These systems allow investigators and communities to 
identify and respond rapidly to concerns raised. 
11.  Publications 
Any presentation, abstract, or manuscript shall be reviewed and approved by the 
Sponsor prior to submission. Publication of the results of this trial will be governed by the 
IPM’s clinical trial agreement with the investigator.  Authorship criteria will be based on 
contributions to the design, work, and analysis of the trial. 


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12. References 
1. Nel A, Van Niekerk N, Kapiga S, et al.  Safety and Efficacy of a Dapivirine 
Vaginal Ring for HIV Prevention in Women. N Engl J Med, 2016 Dec 1; 375: 
2133-2143. 
 
2. Baeten JM, Palanee-Phillips T, Brown ER, et al. Use of a Vaginal Ring 
Containing Dapivirine for HIV-1 Prevention in Women. N Engl J Med, 2016 Dec 7 
2016; 375: 2121-2132. 
 
3. Regional Fact Sheet 2012. Sub-Saharan Africa. 
http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2
012/gr2012/2012_FS_regional_ssa_en.pdf 
4. AIDS by the numbers; UNAIDS 2013. 
http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspublicati
on/2013/20131120_AIDSbynumbers_A5brochure_en.pdf 
5. Ombati, The Feminization of HIV in Sub-Saharan Africa. Africa Policy Journal, 
2012. 
 
6. UNAIDS, HIV Prevention among adolescent girls and young women, 2016, 
UNAIDS: Geneva, Switzerland. 
 
7. UNAIDS, AIDS By the Numbers- 2016, 2016, UNAIDS: Geneva, Switzerland. 
 
8. UNAIDS, 2016 UNITED NATIONS POLITICAL DECLARATION ON ENDING 
AIDS SETS WORLD ON THE FAST-TRACK TO END THE EPIDEMIC BY 2030, 
2016, UNAIDS: New York, NY/ Geneva, Switzerland. 
 
9. Elias CJ, Coggins C. Female-controlled methods to prevent sexual transmission 
of HIV. AIDS 1996;10:S43-S51 
 
10. Karim SSA, Richardson BA, et al. Safety and effectiveness of BufferGel and 
0.5% PRO2000 gel for the prevention of HIV infection in women. AIDS 2011; 
25(7):957. 
 
11. Nel A, Kapiga S, Bekker LG, et al. Safety and Efficacy of Dapivirine Vaginal Ring 
for HIV-1Prevention in African Women. Abstract number 110LB at Conference on 
Retroviruses and Opportunistic Infections2016: Boston, MA.  
 
12. Baeten JM, Palanee-Phillips T, Brown ER, et al. A Phase III Trial of the 
Dapivirine Vaginal Ring for HIV-1 Prevention in Women. Abstract number 109LB 
at Conference on Retroviruses and Opportunistic Infections (CROI) 2016, CROI: 
Boston, MA. 
 
13. Brown E, Palanee-Philips T, Marzinke M. et al. Residual dapivirine ring levels 
indicate higher adherence to vaginal ring is associated with HIV-1 protection. 
AIDS Conference 2016, Durban, South Africa. 
 
14. Dapivirine Vaginal Ring Investigator’s Brochure, Version 10.0, 09 March 2016.  


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15. IPM 011; Clinical Study Report; Version 1.0, 15 March 2011. 
 
16. IPM 015; Clinical Study Report; Version 1.0, 06 July 2012. 
 
17. World Medical Association Declaration of Helsinki. Ethical Principles for Medical 
Research Involving Human Subjects; WMA General Assembly, Fortaleza, Brazil, 
October 2013. http://www.wma.net/en/30publications/10policies/b3/index.html 
 
18. Guidance for Industry: E6 Good Clinical Practice: Consolidated Guidance. 
http://www.fda.gov/downloads/Drugs/Guidances/ucm073122.pdf 
 
19. 21 Guidelines for Good Practice in the Conduct of Clinical Trials in Human 
Participants in South Africa. http://www.kznhealth.gov.za/research/guideline2.pdf


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APPENDIX A: SCHEDULE OF PROCEDURES 
Visits 
Pre‐
screening 
Screening 
Enrolment 
Trial Visits 
LPUV 
Exit Visit 
As needed 
Trial Months 
Screening 
must occur 
within 45 
days of 
enrolmentk 
0 
 Months 1‐11h,i 
Month 12i 
Months 13‐
14i 
Contact potentially eligible participants 
X 
 
 
 
 
 
 
Informed Consent  
 
X 
 
 
 
 
 
Comprehension Assessment 
 
X 
 
 
 
 
 
Assign Screening Identification Number 
 
X 
 
 
 
 
 
Assign Participant Identification Number  
 
 
X 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
Medical History 
 
X 
X 
 
 
 
 
Concomitant Medication Evaluation 
 
X 
X 
X 
X 
X 
X 
Inclusion/Exclusion Criteria  
 
X 
X 
 
 
 
 
Locator Information 
 
X 
X 
X 
X 
 
 
Basic Menses Information 
 
X 
X 
X 
X 
 
 
Physical Examination 
 
X 
 
 
X 
 
X 
Adverse Event Evaluation 
X 
X
X
X
X
Social Harms Assessment 
 
 
X 
X 
X 
X 
X 
Pelvic Exam 
 
X 
 
 
X 
 
X 
Vaginal Ring Dispensing and Insertionm 
 
 
X 
X 
 
 
 
Vaginal Ring Return/Collection m 
 
 
 
X 
X 
 
 
Visual  Inspection of Returned Ring(s) m 
 
 
 
X 
X 
 
 
Provision of Vaginal Ring Use and Storage Instructions m 
 
 
X 
X 
 
 
 
Vaginal Ring Adherence Counselling m 
 
 
X 
X 
 
 
 
Collect  information  for  stopping  and/or  re‐initiating  ring 
use  
 
 
 
 
 
 
X 
Provision of Diary Card(s) 
 
 
X 
Xj 
 
 
 
Collection of Diary Card(s) 
 
 
 
X 
X 
 
 
Participant Questionnaire 
 
 
 
Xa 
X 
 
 
Baseline Behavioural Questionnaire – DVR‐Naïve Cohorts 
 
 
X 
 
 
 
 
In‐depth  individual  interviews  and/or  focus  group 
discussions 
 
 
 
 
 
 
Xn 


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Visits 
Pre‐
screening 
Screening 
Enrolment 
Trial Visits 
LPUV 
Exit Visit 
As needed 
Trial Months 
Screening 
must occur 
within 45 
days of 
enrolmentk 
0 
 Months 1‐11h,i 
Month 12i 
Months 13‐
14i 
HIV/STI Risk Reduction Counselling 
 
X 
X 
X 
X 
X 
 
Contraceptive Counselling 
 
X 
X 
X 
X 
X 
X 
Provision of and/or referral for Contraceptives 
 
X 
X 
X 
X 
X 
X 
Provision of Male and/or Female Condoms (if participant 
wishes to receive them) 
 
X 
X 
X 
X 
X 
 
Urine Pregnancy Test (hCG)  
 
X 
X 
X 
X 
 
X 
Cervicovaginal 
Sample 
Collection 
for 
STI 
Tests
Trichomonas  vaginalis  (TV),  Neisseria  gonorrhoeae  (NG) 
and Chlamydia trachomatis (CT) 
 
X 
 
 
 
X 
 
X 
Provision of treatment and/or referral for STIs and Other 
Findings 
 
 
 
 
 
 
X 
HIV Pre‐ & Post‐Test Counselling 
 
X 
X 
X 
X 
X 
 
HIV Rapid Tests b 
 
X 
X 
X 
X 
X 
X 
HIV‐1 RNA PCR Test c, d 
 
X 
X 
X 
X 
X 
 
Plasma Viral Genotype Sample c, d 
 
X 
X 
X 
X 
X 
 
Plasma Dapivirine Concentrations m 
 
 
 
X 
X 
 
 
Vaginal Fluid Dapivirine Concentrations m 
 
 
 
X 
X 
 
 
Laboratory Testing for Safety Assessments e 
 
X 
 
 
 
 
X 
Urine  Dipstick  Analysis  (Urine  Microscopy  if  Clinically 
Indicated Only) 
 
X 
 
 
 
 
X 
Vaginal Fluid pH and Vaginal Flora Sample 
 
 
X 
X 
X 
 
 
RPR f 
 
X 
 
 
 
 
 
Cervical Sample Collection for Cytology g 
 
X 
 
 
 
 
X 
Final Laboratory results provided 
 
 
 
 
 
X 
 
DECLINER POPULATION 
Informed Consent 
X 
 
 
 
 
 
 
Assign Decliner Population ID (DP‐ID) 
X 
 
 
 
 
 
 
Decliner Population Questionnaire l 
X 
 
 
 
 
 
 
In‐depth  individual  interviews  and/or  focus  group 
discussions 
X n 
 
 
 
 
 
 


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16 January 2017 
Version 2.0 Amendment 2.0 
 
 
 
 
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a) 
Participant Questionnaire will be administered at all Trial Visits. 
b) 
Performed in accordance with HIV testing algorithm 
c) 
Sample will be stored and will only undergo testing subsequently or after confirmation of seroconversion and at every visit for seroconverters, or if required by HIV testing 
algorithm. 
d) 
Sample will be obtained at the point of two reactive HIV rapid tests and analysed subsequently or after confirmation of seroconversion. 
e) 
Blood draw by venepuncture for laboratory testing (haematology and chemistry). Haematology will include full blood counts, differential, and platelet count. Chemistry tests 
will include creatinine, AST and ALT. 
f) 
TPHA/TPPA should be performed if RPR positive. 
g) 
Cervical sample collection for cytology may be conducted at any study visit if no result is evident within the previous year, or abnormal at last cervical cytology. 
h) 
All women will attend a research centre follow-up visit one month after enrolment.  Following this visit, at investigator’s discretion, a participant can continue on a 3-monthly 
visit schedule. Monthly visits may however be extended up to the first three months of participation. 
i) 
IPM will have the option to extend the trial period. 
j) 
Participants will receive a diary card at enrolment and at trial visits, as applicable.  Returned diary cards will be reviewed at all scheduled trial visits.  
k) 
Only procedures in bold italics required for participants rolling over directly from LPUV at IPM 027 to IPM 032. 
l) 
Previous IPM 027 participants who decline enrollment in IPM 032 will be asked to provide written informed consent to complete a decliner population questionnaire either 
telephonically or in person, and to ascertain their willingness to be selected to participate in IDI and/or FGDs 
m) 
Not applicable to participants who opt to not use the ring (non-users) at any point following the first 3 months of trial participation. 
n) 
IDIs and/or FGDs will be conducted amongst selected participants at appropriate time points for individual participants  
 
 
 


IPM 032 
 
    
 
 
16 January 2017 
Version 2.0 Amendment 2.0 
 
 
 
 
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APPENDIX B: HIV TESTING ALGORITHM 
 
Figure 1: Screening Algorithm 
 
 
 
TEST 1 
Non-reactive 
▼ 
HIV-seronegative 
TEST 2 
Reactive 
Potentially HIV-seronegative 
▼ 
Potentially eligible for enrolment 
Reactive 
▼ 
HIV-seropositive 
Non-reactive 
▼ 
Discordant 
Not eligible for enrolment 
▼ 
Refer for appropriate 
counselling and care 
Potentially eligible for enrolment 


IPM 032 
 
    
 
 
16 January 2017 
Version 2.0 Amendment 2.0 
 
 
 
 
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Figure 2: Pre-Enrolment Algorithm 
 
 
 
TEST 1 
Non-reactive 
▼ 
HIV-seronegative 
TEST 2 
Reactive 
Collect samples for confirmatory 
testing 
Reactive 
▼ 
HIV-seropositive 
Non-reactive 
▼ 
Discordant 
Not eligible for enrolment 
▼ 
Refer for appropriate counselling and 
care 
Enrol 
▼ 
Collect samples for 
storage 
If detectable: 
Not eligible for enrolment 
▼ 
Refer for appropriate 
counselling and care 
If Undetected: 
Enrol 
▼ 
Collect samples for 
storage 
If confirmatory tests are 
Inconclusive  
▼ 
Additional confirmatory testing will 
be done to determine if the 
participant is HIV infected or not 


IPM 032 
 
    
 
 
16 January 2017 
Version 2.0 Amendment 2.0 
 
 
 
 
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Figure 3: Trial Visits Algorithm 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
Refer for appropriate 
counselling and care 
TEST 1 
Non-reactive 
▼ 
HIV-seronegative 
TEST 2 
Reactive 
Collect samples for 
storage 
▼ 
Continue IP use 
Reactive 
▼ 
HIV-seropositive 
Non-reactive 
▼ 
Discordant
Draw samples for HIV 
seroconversion 
If confirmed as HIV 
Negative 
▼ 
Recommence  
(* or continue) IP use 
If confirmed as HIV-1 
Seroconversion 
 
Discontinue IP use (if 
applicable) 
▼
Refer for appropriate 
counselling and care 
If confirmatory tests are 
Inconclusive  
▼ 
* Discuss IP use 
 
Additional confirmatory testing 
will be done to determine if the 
participant is HIV infected or not
Discontinue IP 
Continue IP*  


IPM 032 
 
    
 
 
16 January 2017 
Version 2.0 Amendment 2.0 
 
 
 
 
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Figure 4: LPUV Algorithm 
 
 
 
TEST 1 
Non-reactive 
▼ 
HIV-seronegative 
TEST 2 
Reactive 
Collect samples for 
storage 
Non-reactive 
▼ 
Discordant 
Draw samples for HIV 
seroconversion 
confirmation  
If confirmed as HIV 
Negative 
▼ 
Schedule Exit Visit 
If confirmed as HIV-1 
Seroconversion 
▼ 
Ship stored samples for 
analysis 
Refer for appropriate 
counselling and care 
If confirmatory tests are 
Inconclusive  
▼ 
Additional confirmatory testing 
will be done to determine if the 
participant is HIV infected or not
Refer for appropriate 
counselling and care 
Reactive 
▼ 
HIV-seropositive


IPM 032 
 
    
 
 
16 January 2017 
Version 2.0 Amendment 2.0 
 
 
 
 
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Figure 5: Exit Visit Algorithm 
Non-reactive 
▼ 
HIV-seronegative 
TEST 2 
TEST 1 
Reactive 
Reactive 
▼ 
HIV-seropositive
Non-reactive 
▼ 
Discordant
Draw samples for HIV 
seroconversion 
confirmation  
If confirmed as HIV 
Negative 
▼ 
Complete Exit visit 
If confirmed as HIV-1 
Seroconversion 
▼ 
Ship stored samples for 
analysis 
Refer for 
appropriate 
counselling and 
care 
If confirmatory tests are 
Inconclusive  
▼ 
Additional confirmatory testing will 
be done to determine if the 
participant is HIV infected or not 
Refer for appropriate 
counselling and care 


IPM 032 
 
16 January 2017 
Version 2.0 Amendment 2.0 
 
Page 82 of 83 
 
 
 
 
 
 
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APPENDIX C: VISIT SCHEDULE AND APPROXIMATE BLOOD VOLUMES 
 
Visit 
Test and 
volume 
(mL) 
Test and 
volume 
(mL) 
Test and 
volume 
(mL) 
Test and 
volume 
(mL) 
Test and 
volume 
(mL) 
Total 
Blood 
Volume 
Screening 
HIV rapid* 
5 mL 
 
Chemistry 
5 mL 
Haematology 
5 mL 
RPR 
5 mL 
HIV viral 
genotype 
resistance#  
10 mL 
HIV PCR# 
5 mL 
35mL 
 
 
 
 
 
 
 
Enrolment 
HIV rapid 
5 mL 
 
 
HIV viral 
genotype 
resistance#  
10 mL 
HIV PCR# 
5 mL 
20 mL 
 
 
 
 
 
 
 
Trial Visits 
HIV rapid 
5 mL 
Dapivirine 
levels#∞ 
6 mL 
 
HIV viral 
genotype 
resistance#  
10 mL 
HIV PCR# 
5 mL 
26 mL 
 
 
 
 
 
 
LPUV 
HIV rapid 
5 mL 
Dapivirine 
levels# ∞ 
6 mL 
 
HIV viral 
genotype 
resistance#  
10 mL 
HIV PCR# 
5 mL 
26 mL 
 
 
 
 
 
 
 
Exit Visit 
HIV rapid^ 
5 mL 
 
 
HIV viral 
genotype 
resistance## 
10 mL 
HIV PCR# / 
## 
5 mL 
5 mL or 
15 mL## 
 
 
 
 
 
 
 
Seroconverter 
tests+ 
Bio-Rad 
Geenius 
2mL 
Dapivirine 
levels++ ∞ 
6 mL 
 
HIV viral 
genotype 
resistance#  
10 mL 
HIV PCR# 
5 mL 
17 mL++ or 
23 mL 
 
 * Depending on the research centre SOP on HIV testing, sampling may be performed 
by finger prick or venepuncture.  
 # Stored plasma samples; tested retrospectively to evaluate different parameters at 
the time of seroconversion.  
 ## Blood samples for viral genotype resistance and HIV-1 RNA PCR testing will be 
collected at the scheduled exit visit following seroconversion.  
 ^ HIV rapid testing will not be conducted at the scheduled exit visit following 
seroconversion.  
 
+ At the point of seroconversion, these samples will be collected and tested in addition 
to relevant visit-specific tests, but no samples should be duplicated during the same 
visit. No additional storage samples will be collected.  
NOTE: Additional tests may be also performed, as required.  
 
++ Test sample for possible dapivirine measurements will not be required if the 
seroconversion occurs at the Exit Visit. 
 ∞ Not applicable to Ring Non-users.


IPM 032 
 
    
 
 
16 January 2017 
Version 2.0 Amendment 2.0 
 
 
 
 
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APPENDIX D: TRIAL DESIGN 
 
 
 
 
 
 
 
   
 
 
 
 
 
MONTH 12
RING USE DISCONTINUED 
 
DAY 0 
RING INSERTION 
LPUV 
EXIT VISIT 
1-2 months 
≤ 45 days 
Monthly trial visit schedule 
 
First month after enrolment  
(or up to 3 months after enrolment at 
investigator’s discretion) 
3-monthly trial visit schedule 
2 additional rings dispensed at each trial visit, or 
dispensed as arranged 
ENROLMENT 
Approximately 
2000 women 
SCREENING 
MONTH 3 
After 3 months:  
Option to stop and re-initiate ring use 

Prot_000.pdf: 
 
IPM 032 
Protocol 
 
CONFIDENTIAL 
CLIN-TEM-GEN-0001.00, 13Jan2016 
 
Page 1 of 1 
 
NCT02862171 
 
IPM 032 
 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF AND 
ADHERENCE TO THE DAPIVIRINE (25 mg) VAGINAL RING-004 IN HEALTHY, HIV-NEGATIVE 
WOMEN  
 
• 
Protocol Version 2.0 Amendment 4.0 dated 17 October 2019 
 


IPM 032 
Version 2.0 Amendment 4.0 
17 October 2019 
Page 1 of 75
Restricted * Confidential – Limited Access* 
IPM 032 
Version 2.0 Amendment 4.0 
17 October 2019 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF AND 
ADHERENCE TO THE DAPIVIRINE (25 mg) VAGINAL RING-004 IN HEALTHY, 
HIV-NEGATIVE WOMEN  
Phase IIIb 
SPONSOR: 
International Partnership for Microbicides 
8401 Colesville Road, Suite 200 
Silver Spring, MD 20910 USA 
Phone: 1-301-608-2221 
Fax: 1-301-608-2241 
After 01 June 2017:  
International Partnership for Microbicides  
8405 Colesville Road, Suite 600 
Silver Spring, MD 20910 USA 
Phone: 1-301-608-2221 
Fax: 1-301-608-2241 


17-Oct-2019 | 09:30:47 EDT
1PM 032 
Version 2.0 Amendment 4.0 
SIGNATURE PAGE 
1PM 032 
17 October 2019 
Page 2 of 3 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF 
AND ADHERENCE TO THE DAPNIRINE (25 mg) VAGINAL RING-004 IN 
HEAL THY, HIV-NEGATIVE WOMEN 
I have read this protocol and appendices and agree to conduct the trial as stipulated and 
in compliance with the principles of the World fv1edical Association Declaration of Helsinki, 
the 
International 
Council 
for 
Harmonisation 
of 
Technical 
Requirements 
for 
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines, and all 
applicable regulations and guidelines. 
Investigator Signature 
Date 
Investigator Name 
Research Centre Name 
On behalf of the International Partnership for Mcrobicides, I confirm that the sponsor will 
com ply with all obligations as detailed in all applicable regulations and guidelines. I will 
ensure that the investigator is informed of all relevant information that becomes available 
during the conduct of this trial. 
Chief fv1edical Officer Signature 
Annalene Nel, MBChB, PhD 
Chief fv1edical Officer Name (Printed) 
Date 
( 
DocuSigned by: 
I Annalene Nel 
IJ 
Signer Name: Annalene Nel 
L
Signing Reason: I approve this document 
Signing Time: 17-0ct-2019 I 09:30:42 EDT 
37B32E6FC3224758B4A116172FB6AC09 
Restricted* Confidential - Limited Access* 


17-Oct-2019 | 09:30:47 EDT
Dr. C Louw
30-Oct-2019 | 07:01:56 EDT
Madibeng 
Centre for 
Research
1PM 032 
Version 2.0 Amendment 4.0 
SIGNATURE PAGE 
1PM 032 
17 October 2019 
Page 2 of 3 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF 
AND ADHERENCE TO THE DAPNIRINE (25 mg) VAGINAL RING-004 IN 
HEAL THY, HIV-NEGATIVE WOMEN 
I have read this protocol and appendices and agree to conduct the trial as stipulated and 
in compliance with the principles of the World fv1edical Association Declaration of Helsinki, 
the 
International 
Council 
for 
Harmonisation 
of 
Technical 
Requirements 
for 
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines, and all 
apPH~abiei9f'egtltations and guidelines. 
I Dr. C Louw 
V 
Signer Name: Dr. C Louw 
L
Signing Reason: I approve this document 
Signing Time: 30-0ct-2019 I 07:01 :28 EDT 
B25CED25D1AB47B289F32334647B15C0 
Investigator Signature 
Investigator Name 
Date 
Research Centre Name 
On behalf of the International Partnership for Mcrobicides, I confirm that the sponsor will 
com ply with all obligations as detailed in all applicable regulations and guidelines. I will 
ensure that the investigator is informed of all relevant information that becomes available 
during the conduct of this trial. 
Chief fv1edical Officer Signature 
Annalene Nel, MBChB, PhD 
Chief fv1edical Officer Name (Printed) 
Date 
( 
DocuSigned by: 
I Annalene Nel 
V 
Signer Name: Annalene Nel 
L
Signing Reason: I approve this document 
Signing Time: 17-0ct-2019 I 09:30:42 EDT 
37B32E6FC322475BB4A116172FB6AC09 
Restricted* Confidential - Limited Access* 


17-Oct-2019 | 09:30:47 EDT
MatCH Research Unit
Prof J Smit
04-Feb-2020 | 22:55:21 PST
1PM 032 
Version 2.0 Amendment 4.0 
SIGNATURE PAGE 
1PM 032 
17 October 2019 
Page 2 of 3 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF 
AND ADHERENCE TO THE DAPNIRINE (25 mg) VAGINAL RING-004 IN 
HEAL THY, HIV-NEGATIVE WOMEN 
I have read this protocol and appendices and agree to conduct the trial as stipulated and 
in compliance with the principles of the World fv1edical Association Declaration of Helsinki, 
the 
International 
Council 
for 
Harmonisation 
of 
Technical 
Requirements 
for 
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines, and all 
applicable regulations and guidelines. 
( 
DocuSigned by: 
I 
Prof J Smit 
IJ 
Signer Name: Prof J Smit 
l 
Signing Reason: I approve this document 
_ 
Signing Time: 04-Feb-2020 I 22:54:50 PST 
<--- BA4 I f!;A;!je9~M4M I BEeBeeeDD046BiB<0G 
Investigator Signature 
Date 
Investigator Name 
Research Centre Name 
On behalf of the International Partnership for Mcrobicides, I confirm that the sponsor will 
com ply with all obligations as detailed in all applicable regulations and guidelines. I will 
ensure that the investigator is informed of all relevant information that becomes available 
during the conduct of this trial. 
Chief fv1edical Officer Signature 
Annalene Nel, MBChB, PhD 
Chief fv1edical Officer Name (Printed) 
Date 
( 
DocuSigned by: 
I 
Annalene Nel 
IJ 
Signer Name: Annalene Nel 
L
Signing Reason: I approve this document 
Signing Time: 17-0ct-2019 I 09:30:42 EDT 
37B32E6FC3224758B4A116172FB6AC09 
Restricted* Confidential - Limited Access* 


17-Oct-2019 | 09:30:47 EDT
Dr. PL Kotze
Qhakaza 
Mbokodo 
Research 
Clinic
01-Nov-2019 | 00:21:55 PDT
1PM 032 
Version 2.0 Amendment 4.0 
SIGNATURE PAGE 
1PM 032 
17 October 2019 
Page 2 of 3 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF 
AND ADHERENCE TO THE DAPNIRINE (25 mg) VAGINAL RING-004 IN 
HEAL THY, HIV-NEGATIVE WOMEN 
I have read this protocol and appendices and agree to conduct the trial as stipulated and 
in compliance with the principles of the World fv1edical Association Declaration of Helsinki, 
the 
International 
Council 
for 
Harmonisation 
of 
Technical 
Requirements 
for 
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines, and all 
a~bleig-regU;tlations and guidelines. 
I Dr. PL Kotze 
{J 
Signer Name: Dr. PL Kotze 
L
Signing Reason: I approve this document 
Signing Time: 01-Nov-2019 I 00:21 :39 PDT 
84B97DBB4BAF434CB2C6DBA2DD5255D8 
Investigator Signature 
Investigator Name 
Date 
Research Centre Name 
On behalf of the International Partnership for Mcrobicides, I confirm that the sponsor will 
com ply with all obligations as detailed in all applicable regulations and guidelines. I will 
ensure that the investigator is informed of all relevant information that becomes available 
during the conduct of this trial. 
Chief fv1edical Officer Signature 
Annalene Nel, MBChB, PhD 
Chief fv1edical Officer Name (Printed) 
Date 
( 
DocuSigned by: 
I Annalene Nel 
{J 
Signer Name: Annalene Nel 
L
Signing Reason: I approve this document 
Signing Time: 17-0ct-2019 I 09:30:42 EDT 
37B32E6FC322475BB4A116172FB6AC09 
Restricted* Confidential - Limited Access* 


17-Oct-2019 | 09:30:47 EDT
Dr. S Kusemererwa
MRC/UVRI and 
LSHTM Uganda 
Research Unit
30-Oct-2019 | 09:14:38 PDT
1PM 032 
Version 2.0 Amendment 4.0 
SIGNATURE PAGE 
1PM 032 
17 October 2019 
Page 2 of 3 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF 
AND ADHERENCE TO THE DAPNIRINE (25 mg) VAGINAL RING-004 IN 
HEAL THY, HIV-NEGATIVE WOMEN 
I have read this protocol and appendices and agree to conduct the trial as stipulated and 
in compliance with the principles of the World fv1edical Association Declaration of Helsinki, 
the 
International 
Council 
for 
Harmonisation 
of 
Technical 
Requirements 
for 
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines, and all 
a~E>Jei~l!J~tions and guidelines. 
I Dr. S Kusemererwa 
V 
Signer Name: Dr. S Kusemererwa 
L
Signing Reason: I approve this document 
Signing Time: 30-Oct-2019I09:14:30 PDT 
655BADB18DA24B9F848F96891C4A0D8B 
Investigator Signature 
Investigator Name 
Date 
Research Centre Name 
On behalf of the International Partnership for Mcrobicides, I confirm that the sponsor will 
com ply with all obligations as detailed in all applicable regulations and guidelines. I will 
ensure that the investigator is informed of all relevant information that becomes available 
during the conduct of this trial. 
Chief fv1edical Officer Signature 
Annalene Nel, MBChB, PhD 
Chief fv1edical Officer Name (Printed) 
Date 
( 
DocuSigned by: 
I Annalene Nel 
V 
Signer Name: Annalene Nel 
L
Signing Reason: I approve this document 
Signing Time: 17-0ct-2019 I 09:30:42 EDT 
37B32E6FC322475BB4A116172FB6AC09 
Restricted* Confidential - Limited Access* 


17-Oct-2019 | 09:30:47 EDT
Desmond Tutu 
HIV 
Foundation
30-Oct-2019 | 01:36:17 PDT
Dr. K Gill
1PM 032 
Version 2.0 Amendment 4.0 
SIGNATURE PAGE 
1PM 032 
17 October 2019 
Page 2 of 3 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF 
AND ADHERENCE TO THE DAPNIRINE (25 mg) VAGINAL RING-004 IN 
HEAL THY, HIV-NEGATIVE WOMEN 
I have read this protocol and appendices and agree to conduct the trial as stipulated and 
in compliance with the principles of the World fv1edical Association Declaration of Helsinki, 
the 
International 
Council 
for 
Harmonisation 
of 
Technical 
Requirements 
for 
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines, and all 
a~
blei~lttiations and guidelines. 
I Dr. K Gill 
V 
Signer Name: Dr. K Gill 
L
Signing Reason: I approve this document 
Signing Time: 30-0ct-2019 I 01 :36:06 PDT 
3B43DA531C504637A872F8F25BBBE4F2 
Investigator Signature 
Investigator Name 
Date 
Research Centre Name 
On behalf of the International Partnership for Mcrobicides, I confirm that the sponsor will 
com ply with all obligations as detailed in all applicable regulations and guidelines. I will 
ensure that the investigator is informed of all relevant information that becomes available 
during the conduct of this trial. 
Chief fv1edical Officer Signature 
Annalene Nel, MBChB, PhD 
Chief fv1edical Officer Name (Printed) 
Date 
( 
DocuSigned by: 
I Annalene Nel 
V 
Signer Name: Annalene Nel 
L
Signing Reason: I approve this document 
Signing Time: 17-0ct-2019 I 09:30:42 EDT 
37B32E6FC322475BB4A116172FB6AC09 
Restricted* Confidential - Limited Access* 


17-Oct-2019 | 09:30:47 EDT
Dr. R Moraba
31-Oct-2019 | 08:59:41 PDT
Ndlovu 
Research 
Consortium
1PM 032 
Version 2.0 Amendment 4.0 
SIGNATURE PAGE 
1PM 032 
17 October 2019 
Page 2 of 3 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF 
AND ADHERENCE TO THE DAPNIRINE (25 mg) VAGINAL RING-004 IN 
HEAL THY, HIV-NEGATIVE WOMEN 
I have read this protocol and appendices and agree to conduct the trial as stipulated and 
in compliance with the principles of the World fv1edical Association Declaration of Helsinki, 
the 
International 
Council 
for 
Harmonisation 
of 
Technical 
Requirements 
for 
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) guidelines, and all 
apPft@S~ei~l!J~tions and guidelines. 
I Dr. R Moraba 
V 
Signer Name: Dr. R Moraba 
L
Signing Reason: I have reviewed this document 
Signing Time: 31-Oct-2019I08:59:23 PDT 
ED0F5463E4E543A0B363529CADE8D171 
Investigator Signature 
Investigator Name 
Date 
Research Centre Name 
On behalf of the International Partnership for Mcrobicides, I confirm that the sponsor will 
com ply with all obligations as detailed in all applicable regulations and guidelines. I will 
ensure that the investigator is informed of all relevant information that becomes available 
during the conduct of this trial. 
Chief fv1edical Officer Signature 
Annalene Nel, MBChB, PhD 
Chief fv1edical Officer Name (Printed) 
Date 
( 
DocuSigned by: 
I Annalene Nel 
V 
Signer Name: Annalene Nel 
L
Signing Reason: I approve this document 
Signing Time: 17-0ct-2019 I 09:30:42 EDT 
37B32E6FC322475BB4A116172FB6AC09 
Restricted* Confidential - Limited Access* 


IPM 032 
Version 2.0 Amendment 4.0 
17 October 2019 
Page 3 of 75
Restricted * Confidential – Limited Access* 
TABLE OF CONTENTS 
TABLE OF CONTENTS.......................................................................................................3 
ACRONYMS AND ABBREVIATIONS .................................................................................6 
PROTOCOL SYNOPSIS .....................................................................................................8 
1.
Introduction .................................................................................................................18 
1.1. 
Background .....................................................................................................18 
1.2. 
Dapivirine Vaginal Ring ..................................................................................19 
1.2.1. 
Dapivirine ..........................................................................................19 
1.2.2.Formulation of a Silicone Elastomer Matrix ring containing 25 mg of 
Dapivirine ............................................................................................................19 
1.3. 
Nonclinical Studies..........................................................................................19 
1.4. 
Clinical Trials ...................................................................................................21 
1.4.1. 
Phase I and II ....................................................................................21 
1.4.2. 
Phase III ............................................................................................22 
1.4.3. 
Adherence to and Acceptability of the Dapivirine Vaginal Ring.......23 
1.4.4. 
Condom Compatibility.......................................................................24 
1.5. 
Rationale for Protocol IPM 032.......................................................................24 
2.
Trial Objectives ...........................................................................................................25 
2.1. 
Trial Objectives ...............................................................................................25 
2.2. 
Trial Endpoints and Assessments ..................................................................25 
3.
Overall Trial Design ....................................................................................................27 
3.1. 
Trial Design .....................................................................................................27 
3.2. 
Trial Duration...................................................................................................27 
3.3. 
Trial Population ...............................................................................................27 
3.3.1. 
Inclusion Criteria – Women who Previously Enrolled in IPM 027 ....28 
3.3.2. 
Exclusion Criteria – Women who Previously Enrolled in IPM 027...28 
4.
Trial Visits and Procedures ........................................................................................28 
4.1. 
Screening Visit ................................................................................................28 
4.2. 
Enrolment Visit ................................................................................................30 
4.3. 
Trial Visits (Monthly research centre visits for the first one to three months, 
and 3-monthly research centre visits thereafter) ......................................................31 
4.4. 
Last Product Use Visit (LPUV) or Early Discontinuation Visit ........................32 
4.5. 
Exit Visit...........................................................................................................33 
4.6. 
Unscheduled Visits .........................................................................................34 
4.7. 
Missed and Late Visits ....................................................................................35 
4.8. 
Protocol Deviations .........................................................................................35 
4.9. 
Early Discontinuation Visits ............................................................................35 
4.10. Premature Discontinuation of the Trial ...........................................................36 
5.
Trial Procedure Details ...............................................................................................36 
5.1. 
Informed Consent ...........................................................................................36 
5.2. 
Comprehension Assessment Checklist ..........................................................38 
5.3. 
HIV Counselling ..............................................................................................38 
5.3.1. 
HIV Pre- and Post-test Counselling..................................................38 
5.3.2. 
HIV/STI Risk Reduction Counselling ................................................38 
5.4. 
HIV Testing and Management ........................................................................38 
5.4.1. 
Screening Visit ..................................................................................39 
5.4.2. 
Enrolment Visit ..................................................................................39 
5.4.3. 
Trial Visits and LPUV ........................................................................40 
5.4.4. 
Exit Visit.............................................................................................42 


IPM 032 
Version 2.0 Amendment 4.0 
17 October 2019 
Page 4 of 75
Restricted * Confidential – Limited Access* 
5.5. 
Contraceptive Counselling and Management of Contraception ....................43 
5.6. 
Pregnancy Testing and Management ............................................................43 
5.7. 
Demographics and Medical History................................................................44 
5.8. 
Physical Examination ......................................................................................44 
5.9. 
Pelvic Examination..........................................................................................44 
5.10. Laboratory testing for safety assessments and urine dipstick analysis .........45 
5.11. STI Testing and Management ........................................................................45 
5.11.1. 
STI Testing ........................................................................................45 
5.11.2. 
STI Management ..............................................................................46 
5.12. Cervical Cytology ............................................................................................46 
5.13. Vaginal Ring Dispensing.................................................................................46 
5.14. Vaginal Ring Insertion and Ring Removal......................................................47 
5.15. Vaginal Ring Adherence Counselling .............................................................47 
5.16. Qualitative Behavioural Assessments ............................................................47 
5.16.1. 
Participant Questionnaire .................................................................48 
5.17. Sample Storage and Analysis ........................................................................48 
5.18.Screening Identification (SCR-ID) and Participant Identification (PID) Numbers
...................................................................................................................................48 
5.19. Diary cards ......................................................................................................49 
5.20. Participant Reimbursement ............................................................................49 
5.21. Participant Compensation...............................................................................49 
5.22. Participant Responsibility................................................................................49 
5.23. Study Operations Manual (SOM) ...................................................................49 
6.
Investigational Product ...............................................................................................50 
6.1. 
Investigational Product Composition ..............................................................50 
6.2. 
Packaging and Labelling.................................................................................50 
6.3. 
Investigational Product Storage......................................................................50 
6.4. 
Investigational Product Administration ...........................................................50 
6.5. 
Investigational Product Expulsion or Loss......................................................51 
6.6. 
Retrieval of Investigational Product ................................................................51 
6.7. 
Investigational Product (IP) Accountability .....................................................52 
6.8. 
Concomitant Medications and Products .........................................................52 
7.
Adverse Events ..........................................................................................................52 
7.1. 
Definition .........................................................................................................52 
7.2. 
Assessment of Adverse Event Severity .........................................................53 
7.3. 
Relationship to Investigational Product ..........................................................53 
7.4. 
Serious Adverse Event ...................................................................................54 
7.4.1. 
Serious Adverse Event Definition .....................................................54 
7.4.2. 
Serious Adverse Event Contact Information ....................................55 
7.4.3. 
Sponsor Notification of SAEs to the Regulatory Authorities ............55 
7.4.4. 
Research Centre Notification of SAEs to Local Independent Ethics  
Committee or Local Health and Regulatory Authorities .....................................56 
7.5. 
Immediately Reportable Events......................................................................56 
7.6. 
Safety Monitoring ............................................................................................56 
7.7. 
Data Handling at Research Centres...............................................................56 
7.8. 
Source Data Verification .................................................................................57 
8.
Statistical Methods .....................................................................................................57 
8.1. 
Trial Endpoints ................................................................................................57 
8.2. 
Primary Trial Hypotheses ...............................................................................57 
8.3. 
Sample Size and Power Calculations ............................................................58 
8.4. 
Statistical Analyses .........................................................................................58 


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8.4.1. 
Primary Safety Analysis ....................................................................58 
8.4.2. 
Primary Adherence Analysis.............................................................58 
8.4.3. 
Secondary Analyses .........................................................................59 
8.4.4.Other results from Qualitative/Quantitative Behavioural assessments
.............................................................................................................................59 
8.4.5. 
Interim Analysis.................................................................................59 
8.5. 
Data and Safety Monitoring Board .................................................................59 
8.6. 
Handling of Missing Data and Dropouts .........................................................60 
9.
Investigator Requirements .........................................................................................60 
9.1. 
Trial Initiation ...................................................................................................60 
9.2. 
Institutional Review Boards or Independent Ethics Committee Approval .....60 
9.3. 
Trial Monitoring and Audits .............................................................................60 
9.4. 
Case Report Forms (CRFs) ............................................................................61 
9.5. 
Disclosure of Data...........................................................................................61 
9.6. 
Record Retention ............................................................................................61 
10. Ethical Considerations................................................................................................62 
10.1. Ethical Review.................................................................................................62 
10.2. Reporting and Management of Social Harms related to trial participation ....62 
10.3. Community Engagement ................................................................................62 
11. Publications ................................................................................................................63 
12. References .................................................................................................................64 
APPENDIX A: SCHEDULE OF PROCEDURES...............................................................66 
APPENDIX B: HIV TESTING ALGORITHM......................................................................69 
APPENDIX C: VISIT SCHEDULE AND APPROXIMATE BLOOD VOLUMES ................74 
APPENDIX D: TRIAL DESIGN ..........................................................................................75 


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ACRONYMS AND ABBREVIATIONS 
AE 
Adverse Event  
AIDS 
Acquired Immunodeficiency Syndrome  
ALT 
Alanine aminotransferase  
ARV 
Antiretroviral  
AST 
Aspartate aminotransferase  
AUC 
Area Under Plasma Concentration-time Curve  
BV 
Bacterial Vaginosis  
b.i.d.
“bis in die”/twice a day 
ºC
Degree Celsius 
CI
Confidence Interval 
CNS
Central Nervous System 
CRF
Case Report Form  
CT
Chlamydia Trachomatis 
DAIDS
Division of Acquired Immunodeficiency Syndrome  
DAPY 
Di-amino pyrimidine  
DSMB
Data and Safety Monitoring Board  
DVR
Dapivirine Vaginal Ring-004 
EC50
50% Effective Inhibition Concentration 
FBC
Full Blood Count  
FDA 
Food and Drug Administration (US)  
GCP
Good Clinical Practice  
HIV-1
Human Immunodeficiency Virus type 1 
Hu-SCID
Humanized Severe Combined Immunodeficient  
ICF
Informed Consent Form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IDI 
In-depth individual interview 
IEC 
Independent Ethics Committee  
IB 
Investigator’s Brochure 
IP 
Investigational Product 
IPM 
International Partnership for Microbicides  
IRB 
Institutional Review Board  
IRE 
Immediately Reportable Event  
ITT 
Intent-To-Treat 
LPUV 
Last Product Use Visit 
MedDRA 
Medical Dictionary for Regulatory Activities  
MTD 
Maximum Tolerated Dose  
MTN 
Microbicide Trials Network  
NAAT 
Nucleic Acid-Amplification Testing 
NG 
Neisseria Gonorrhoeae 
NGS 
Next Generation Sequencing 
NNRTI 
Non-nucleoside Reverse Transcriptase Inhibitor  
NOAEL 
No Adverse Effect Level 
PCR 
Polymerase Chain Reaction  
PID 
Participant Identification  
PMTCT 
Prevention of Mother-to-Child Transmission of HIV  
PEP 
Post-Exposure Prophylaxis 
PT 
Preferred Term 
RNA 
Ribonucleic Acid  


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RPR 
Rapid Plasma Reagin  
RT 
Reverse Transcriptase 
SAE 
Serious Adverse Event  
SAP 
Statistical Analysis Plan  
SCR-ID 
Screening Identification  
SOC 
System Organ Class 
SOM 
Study Operations Manual 
SOP 
Standard Operating Procedure 
STI 
Sexually Transmitted Infection 
TEAE 
Treatment Emergent Adverse Event  
TPHA 
Treponema Pallidum Haemagglutination Test  
TPPA 
Treponema Pallidum Particle Agglutination Assay 
TV 
Trichomonas Vaginalis 
UNAIDS 
Joint United Nations Programme on HIV/AIDS  
USA 
United States of America 
WHO 
World Health Organization 


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PROTOCOL SYNOPSIS 
IPM 032 
A FOLLOW-ON, OPEN-LABEL TRIAL TO ASSESS CONTINUED SAFETY OF AND 
ADHERENCE TO THE DAPIVIRINE (25 mg) VAGINAL RING-004 
IN HEALTHY, HIV-NEGATIVE WOMEN 
BACKGROUND:  
The Phase III clinical program of Dapivirine Vaginal Ring-004, 
containing 25 mg of dapivirine, consisted of the MTN-020 and 
IPM 027 clinical trials. These trials were conducted in South Africa, 
Uganda, Zimbabwe and Malawi, to assess the safety and efficacy 
of the Dapivirine Vaginal Ring-004 in preventing the acquisition of 
HIV-1 infection through male to female transmission during vaginal 
sexual intercourse in healthy, HIV-negative women. 
The results of the IPM 027 and MTN-020 trials demonstrated that 
the Dapivirine Vaginal Ring-004 is safe and reduced the risk of 
acquiring HIV-1 infection1,2. A lower HIV-1 risk reduction was 
observed in women ≤21 years of age in IPM 027 (the age effect was 
not statistically significant). Results were communicated to the 
relevant local and international regulatory authorities, IRBs/IECs, 
community representatives, participants and key stakeholders, as 
appropriate. 
IPM 032, a Phase IIIb follow-on trial to IPM 027, has been designed 
as an open-label clinical trial with the monthly Dapivirine Vaginal 
Ring (25 mg) to collect additional safety data and assess adherence 
to ring use in healthy, HIV-negative women with monthly (at least 
one to a maximum of three months) followed by 3-monthly research 
centre follow-up visits over 12 months. 
OBJECTIVES: 
The Primary Trial Objectives are: 
1. To assess the safety profile of the 25 mg Dapivirine Vaginal
Ring-004, when inserted at monthly intervals, in an open-label
trial
2. To assess adherence to the use of the 25 mg Dapivirine Vaginal
Ring-004 inserted at monthly intervals, in an open-label trial
The Secondary Trial Objectives are: 
1. To assess the incidence of HIV-1 seroconversion
2. To assess the frequency of HIV-1 drug resistance in women who 
acquire HIV-1 infection


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The Exploratory Trial Objectives are: 
1.
To assess the feasibility of 3-monthly follow-up visits, as a
possible schedule for post-licensure vaginal ring clinical
follow-up
2.
To explore the correlation between drug amount and results
from the visual inspection of the returned vaginal rings by
research staff between the monthly and 3-monthly research 
centre follow-up schedules
3.
To determine the proportion of participants electing to undergo
HIV rapid tests at the research centres between scheduled 
3-monthly visits
4.
To explore self-reported acceptability of and adherence to the
25 mg Dapivirine Vaginal Ring-004.
ENDPOINTS AND ASSESSMENTS:  
The primary endpoints are: 
1.
Safety
•
All Adverse Events (AEs) assessed by the investigator to
be related to the Dapivirine Vaginal Ring-004
•
All Grade 3 and 4 AEs
•
All Serious Adverse Events (SAEs)
2.
Adherence
•
Residual amounts of dapivirine in returned rings; and/or
dapivirine concentrations in plasma and/or dapivirine
concentrations in vaginal fluid
The primary endpoints will be assessed through: 
1.
Safety
•
All product-related AEs, Grade 3 or 4 AEs, SAEs, physical
examination, 
gynaecological 
assessments, including
pelvic/speculum examination, laboratory tests and other
indicated investigations
2.
Adherence
•
Determined dapivirine residual amounts in returned used
vaginal rings and/or
•
Measured concentrations of dapivirine in plasma and/or
•
Measured concentrations of dapivirine in vaginal fluids


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The secondary endpoints are: 
•
The HIV-1 seroconversion rate per 100 woman-years of
product use at the end of the vaginal ring use period
•
HIV-1 drug resistance mutations among participants who
acquire HIV-1 infection
The secondary endpoints will be assessed through: 
•
Rapid and specialised laboratory testing according to a
pre-specified HIV testing algorithm
•
Viral genotype (including NGS) and phenotype resistance
testing methods which include sensitive methods to detect
low frequency drug-resistant variants
The exploratory endpoints are: 
•
Feasibility of 3-monthly clinical follow-up schedule
•
Dapivirine residual amounts in returned used vaginal rings
and/or dapivirine concentrations in blood and/or vaginal
fluid in correlation with results from the visual inspection of
the returned used vaginal rings by research staff
•
Proportion of participants opting for HIV rapid tests at the
research centre between scheduled 3-monthly research
centre follow-up visits
•
The proportion of women who report the use of the vaginal
ring as acceptable
•
Participant self-reported patterns of ring use
The exploratory endpoints will be assessed through: 
•
Participant report of feasibility regarding a 3-monthly
clinical follow-up schedule (Participant Questionnaire)
•
Number of women opting not to receive two additional rings
at the 3-monthly visits
•
Proportion of returned rings (used and unused) during the
3-monthly clinical follow-up schedule
•
Dapivirine residual amounts in returned used vaginal rings
and/or dapivirine concentrations in blood and/or vaginal
fluid
•
Visual inspection of the returned used vaginal rings by
research centre staff
•
Number of participants undergoing HIV rapid tests at the
research centre between scheduled 3-monthly research


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centre follow-up visits 
•
Qualitative data regarding reasons for ring acceptability
and self-reported patterns of ring use
TRIAL DESIGN:  
IPM 032 is a Phase IIIb, multi-centre follow-on open-label trial to 
evaluate the continued adherence to and safety of the Dapivirine 
Vaginal Ring-004 inserted at monthly intervals in healthy, HIV-
negative women who have participated in the IPM 027 Phase III 
Dapivirine Vaginal Ring-004 trial. All women who have participated 
in IPM 027 and are HIV-negative at screening for IPM 032 will be 
eligible. An estimate of up to 1400 participants will be enrolled. 
All participants will attend a research centre follow-up visit one 
month after enrolment. Following this visit, at the investigator’s 
discretion, a participant can continue on a 3-monthly visit schedule. 
Monthly visits may however be extended up to the first three months 
of participation. Once the 3-monthly trial visit schedule commences, 
three rings will be dispensed to the participant. One ring will be self-
inserted at the research centre and two additional rings will be 
dispensed for the participant to take home, or dispensing will take 
place as arranged with the participant.  
TRIAL DURATION: Each participant will engage in the screening process for up to 
45 days prior to enrolment and will use the Dapivirine Vaginal 
Ring-004 for a period of up to 12 months. IPM will have the option 
to extend this trial period. Accrual will take place over approximately 
6 months and those participants who are enrolled more than 
6 months after the onset of the trial site’s accrual period may have 
a shortened follow-up period. 
Each participant will have an exit visit approximately 1-2 months 
after ring discontinuation, to assess safety and identify HIV 
seroconversions after product discontinuation.  
POPULATION AND SAMPLE SIZE: 
Up to 1400 HIV-negative women who have participated in the IPM 
027 Phase III Dapivirine Vaginal Ring-004 trial, who understand the 
trial and can provide informed consent are expected to enrol in this 
open-label trial.  
INCLUSION CRITERIA – WOMEN PREVIOUSLY ENROLLED IN IPM 027: 
Women must meet all of the following criteria to be eligible for trial 
enrolment: 
1.
Previously enrolled in the IPM 027 trial
2.
Available for all visits and consent to follow all procedures
scheduled for the trial
3.
Using an effective method of contraception at the


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Enrolment Visit, and intending to use an effective 
contraceptive method for the duration of trial participation, 
unless post-menopausal with no history of menses for one 
year prior to screening  
4.
HIV-negative as determined by the HIV algorithm applied
at Screening/Pre-Enrolment
5.
Willing to refrain from participation in another research trial
using drugs, vaccines, medical devices and microbicides
for the duration of the IPM 032 trial
6.
Willing to provide adequate locator information for trial
retention purposes and be reachable per local standard
procedures (e.g. by home visit or telephone; or via family
or close neighbour contacts); confidentiality to be
maintained
EXCLUSION CRITERIA – WOMEN PREVIOUSLY ENROLLED IN IPM 027: 
Women who meet any of the following criteria are NOT eligible to 
enrol in the trial: 
1.
Investigational product use permanently discontinued in
response to an AE (where the AE was considered related
to investigational product) or safety-related concern while
taking part in the IPM 027 trial
2.
Currently pregnant, intending to become pregnant, or
currently breast-feeding
3.
Known drug abuse or alcohol dependence in the
12 months prior to screening
4.
Participated in another research trial (other than IPM 027)
using drugs, medical devices, microbicides or oral pre-
exposure prophylaxis agents within 30 days prior to
screening
5.
Any new illness or condition(s), chronic condition(s) or
abnormal laboratory finding(s) that, in the opinion of the
investigator, might put the participant at risk, or interfere
with the trial objectives or the participant’s adherence to
trial requirements
METHODS: 
Screening Visit: 
Potential participants who are HIV-negative, who participated in 
IPM 027 and who provide informed consent will be invited to screen 
for the trial and to enrol in the open-label follow-on trial. After 
informed consent is obtained, a SCR-ID number will be assigned to 
each potential participant for identification purposes and the 
potential participant will be screened to assess eligibility for the trial. 
A comprehension checklist will be used to support the informed 
consent process. 


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At screening, potential participants will provide information on 
inclusion and exclusion criteria, including locator and basic menses 
information, 
demographic 
information, 
and 
medical 
and 
concomitant medication history. Each potential participant will 
receive a general physical examination and pelvic examination.  
All potential participants will be provided with HIV/STI risk-reduction 
counselling (including provision of male and/or female condoms, 
should participants wish to receive them), contraceptive counselling 
and HIV pre- and post-test counselling. Contraceptives will be 
provided if necessary, as well as treatment and/or referral for 
sexually transmitted infections (STIs) and other findings as 
necessary. Safety laboratory assessments, urine dipstick analysis 
(microscopy only if clinically indicated), cervical sample collection 
for cytology and testing for pregnancy, HIV, STIs, and syphilis will 
be performed. Blood samples for HIV-1 RNA PCR, HIV viral 
genotype (including NGS) and phenotype resistance testing will be 
collected and stored for retrospective testing subsequent to a 
confirmed HIV-1 seroconversion. 
Enrolment Visit: 
At the Enrolment Visit, potential participants will provide information 
on inclusion and exclusion criteria, including locator and basic 
menses information, and medical and concomitant medication 
history. AEs (post-enrolment) and the occurrence of possible social 
harms will be assessed. 
All potential participants will be provided with HIV/STI risk-reduction 
counselling (including provision of male and/or female condoms, 
should participants wish to receive them), contraceptive counselling 
and provision of contraceptives (if necessary), HIV pre- and post-
test counselling and vaginal 
ring adherence counselling. 
Participants will be provided with feedback on the IPM 027 and 
MTN-020 trial results. Diary cards will be issued with instructions for 
completion. 
Testing for pregnancy and HIV will be performed. Blood samples 
will be collected for storage, and HIV-1 RNA PCR, HIV viral 
genotype (including NGS) and phenotype resistance testing will be 
performed retrospectively 
subsequent to confirmed HIV-1 
seroconversion.  
Eligible women will be assigned a unique PID number. Each 
participant will be provided with vaginal ring use and storage 
instructions and instructed to self-insert a newly dispensed vaginal 
ring.  
Trial Visits: 
All participants will provide information on concomitant medication, 
locator details and menses. Participants will receive pre- and post-
test HIV counselling; HIV/STI risk reduction counselling; vaginal 


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ring adherence counselling; HIV rapid testing and pregnancy 
testing. Male and/or female condoms will be provided at all visits, 
should participants wish to receive them, as part of HIV/STI risk 
reduction 
counselling. 
Contraceptive 
counselling 
and 
contraceptives (if needed) will be provided at all visits. Possible 
occurrence of social harms will be assessed during research centre 
visits.  
Blood samples will be collected for storage at each trial visit and will 
be tested retrospectively by HIV-1 RNA PCR, HIV viral genotype 
(including NGS) and phenotype resistance testing subsequent to 
confirmed HIV seroconversion. At the point of HIV seroconversion, 
vaginal ring use will be discontinued, and in addition, blood samples 
for viral genotype (including NGS) and phenotype resistance will be 
collected at the scheduled exit visit, 1-2 months following 
seroconversion.  
Blood and vaginal fluid samples will be collected for possible 
measurement of dapivirine concentrations. Returned rings will be 
visually inspected by research centre staff and may also be 
analysed for residual amounts of dapivirine. Results may be shared 
with participants to support ring-use adherence counselling. 
Returned diary cards will be reviewed and new diary cards issued 
to participants as applicable. Each participant will be asked to 
complete a Participant Questionnaire at every trial visit. AEs will be 
assessed at all visits post-enrolment. In addition, if clinically 
indicated, safety laboratory assessments, urine dipstick analysis 
(microscopy only if clinically indicated), pelvic examinations, 
cervical sample collection for cytology, physical examinations and 
STI tests will be performed. Treatment and/or referral for STIs and 
other findings may be performed, if required. 
At each trial visit, participants will return used vaginal rings and each 
participant will be instructed to self-insert a newly-dispensed vaginal 
ring and be provided with vaginal ring use and storage instructions. 
Two additional rings will be dispensed once participants commence 
with the 3-monthly trial visit schedule, which the participants should 
self-insert at monthly intervals, at home, until the next Trial Visit. 
Participants who prefer not to have additional vaginal rings in their 
possession may also choose to return and to collect the vaginal 
rings from the research centre at time intervals suitable to them, 
providing a new ring is inserted monthly. HIV rapid tests will be 
offered to participants during these interim visits.  
If a participant is unable to attend the next scheduled visit, the 
investigator or designee could dispense additional ring(s) on a 
case-by-case basis. All such circumstances must be documented 
fully by the investigator or designee as described in the IPM 032 
Study Operations Manual (SOM). If a participant requires an 


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additional ring at a time other than when they are scheduled to 
receive one, they will be required to attend the clinic for an interim 
visit. 
Last product use visit (LPUV): 
At the last product use visit, participants will return any used/unused 
rings; report any medical problems, social harms and concomitant 
medications since the last visit; provide locator and basic menses 
information; 
receive 
pre- 
and 
post-test HIV 
counselling, 
contraceptive counselling and HIV/STI risk-reduction counselling 
(including provision of male and/or female condoms, should 
participants wish to receive them); undergo a physical examination 
as well as a pelvic examination; be tested for STIs, pregnancy and 
HIV; and may undergo safety laboratory assessments, urine 
dipstick analysis (microscopy only if clinically indicated) and cervical 
sample collection for cytology (if no result is evident within the 
previous year, or abnormal at last cervical cytology). Contraception 
and STI treatment will be provided or participants will be referred, if 
needed. Blood samples will be collected for storage, and will be 
tested retrospectively by HIV-1 RNA PCR, HIV viral genotype 
(including NGS) and phenotype resistance testing subsequent to 
confirmed HIV seroconversion. Blood and vaginal fluid samples 
may be collected for measurement of dapivirine concentrations. 
Returned rings will be visually inspected by research centre staff 
and may also be analysed for residual amounts of dapivirine. 
Returned diary cards will be reviewed. Participants will be asked to 
complete a Participant Questionnaire.  
Exit visit - approximately 1-2 months after ring discontinuation:  
On the day of the scheduled exit visit, participants will return to the 
research centre to receive results from their STI testing and safety 
laboratory assessments performed at the last product use visit, if 
applicable, and receive treatment or referral as needed. AEs, 
concomitant medications and possible social harms will be 
recorded at this visit. 
Participants will receive pre- and post-test counselling for HIV and 
undergo HIV testing. HIV/STI risk reduction counselling (including 
provision of male and/or female condoms, should they wish to 
receive them) and contraceptive counselling will also be provided 
at the exit visit. Contraception and STI treatment will be provided or 
the participant will be referred, if needed. The following procedures 
are not required, but may be conducted if clinically indicated: 
physical and pelvic examination, cervicovaginal sample collection 
for STI testing, provision of treatment and/or referral for STIs and 
other findings, laboratory testing for safety assessments, urine 
dipstick analysis (microscopy only if clinically indicated), and 
cervical sample collection for cytology (if no result is evident within 
the previous year, or abnormal at last cervical cytology). Blood 
samples will be collected for storage, and will be tested 
retrospectively by HIV-1 RNA PCR, HIV viral genotype (including 


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NGS) and phenotype resistance testing subsequent to confirmed 
HIV seroconversion. 
Participants will then be considered to have completed trial 
participation. 
Qualitative and Quantitative Behavioural Assessments: 
In cases of interest in-depth interviews (IDIs) will be conducted; 
approximately three participants will be interviewed per site. These 
cases of interest may include, but will not be limited to participants 
who may have experienced social harms, may have had problems 
using the ring, or who HIV seroconverted. 
These assessments will provide data on acceptability and 
influencers of ring use. The recruitment and sampling strategy will 
be specified in the study operations manual. 
STATISTICAL CONSIDERATIONS: 
Sample Size: 
This is an open-label, follow-on trial to IPM 027 to evaluate the 
safety of and adherence to Dapivirine Vaginal Ring-004, inserted at 
monthly intervals in healthy, HIV-negative women who have 
participated in the IPM 027 trial. No formal sample size or power 
calculations have been performed. 
It is expected that up to 70% of the participants enrolled in IPM 027 
will participate in this trial. Therefore, a total sample size of up to 
1400 HIV-negative women is anticipated.  
Statistical Analyses: 
The primary analysis will focus on safety as well as adherence 
assessments, performed under the intent-to-treat (ITT) principle. As 
it is possible that the inclusion of non-adherent participants or 
participants who discontinued from ring use may artificially lower 
the rates of safety outcomes, additional analyses will be conducted 
on the per-protocol population, which will include only participants 
who were adherent to the protocol. 
A descriptive analysis of all AEs will be presented in tables and 
listings. AEs will be summarised by MedDRA System Organ Class 
(SOC) and Preferred Term (PT). The proportion of participants 
experiencing 
adverse events, including 
the proportion of 
participants experiencing product-related adverse events, Grade 3 
or 4 AEs, or SAEs, will be determined, and presented with 
corresponding 95% confidence intervals (CIs). 
Residual levels of dapivirine in returned rings, and/or plasma and/or 
vaginal fluid concentrations of dapivirine will be used as measures 
of adherence to ring use. The data will be listed, summarised and 


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presented graphically. The ring residual levels and/or plasma 
and/or vaginal fluid concentrations of dapivirine associated with 
non-adherence will be informed by the results from IPM 027, and 
will be described in detail in the SAP, which will be finalised prior to 
final database lock. The correlation between the amount of residual 
dapivirine in the used rings and the corresponding plasma and/or 
vaginal fluid levels of dapivirine will be explored graphically and 
summarised descriptively. 
For the secondary analysis, the number of HIV-1 seroconversions, 
the incidence density rate of HIV-1 seroconversion, i.e. HIV-1 
seroconversion rate per 100 woman-years of product use at the end 
of the ring use period, as well as a 95% confidence interval for the 
HIV-1 seroconversion rate per 100 woman-years based on the 
normal approximation of the Poisson distribution will be presented 
for each research centre and overall. Kaplan-Meier curves will also 
be presented, overall and by research centre. The analysis of HIV-
1 drug resistance will be primarily descriptive in nature, and will 
depend on the pattern of resistance mutations observed in the 
HIV-1 seroconverters. A frequency tabulation of individual 
resistance mutations associated with the various classes of 
antiretrovirals, e.g. Protease Inhibitors, Nucleoside Reverse 
Transcriptase 
Inhibitors 
and 
Non-nucleoside 
Reverse 
Transcriptase Inhibitors, will be produced. The proportion of HIV-1 
seroconverters with at least one HIV-1 drug resistant mutation will 
be presented, with the corresponding 95% CI. 
Appropriate statistical analyses of the exploratory endpoints will be 
performed. 
Full details of the planned statistical analyses will be provided in a 
Statistical Analysis Plan (SAP) that will be finalised before final 
database lock. 


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1. Introduction
1.1.
Background 
Women continue to be affected disproportionately by HIV in sub-Saharan Africa, where 
they account for 58% of people living with HIV3. It is estimated that every hour, around 
19 young women are newly infected with HIV4. Unprotected heterosexual intercourse is 
currently the leading mode of HIV acquisition among women. Correct and consistent use 
of latex condoms is one proven method of preventing HIV acquisition. However, many 
women are unable to negotiate condom use with their partners. Physiologically, women 
are more likely than men to acquire HIV during heterosexual intercourse, and young girls 
are most vulnerable5. In sub-Saharan Africa, the number of new HIV infections among 
adolescent girls and young women aged 15-24 years remains exceptionally high, with 
approximately 8600 new infections per week6. These females are at least twice as likely 
to be infected with HIV as their male peers7. The United Nations (UN) Political Declaration 
on Ending AIDS adopted in June 2016 calls for reducing new HIV infections among 
adolescent girls and young women aged 15-24 years to fewer than 100,000 per year by 
20208. Achieving this target demands dramatic acceleration of action and expanding of 
programs for adolescent girls and young women, as gender inequities often render women 
unable to abstain from sex or negotiate condom use with partners, a proven method of 
preventing HIV acquisition. Most current HIV prevention methods require the consent (as 
well as some action or behaviour change) of the male partner9. Therefore, the ongoing 
development of safe and effective HIV prevention technologies that can be made easily 
accessible to developing countries remains a public health priority.  
Developing HIV prevention options that women can use therefore remains a global 
challenge. Antiretroviral (ARV) approaches to prevention have the potential to transform 
the response to the HIV/AIDS pandemic. For women, further research is needed on 
microbicides that contain different ARV compounds in different formulations and dosing 
strategies, in order to provide various options for HIV prevention. Vaginal microbicides, 
which are self-initiated, could offer women a critically needed new tool to prevent HIV, 
especially for those women who are not able to negotiate mutual monogamy or condom 
use10. ARV-based microbicides can be formulated in a number of dosage forms that allow 
them to be used in a variety of ways, such as around the time of sex, or daily or monthly, 
independent of sexual activity.  
In order for a microbicide to be most effective, it is essential that it is used correctly and 
consistently, and is acceptable to women and their male partners. A product used 
independently of sexual intercourse could be more convenient for women and provide 
long-term protection during anticipated and unanticipated sexual intercourse. Vaginal 
rings that need monthly replacement may therefore have benefits. The Dapivirine Vaginal 
Ring-004 has completed Phase III clinical development. 
The results from two Phase III trials of the Dapivirine Vaginal Ring-004, The Ring Study 
(IPM 027) and ASPIRE (MTN- 020) were announced at the Conference on Retroviruses 
and Opportunistic Infections (CROI in Boston, MA) in February 2016. Both trials 
demonstrated that the Dapivirine Vaginal Ring-004 was well-tolerated and prevented 
HIV-1 infection in approximately one in three women between the age of 18-45 years 
overall, a statistically significant result (p<0.05 in both trials1,2,11,12). Post-hoc data analyses 
provide supportive evidence that Dapivirine Vaginal Ring-004 risk reduction of HIV-1 
increases when adherence increases. The ASPIRE trial showed that women who 


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appeared to use the ring more consistently (defined as at least 3 mg of dapivirine released 
from the ring during 4 weeks of continuous use) had at least a 65% reduction in risk, and 
additional subgroup analyses of women who appeared to use the ring most consistently 
suggest 75% or more reduction in risk13. Similarly, in a post-hoc analysis of The Ring Study 
data, 65% efficacy was seen in women who appeared to use the Dapivirine Vaginal 
Ring-004 more consistently11. A lower HIV-1 risk reduction was observed in women 
≤21 years of age in IPM 027 (the age effect was not statistically significant). In ASPIRE, 
age was shown to be significantly related to HIV-1 protection, with no protection observed 
in participants aged 18-21 years, and 56% protection in participants over 21 years of 
age2,12. Further research is needed to understand younger women’s unique challenges in 
using HIV prevention methods, as well as exploring dapivirine vaginal ring-use in the 
context of known safety and efficacy and if it would increase the HIV risk reduction 
demonstrated in the Phase III trials.  
1.2. 
Dapivirine Vaginal Ring 
1.2.1. Dapivirine 
Dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is a di-amino-
pyrimidine (DAPY) derivative with the chemical name 4-[[4-[(2,4,6-trimethylphenyl)amino]-
2-pyrimidinyl]amino] benzonitrile. NNRTIs bind directly to the HIV reverse transcriptase
(RT) enzyme, preventing viral replication. Dapivirine was originally developed by Janssen 
Research and Development (formerly Tibotec Pharmaceuticals) as an oral antiretroviral
compound and was tested in Phase I and II clinical trials in more than 200 participants. 
Although first conceived as an oral therapeutic, dapivirine is a promising candidate for
development as a topical microbicide due to its proven in vitro and in vivo efficacy and
favourable safety profile as well as its physical and chemical properties. Dapivirine has
potent activity against wild-type HIV-1 strains and strains harbouring different resistance-
inducing mutations. Dapivirine’s antiretroviral profile is superior to that of earlier NNRTI
class compounds such as nevirapine, delavirdine, and efavirenz. In vitro tests have shown 
that dapivirine is inactive against HIV-2 and has no efficacy against common sexually
transmitted infections. Dapivirine is therefore not intended to protect against HIV-2 or other
sexually transmitted infections, nor does it have any contraceptive properties.
1.2.2. Formulation of a Silicone Elastomer Matrix ring containing 25 mg of 
Dapivirine 
The dapivirine silicone elastomer vaginal matrix ring (Ring-004) is an off-white flexible ring 
containing 25 mg of dapivirine dispersed in a platinum-catalysed silicone matrix. The 
dimensions of the ring are 56 mm (outer diameter) and 7.7 mm (cross-sectional diameter). 
Details regarding the formulation and dimensions are provided in the Dapivirine Vaginal 
Ring-004 Investigator’s Brochure (IB)14. The dapivirine vaginal ring is designed to provide 
sustained release of dapivirine for a minimum of one month. 
1.3. 
Nonclinical Studies 
The potential of dapivirine as a microbicide for prevention of sexual transmission of HIV 
has been assessed in a variety of in vitro, ex vivo and in vivo models. Furthermore, a 
comprehensive program of preclinical studies was used to evaluate the toxicity of 
dapivirine. The studies are described in the IB14. 


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Virology: 
The activity of dapivirine against wild-type HIV-1, African isolates of HIV-1 (including 
subtype C virus), and a panel of NNRTI-resistant viruses has been established using in 
vitro models, with EC50 values ranging from 0.3 ng/mL (0.9 nM) against laboratory isolates 
to < 33 ng/mL (< 100 nM) for HIV-1 isolates encoding one or more known NNRTI 
resistance mutations. The anti-HIV activity was also confirmed in an ex vivo model of 
human cervical explant cultures and in an in vivo humanized severe combined 
immunodeficient (hu-SCID) mouse model. 
Nonclinical safety pharmacology: 
In a series of preclinical safety pharmacology studies, dapivirine was generally devoid of 
adverse effects on overt behaviour, reflexes and other body functions. Although safety 
pharmacology studies revealed no cardiovascular effects, there was evidence of an 
increase in QT interval during the 4- and 6-month oral toxicity study in dogs. However, this 
was only seen at ≥ 30 mg/kg/day, at which Cmax and AUC values were respectively more 
than 3800 and 2500 times the values achieved in women following use of the Dapivirine 
Vaginal Ring-004. 
Nonclinical pharmacokinetics: 
Systemic exposure to dapivirine was low following vaginal administration of dapivirine gels 
to rabbits. Much higher systemic exposures were obtained in single dose oral and 
subcutaneous toxicity studies in mice and rats, and in repeat dose oral toxicity studies in 
rats, dogs and monkeys. The free fraction of dapivirine in plasma was 0.19-0.34% in the 
male rat, 0.18-0.39% in the female rat, 0.21–0.22% in the dog and 0.15% in man. In rats, 
tissue to plasma AUC0-24 ratios following a single oral dose were 11 in liver, 7-8 in lung, 
kidney and adrenals, about 4 in spleen and lymph nodes, and 2-3 in brain, heart and 
muscle. Plasma/tissue equilibrium was rapid, and there was no undue retention of 
dapivirine in tissues.  
For virtually all tissues, maximal concentrations after vaginal dosing were < 1% of those 
after oral dosing. Preliminary metabolism studies demonstrated the presence of free and 
conjugated metabolites in rats, dogs, monkeys and humans, but the molecular structures 
have not been elucidated. There was evidence of extensive cytochrome P450 (particularly 
CYP3A4) mediated metabolism. 
Nonclinical toxicology: 
Dapivirine has been investigated in single and repeat dose toxicity studies, in a range of 
reproductive toxicity and mutagenicity studies, and in a carcinogenicity study. In vaginal 
studies in rabbits there were no significant local or systemic findings following repeat 
administration at up to 20 mg/mL for 14 days, up to 5 mg/mL for 13 weeks or up to 2 mg/mL 
for 39 weeks, or in reproductive toxicity studies in rats and rabbits performed at 
concentrations up to 2 mg/mL (0.2%). In a 13-week study in sheep using Ring-004, there 
was no evidence of local or systemic toxicity. 
The no adverse effect level (NOAEL) in rats and dogs following oral administration was 
20 mg/kg/day. At higher dose levels, hepatotoxicity was observed in dogs and slight 
hematological and clinical chemistry changes were observed in rats. The NOAEL in oral 
reproductive toxicity studies in the rat was also 20 mg/kg/day, whereas in the rabbit no 
effects were seen at dosages up to 90 mg/kg/day. Dapivirine was considered to be non-
genotoxic. In the guinea pig, dapivirine (2 mg/mL) did not demonstrate any potential to 


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cause contact sensitization. No treatment-related neoplastic or non-neoplastic findings 
were seen in a vaginal carcinogenicity study in rats at concentrations up to 5 mg/mL. 
1.4. 
Clinical Trials 
Multiple clinical trials have evaluated the safety of dapivirine in different formulations. 
Below is a summary of the data collected through these studies. More detailed information 
is available in the Dapivirine Vaginal Ring-004 IB14.  
Across all clinical trials with multiple ring configurations in healthy participants, the 
dapivirine vaginal ring was generally safe and well tolerated. No drug-related serious 
adverse events (SAEs) have been reported to date and no trials were stopped for safety 
reasons. In completed trials of Dapivirine Ring-004, one participant assigned to Dapivirine 
Ring-004 required permanent discontinuation of the investigational product due to a non-
serious adverse event considered by the investigator as possibly related to product use. 
This event, a Grade 2 (moderate intensity) generalized pruritus, required action taken by 
the Investigator to discontinue IP use permanently as a direct result of the event. Three 
SAEs were reported in dapivirine ring users (Ring-004) and six SAEs in placebo ring users. 
The Phase III clinical development program for the Dapivirine Vaginal Ring-004 included 
two pivotal trials, IPM 027 and MTN-020, which evaluated long term safety and efficacy of 
Dapivirine Vaginal Ring-004 compared to a placebo vaginal ring in 4588 participants 
(2620 enrolled to the dapivirine ring and 1968 enrolled to the placebo ring). No safety 
concerns or clinically relevant differences in safety parameters were observed between 
treatment groups. No SAEs were considered related to the use of dapivirine or placebo 
vaginal rings in either trial. 
1.4.1. Phase I and II 
To date (16 January 2017), 27 Phase I and Phase I/II clinical trials of dapivirine have been 
completed: 8 trials of dapivirine vaginal rings in 469 participants (298 using dapivirine rings 
and 183 using placebo rings); 8 trials of dapivirine vaginal gel in 774 participants (491 
using dapivirine gel and 283 using placebo gel); and 11 trials of oral dapivirine in which a 
total of 211 participants used oral dapivirine. Two Phase I clinical trials that evaluated a 
vaginal film formulation of dapivirine in 71 women have been conducted.  In addition, one 
Phase I clinical trial in male participants to assess the safety and tolerability of a dapivirine 
vaginal gel, following multiple topical penile exposures, was conducted in 48 healthy, 
HIV-negative, adult males, 24 of whom were circumcised and 24 uncircumcised 
(MTN-012/IPM 010). The dapivirine gel formulation was well tolerated by the participants. 
No SAEs or discontinuations due to TEAEs were reported during this trial. 
Based on information in the current IB14, across all completed Dapivirine Ring-004 trials 
(IPM 024, IPM 013, IPM 015, IPM 028 and IPM 034), the most commonly occurring TEAEs 
that were documented in at least 5% of participants in dapivirine versus placebo treated 
participants (n=259 using dapivirine rings and n=160 using placebo rings, respectively) 
were metrorrhagia (29.7% vs 24.4%), headache (15.1% vs 11.9%), gynaecological 
chlamydia infection (8.5% vs 13.4%), vaginal candidiasis (8.1% vs 7.5%), urinary tract 
infection (6.9% vs 8.8%), vaginal discharge (6.6% vs 6.3%), upper respiratory tract 
infection (5.8% vs 10.0%) and lower abdominal pain (5.4% vs 5.0%). 


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1.4.1.1. 
Oral Dapivirine 
There have been 11 oral administration trials in which a total of 211 participants have been 
dosed with dapivirine. The maximum tolerated dose (MTD) established was 350 mg for a 
single dose, and for multiple doses, 300 mg b.i.d. for 14 days. There were no deaths during 
the clinical trials of oral dapivirine, and no trials were stopped for safety reasons. A total 
of 10 participants stopped dapivirine treatment prior to trial completion for safety reasons, 
6 of whom stopped due to a clear dose-dependent increase in central nervous system 
(CNS) and gastrointestinal TEAEs, thereby establishing the MTD at 300 mg b.i.d. These 
TEAEs resolved within 1-2 days after discontinuation of use of oral dapivirine.  
Adverse events documented in 5 or more participants (> 2%) after oral exposure to 
dapivirine were headache, dizziness, nausea, diarrhoea, fatigue, tremor, somnolence, 
flatulence, and vomiting. Most (≥ 80%) of these TEAEs were Grade 1 or 2 (mild or 
moderate) and most (≥ 80%) were considered to be related to dapivirine. Grade 3 (severe) 
TEAEs included headache, dizziness, injury, nausea, tremor, paraesthesia, disturbance 
in attention, abrasion, AST increased, ALT increased, polyuria, fever, diarrhoea, and 
vomiting. The increases in AST and ALT were transient and the Grade 3 increases in AST 
and ALT occurred in a single participant who received 50 mg oral dapivirine as a twice 
daily dose.  
1.4.2. Phase III 
The Phase III clinical program of the dapivirine vaginal ring, containing 25 mg of dapivirine 
(Ring-004), consisted of the MTN-020 and IPM 027 clinical trials. These trials were 
conducted in South Africa, Uganda, Zimbabwe and Malawi, to assess the safety and 
efficacy of the Dapivirine Vaginal Ring-004 in preventing the acquisition of HIV-1 infection 
through male to female transmission in healthy, HIV-negative women.  
IPM 027 was a double-blind, multi-centre, placebo-controlled trial that was designed to 
assess the safety and efficacy of the Dapivirine Vaginal Ring-004, inserted once every 
4 weeks over a period of 24 months, in healthy, sexually active HIV-negative women, 18 
to 45 years of age, when compared to a placebo vaginal ring. It was conducted at 7 
research centres, six in South Africa and one in Uganda. A total of 1959 eligible women 
were randomized in a 2:1 ratio to receive either the dapivirine vaginal ring or placebo 
vaginal ring. Of these, 1307 women were enrolled in the dapivirine ring group and 652 
women in the placebo ring group. This trial was initiated in March 2012 and an early 
primary efficacy analysis was initiated in November 2015 to align with the publication of 
the MTN-020 data (see below).  
MTN-020 was designed to assess the safety and effectiveness of the Dapivirine Vaginal 
Ring-004, inserted once every 4 weeks, in healthy, sexually active, HIV-negative women, 
18 to 45 years of age, when compared to a placebo vaginal ring. It was conducted in 
Malawi, South Africa, Uganda and Zimbabwe. A total of 2629 women were randomized. 
Each participant was to use the investigational product until 120 events (HIV-1 
seroconversions) were observed in the trial. All participants were to use the investigational 
product for a minimum of 12 months. The trial was initiated in August 2012 and clinical 
conduct completed in June 2015.  
The results from two Phase III trials of the Dapivirine Vaginal Ring-004, The Ring Study 


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(IPM 027) and ASPIRE (MTN-020) were announced at the Conference on Retroviruses 
and Opportunistic Infections (CROI in Boston, MA) in February 2016. Both trials 
demonstrated that the Dapivirine Vaginal Ring-004 was well-tolerated and prevented 
HIV-1 infection in approximately one in three women between the age of 18-45 years 
overall, a statistically significant result (p<0.05 in both trials1,2,11,12). Post-hoc data analyses 
provide supportive evidence that Dapivirine Vaginal Ring-004 risk reduction of HIV-1 
increases when adherence increases. The ASPIRE trial showed that women who 
appeared to use the ring more consistently (defined as at least 3 mg of dapivirine released 
from the ring during 4 weeks of continuous use) had at least a 65% reduction in risk, and 
additional subgroup analyses of women who appeared to use the ring most consistently 
suggest 75% or more reduction in risk13. Similarly, in a post-hoc analysis of The Ring Study 
data, 65% efficacy was seen in women who appeared to use the Dapivirine Vaginal 
Ring-004 more consistently11. A lower HIV-1 risk reduction was observed in women ≤21 
years of age in IPM 027 (the age effect was not statistically significant). In ASPIRE, age 
was shown to be significantly related to HIV-1 protection, with no protection observed in 
participants aged 18-21 years, and 56% protection in participants over 21 years of age2,12. 
1.4.3. Adherence to and Acceptability of the Dapivirine Vaginal Ring 
IPM 011 was an open-label, crossover trial conducted in South Africa and Tanzania 
among sexually active women to assess the safety and acceptability of a silicone 
elastomer placebo vaginal ring (containing no active ingredient), intended as a microbicide 
delivery method for the prevention of HIV infection. Participants were randomly assigned 
in a 1:1 ratio to one of two trial groups. Both groups participated in two regimens: a placebo 
vaginal ring regimen and an observational safety regimen (with no placebo vaginal ring). 
Each regimen had 12-week duration. Eighty-two percent (82%) of women in this trial 
reported no ring removals at all for the entire duration of the trial, across trial groups and 
visits, and 99% of participants reported wearing the ring for at least 80% of the days they 
were meant to. Eighteen percent (18%) of women self-reported at least one ring removal 
or expulsion during the course of trial participation. This proportion increased to 22% when 
pharmacy records were incorporated. Many of the reported expulsions and removals were 
related to menses, e.g. heavy blood flow or concern about the ring becoming dirty or 
retaining odour, leading to removal. Ninety-five percent (95%) of women found the ring to 
be very comfortable. All questionnaire responders were willing to use the vaginal ring if 
shown to be effective for HIV prevention15. 
IPM 015 was a Phase I/II randomized, double-blind, placebo-controlled trial conducted at 
10 research centres in Kenya, Malawi, Tanzania and South Africa. The trial was performed 
in 280 HIV-negative, sexually active women, 18 to 40 years of age, to assess and compare 
the safety of 28-day use of Dapivirine Vaginal Ring-004, and a placebo vaginal ring, 
containing no dapivirine. Eligible women were randomly assigned in a 1:1 ratio to the 
dapivirine ring or placebo ring, inserted once every 28 days over a 12-week period. In 
IPM 015, “perfect adherence” was reported by 92% of the female participants. Perfect 
adherence was defined as never having the ring out for more than an entire day. The most 
frequent activity associated with ring expulsion was urination/defecation and the most 
common reason reported by participants for removing the ring themselves was cleaning. 
At the end of the trial, 96% of participants reported that the ring was usually comfortable 
to wear, and 97% reported that they would be willing to use it in the future if it were proven 
effective and they thought they were at risk for HIV infection. Just over 60% of the 
participants in both arms reported that their male partners did not feel the ring at Visit 5 
(trial week 12). A further 22% reported that their partner felt the ring during sex, but that it 


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was not a problem. Only a small number (3%) at Visit 3 (trial week 4) and (1%) at Visit 5 
(trial week 12) reported that her male partner felt the ring and it might be, or definitely was 
a problem for her to continue ring use16. 
1.4.4. Condom Compatibility 
Two clinical condom functionality studies (one with male condoms [IPM 029] and one with 
female condoms [IPM 033]) were conducted with a placebo vaginal ring (silicone 
elastomer ring containing no active ingredient). Results from both studies showed that the 
difference between the total clinical failure rate between condom use with the vaginal ring 
and condom use without the vaginal ring was less than the pre-defined non-inferiority 
margins (3% for the male condom study and 8% for the female condom study). Condom 
use was safe and well tolerated with vaginal ring use. 
Studies with dapivirine-containing vaginal gel formulations (0.05%, 2.5 g) were conducted 
on the following types of male and female condoms: 
•
Non-lubricated latex condoms (male condom)
•
Silicone lubricated latex condoms (male and female condoms)
•
Aqueous lubricated latex condoms (male condom)
•
Polyurethane condoms with silicone lubricant (male and female condoms)
•
Nitrile condoms with silicone lubricant (female condom)
All types of condoms met the acceptance criteria established in the protocol for the mean 
values of the treated samples after treatment with dapivirine gels. The results of condom 
compatibility testing indicate that dapivirine-containing vaginal gel formulations (0.05%, 
2.5 g) have no deleterious effects on the integrity of male or female condoms14. 
1.5. 
Rationale for Protocol IPM 032 
The potential of dapivirine as a safe and efficacious microbicide for prevention of sexual 
transmission of HIV-1 has been evaluated in nonclinical studies (virology studies, 
secondary/safety pharmacology, pharmacokinetics, toxicology) using different in vitro, ex 
vivo and in vivo models, as well as Phase I-II and III clinical trials. Results were 
communicated to the relevant local and international regulatory authorities, IRBs/IECs, 
community representatives, participants and key stakeholders, as appropriate, before 
activation of IPM 032. IPM is pursuing regulatory approval for the product.  
IPM 032, a Phase IIIb follow-on trial to IPM 027, has been designed as an open-label 
clinical trial with the Dapivirine Vaginal Ring (25 mg) to collect additional safety data and 
assess adherence to ring use in healthy, HIV-negative women with monthly (at least one 
to a maximum of three months) followed by 3-monthly research centre follow-up visits over 
12 months. Further, IPM 032 will examine incidence of HIV-1 seroconversion and monitor 
HIV-1 resistance in women who acquire HIV-1 infection. The assessment of the monthly 
visits (first one to three months) followed by 3-monthly research centre follow-up visits will 
provide insight into the feasibility of a 3-monthly scheduling strategy that would be less 
costly and time-consuming in a resource-limited environment such as sub-Saharan Africa. 


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IPM 032 will collect behavioral data needed to support the potential introduction of a 
microbicide as the dapivirine vaginal ring as a public health intervention and to assist with 
future program development. 
2. Trial Objectives
2.1. 
Trial Objectives 
The primary trial objectives are: 
1. To assess the safety profile of the 25 mg Dapivirine Vaginal Ring-004, when 
inserted at monthly intervals, in an open-label trial
2. To assess adherence to the use of the 25 mg Dapivirine Vaginal Ring-004 inserted 
at monthly intervals, in an open-label trial
The secondary trial objectives are: 
1. To assess the incidence of HIV-1 seroconversion
2. To assess the frequency of HIV-1 drug resistance in women who acquire HIV-1
infection
The exploratory trial objectives are: 
1. To assess the feasibility of 3-monthly follow-up visits, as a possible schedule for
post-licensure vaginal ring clinical follow-up
2. To explore the correlation between drug amount and results from the visual
inspection of the returned vaginal rings by research staff between the monthly and
3-monthly research centre follow-up schedules
3. To determine the proportion of participants electing to undergo HIV rapid tests at
the research centres between scheduled 3-monthly visits
4. To explore self-reported acceptability of and adherence to the 25 mg Dapivirine
Vaginal Ring-004.
2.2. 
Trial Endpoints and Assessments 
The primary endpoints are: 
1. Safety
•
All Adverse Events (AEs) assessed by the investigator to be related to the
Dapivirine Vaginal Ring-004
•
All Grade 3 and 4 AEs
•
All Serious Adverse Events (SAEs)
2. Adherence
•
Residual amounts of dapivirine in returned rings; and/or dapivirine
concentrations in plasma and/or dapivirine concentrations in vaginal fluid


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The primary endpoints will be assessed through: 
1. Safety
•
All product-related AEs, Grade 3 or 4 AEs, SAEs, physical examination,
gynaecological 
assessments, including 
pelvic/speculum 
examination,
laboratory tests and other indicated investigations
2. Adherence
•
Determined dapivirine residual amounts in returned used vaginal rings and/or
•
Measured concentrations of dapivirine in plasma and/or
•
Measured concentrations of dapivirine in vaginal fluids
The secondary endpoints are: 
•
The HIV-1 seroconversion rate per 100 woman-years of product use at the end
of the vaginal ring use period
•
HIV-1 drug resistance mutations among participants who acquire HIV-1
infection
The secondary endpoints will be assessed through: 
•
Rapid and specialised laboratory testing according to a pre-specified HIV
testing algorithm
•
Viral genotype (including next generation sequencing [NGS]) and phenotype
resistance testing methods which include sensitive methods to detect low
frequency drug-resistant variants
The exploratory endpoints are: 
•
Feasibility of 3-monthly clinical follow-up schedule
•
Dapivirine residual amounts in returned used vaginal rings and/or dapivirine
concentrations in blood and/or vaginal fluid in correlation with results from the
visual inspection of the returned used vaginal rings by research staff
•
Proportion of participants opting for HIV rapid tests at the research centre 
between scheduled 3-monthly research centre follow-up visits
•
The proportion of women who report the use of the vaginal ring as acceptable
•
Participant self-reported patterns of ring use
The exploratory endpoints will be assessed through: 
•
Participant report of feasibility regarding a 3-monthly clinical follow-up schedule 
(Participant Questionnaire)
•
Number of women opting not to receive two additional rings at the 3-monthly
visits
•
Proportion of returned rings (used and unused) during the 3-monthly clinical 
follow-up schedule
•
Dapivirine residual amounts in returned used vaginal rings and/or dapivirine


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concentrations in blood and/or vaginal fluid 
•
Visual inspection of the returned used vaginal rings by research centre staff
•
Number of participants undergoing HIV rapid tests at the research centres
between scheduled 3-monthly research centre follow-up visits
•
Qualitative data regarding reasons for ring acceptability and self-reported
patterns of ring use
3. Overall Trial Design
3.1. 
Trial Design 
IPM 032 is a Phase IIIb, multi-centre follow-on open-label trial to evaluate the continued 
adherence to and safety of the Dapivirine Vaginal Ring-004, inserted at monthly intervals 
in healthy, HIV-negative women who have participated in the IPM 027 Phase III Dapivirine 
Vaginal Ring-004 trial. All women who have participated in IPM 027 and are HIV-negative 
at screening for IPM 032 will be eligible. An estimate of up to 1400 participants will be 
enrolled. 
All participants will receive the dapivirine vaginal ring containing 25 mg dapivirine 
(Ring-004) at enrolment and will attend a research centre follow-up visit one month after 
enrolment. Following this visit, at investigator’s discretion, a participant can continue on a 
3-monthly visit schedule. Monthly visits may however be extended up to the first three
months of participation. Once the 3-monthly trial visit schedule commences, three rings
will be dispensed. One ring will be self-inserted at the research centre and two additional
rings will be dispensed for the participant to take home, or dispensing will take place as
arranged with the participant.
3.2. 
Trial Duration 
Each participant will engage in the screening process for up to 45 days prior to enrolment 
and will use the Dapivirine Vaginal Ring-004 for a period of up to 12 months. IPM will have 
the option to extend this trial period. Accrual will take place over approximately 6 months 
and those participants who are enrolled more than 6 months after the onset of the trial 
site’s accrual period may have a shortened follow-up period. 
Each participant will have an exit visit approximately 1-2 months after ring discontinuation, 
to assess safety and identify HIV seroconversions after product discontinuation.  
3.3. 
Trial Population 
Up to 1400 HIV-negative women who have participated in the IPM 027 Phase III Dapivirine 
Vaginal Ring-004 trial, who understand the trial and can provide informed consent are 
expected to enrol in this open-label trial. 


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3.3.1. Inclusion Criteria – Women who Previously Enrolled in IPM 027 
Women must meet all the following criteria to be eligible to enrol in the trial: 
1. Previously enrolled in the IPM 027 trial
2. Available for all visits and consent to follow all procedures scheduled for the trial
3. Using an effective method of contraception at the Enrolment Visit, and intending to
use an effective contraceptive method for the duration of trial participation, unless
postmenopausal with no history of menses for one year prior to screening
4. HIV-negative as determined by the HIV algorithm applied at Screening/Pre-
Enrolment
5. Willing to refrain from participation in another research trial using drugs, vaccines,
medical devices and microbicides for the duration of the IPM 032 trial
6. Willing to provide adequate locator information for trial retention purposes and be
reachable per local standard procedures (e.g., by home visit or telephone; or via
family or close neighbour contacts); confidentiality to be maintained
3.3.2. Exclusion Criteria – Women who Previously Enrolled in IPM 027 
Women who meet any of the following criteria are NOT eligible to enrol in the trial: 
1. Investigational product use permanently discontinued in response to an AE (where 
the AE was considered related to investigational product) or safety-related concern
while taking part in the IPM 027 trial
2. Currently pregnant, intends to become pregnant or currently breast-feeding
3. Known drug abuse or alcohol dependence in the 12 months prior to screening
4. Participated in another research trial (other than IPM 027) using drugs, medical 
devices, microbicides or oral pre-exposure prophylaxis agents within 30 days prior
to screening
5. Any new illness or condition(s), chronic condition(s) or abnormal laboratory
finding(s) that, in the opinion of the investigator, might put the participant at risk, or
interfere with the trial objectives or the participant’s adherence to trial requirements
4. Trial Visits and Procedures
4.1. 
Screening Visit
NOTE: For potential participants who do not meet the eligibility criteria, screening 
procedures will be discontinued once ineligibility has been determined. Women who fail 
screening may be re-screened once and may be enrolled if they are found to meet ALL 
inclusion and NO exclusion criteria at the second screening visit.  
In the event that the IPM 027 trial is stopped prematurely and IPM 032 is activated at the 
research centre, the IPM 027 LPUV and the IPM 032 Screening and Enrolment Visits may 
be combined for participants who are eligible to enrol in the IPM 032 trial. In these 


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situations, a separate Screening visit will not be required, and only the procedures 
indicated in italics are required. 
a. Explain the screening, enrolment and trial procedures to the potential participant.
b. If the potential participant agrees, obtain written informed consent. Illiterate
participants may provide a thumbprint or mark witnessed and signed by a person 
independent from trial staff (refer to Section 5.1). A comprehension assessment
checklist will be used to support the consent process (refer to Section 5.2).
c. Assign a unique SCR-ID number to the potential participant (refer to section 5.18).
d. Conduct a review of inclusion/exclusion criteria with the potential participant.
e. Collect demographic information from the potential participant.
f.
Obtain and record locator information.
g. Record basic menses information, relevant medical history, and concomitant
medication taken within the last 30 days (refer to Section 5.7 for more details about
relevant medical history).
h. Perform urine pregnancy testing. Refer pregnant women to local prenatal clinic for
support services (refer to Section 5.6).
i.
Provide HIV/STI risk-reduction counselling (including provision of male and/or
female condoms, should participants wish to receive them), contraceptive
counselling and the provision of contraceptives, if necessary (refer to
Sections 5.3.2 and 5.5).
j.
Provide HIV pre- and post-test counselling (refer to Section 5.3.1).
k.
Perform HIV rapid testing as detailed in Section 5.4.1.
l.
Collect a blood specimen by venepuncture for storage for possible HIV viral 
genotype (including NGS) and phenotype resistance testing , and HIV-1 RNA PCR
testing (Blood volume specified in Appendix C).
m. Perform general physical examination (refer to Section 5.8 for a description of the
elements required in the general physical examination).
n. Perform a pelvic examination (refer to Section 5.9). If the pelvic examination
indicates abnormal findings, e.g., any symptoms or evidence of genital infections, 
abrasions, ulcerations, etc., provide or refer for appropriate treatment.
NOTE: If the participant is menstruating at this visit, the pelvic examination may be
conducted as per investigator and participant discretion. If this is not possible, the
participant will be asked to return 2 days after completion of menstruation.
o. Collect cervicovaginal swabs for STI testing and a specimen for cervical cytology,
if no result is evident within the previous year, or abnormal at last cervical cytology
(refer to Sections 5.11.1 and 5.12). Women with Grade 3 cervical cytology findings
or Grade 3 intraepithelial neoplasia by biopsy (histology result) at screening should
be referred according to National guidelines.
p. Provide treatment and/or referral for STIs and other findings, as necessary (refer
to Section 5.11.2).
q. Perform a urine dipstick analysis (microscopy only if clinically indicated). Collect 
blood samples by venepuncture for syphilis testing (RPR) and confirmatory test (if
required), and the following safety laboratory tests (Blood volumes specified in
Appendix C): haematology (FBC with differential and platelet count), and chemistry


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(creatinine, ALT, AST) (refer to Section 5.10). 
r.
Other procedures, as clinically indicated and with prior approval from IPM.
s. Schedule the Enrolment Visit within 45 days.
4.2. 
Enrolment Visit 
Note: The Enrolment Visit will occur within 45 days after the Screening Visit. 
In the event that the IPM 027 trial is stopped prematurely and the IPM 032 is activated at 
the research centre, the IPM 027 LPUV and the IPM 032 Screening and Enrolment Visits 
may be combined for participants who are eligible to enrol in IPM 032. Trial procedures 
conducted as part of the IPM 027 LPUV will not be repeated for the IPM 032 trial. Only the 
procedures indicated in italics are required. 
Pre-enrolment: 
a. Update locator, menses and pre-enrolment medical history information as
necessary (refer to Section 5.7).
b. Provide contraceptive counselling and contraceptives, if necessary (refer to
Section 5.5).
c. Provide HIV/STI risk reduction counselling, including provision of male and/or
female condoms if the participant wishes to receive them (refer to Section 5.3.2).
d. Record possible social harms (refer to Section 10.2).
e. Obtain and record any concomitant medication information since the last visit.
f.
Perform urine pregnancy testing. Refer pregnant women to local prenatal clinic for
support services (refer to Section 5.6).
g. Provide HIV pre- and post-test counselling (refer to Section 5.3.1).
h. Perform HIV rapid testing as detailed in Section 5.4.2.
NOTE: Additional procedures for participants who test HIV-positive are also 
described in Section 5.4.2 of the protocol.
i.
Reassess and confirm eligibility.
Post-enrolment: 
j.
Assign a unique PID number to the participant (refer to Section 5.18).
k.
Collect a blood specimen by venepuncture for storage for possible HIV viral
genotype resistance (including NGS) and phenotype resistance testing, and HIV-
1 RNA PCR testing (Blood volume specified in Appendix C).
l.
Obtain and record any AE information.
m. Provide adherence counselling, including adherence to trial visit schedule and
requirements and vaginal ring adherence (refer to Section 5.15). Participants will
be instructed to keep the ring inserted for a period of one month. Adherence 
counselling will include information on actions that should be taken in the event of
expulsion or removal of the ring. If the ring comes out or is removed during this
period, the participant should wash her hands, rinse the ring thoroughly in clean 
water and re-insert it.


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n. Provide and explain the use of the diary card to the participant (refer to
Section 5.19).
o. Dispense one vaginal ring to each participant and provide vaginal ring use and
storage instructions (refer to Sections 5.13 and 6.4).
p. Instruct the participant to insert the vaginal ring (refer to Section 5.14).
q. The following procedures are not required, but may be conducted if clinically
indicated: physical and pelvic examination, cervicovaginal sample collection for
STI testing, provision of treatment and/or referral for STIs and other findings,
laboratory testing for safety assessments, urine dipstick analysis (microscopy only 
if clinically indicated) and cervical sample collection for cytology (if no result is
evident within the previous year, or abnormal at last cervical cytology).
r.
Schedule the next visit.
4.3. 
Trial Visits (Monthly research centre visits for the first one to three 
months, and 3-monthly research centre visits thereafter) 
Note: All visit dates will be calculated from the enrolment visit as baseline date. Each 
scheduled visit while the participant is on the IP has a window period of ± 7 days. 
a. Update locator and menses information as necessary.
b. Obtain and record any AE and concomitant medication information since the last 
visit.
c. Record possible social harms (refer to Section 10.2).
d. Perform urine pregnancy test. Refer pregnant women to local prenatal clinic for
support services (refer to Section 5.6).
e. Provide HIV pre- and post-test counselling (refer to Section 5.3.1).
f.
Perform HIV rapid testing as detailed in Section 5.4.3.
NOTE: Additional procedures for participants who test HIV-positive are also 
described in Section 5.4.3 of the protocol.
g. Collect a blood specimen by venepuncture for storage for possible HIV viral
genotype (including NGS) and phenotype resistance testing, and HIV-1 RNA PCR
testing (Blood volume specified in Appendix C). HIV-1 RNA PCR will be performed 
on samples stored at last product use visit and on the last samples collected for 
participants who discontinue from the trial without an exit visit. Only samples from
participants who consented for analysis will be selected for the additional HIV-1
RNA PCR analysis and additional HIV viral genotype (including NGS) and
phenotype resistance testing as needed.
h. Collect blood (Blood volume specified in Appendix C) and vaginal fluid samples
(refer to Section 5.18) for possible measurement of dapivirine concentrations.
NOTE: For dapivirine concentration measurements, blood and vaginal fluid
samples should preferably be collected prior to removal of the vaginal ring.
i.
Instruct the participant to remove the vaginal ring. Collect all used rings from
participants. Perform IP accountability and visual inspection of the returned ring(s). 
Returned rings may be analysed for residual amounts of dapivirine and will be
stored until shipment to the analytical laboratory.


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Dispense one vaginal ring to participants during monthly visits and three vaginal 
rings during 3-monthly visits (or dispense as arranged with the participant) and 
provide vaginal ring use and storage instructions (refer to Sections 5.13 and 6.4).  
j.
Instruct the participant to insert the vaginal ring during monthly visits. Once the
3-monthly trial visit schedule commences, one ring will be inserted at the research
centre and two additional rings will be dispensed for the participant to take home 
(or dispense as arranged with the participant (refer to Section 5.14).
k.
Collect and review the diary card(s) and provide a new diary card(s) if applicable
(refer to Section 5.19).
l.
Administer the Participant Questionnaire at every trial visit (refer to Section 5.16.1).
m. Provide adherence counselling, including adherence to trial visit schedule and
requirements, and vaginal ring adherence (refer to Section 5.15). Participants will
be instructed to keep the ring inserted for a period of one month. Adherence
counselling will include information on actions that should be taken in the event of
expulsion or removal. If the ring comes out or is removed during this period, the
participant should wash her hands, rinse the ring thoroughly in clean water and re-
insert it.
n. Provide contraceptive counselling and contraceptives, if necessary (refer to
Section 5.5).
o. Provide HIV/STI risk reduction counselling; including provision of male and/or
female condoms if the participant wishes to receive them (refer to Section 5.3.2).
p. The following procedures are not required, but may be conducted if clinically
indicated: physical and pelvic examination, cervicovaginal sample collection for
STI testing, provision of treatment and/or referral for STIs and other findings,
laboratory testing for safety assessments, urine dipstick analysis (microscopy only 
if clinically indicated) and cervical sample collection for cytology (if no result is
evident within the previous year, or abnormal at last cervical cytology).
q. Schedule the next visit.
4.4. 
Last Product Use Visit (LPUV) or Early Discontinuation Visit 
Note: LPUVs will be calculated from the enrolment visit as baseline date. This scheduled 
visit has a window period of ± 7 days. 
a. Update locator and menses information as necessary.
b. Obtain and record any AE and concomitant medication information since the last 
visit.
c. Perform a pelvic examination (refer to Section 5.9). If the pelvic examination
indicates abnormal findings, e.g., any symptoms or evidence of genital infections, 
abrasions, ulcerations, etc., provide the participant with or refer the participant for 
appropriate treatment.
NOTE: If the participant is menstruating at this visit, the pelvic examination may be
conducted as per investigator and participant discretion. If this is not possible, the
participant will be asked to return 2 days after completion of menstruation.
d. Record possible social harms (refer to Section 10.2).
e. Perform a general physical examination (refer to Section 5.8 for a description of


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the elements required in the general physical examination). 
f.
Instruct the participant to remove the vaginal ring. Perform IP accountability and
visual inspection of the returned ring(s). Returned rings may be analysed for 
residual amounts of dapivirine and will be stored until shipment to the analytical
laboratory.
g. Collect and review the diary card(s).
h. Administer the Participant Questionnaire (refer to Section 5.16.1).
i.
Provide HIV/STI risk reduction counselling; including provision of male and/or
female condoms if the participant wishes to receive them (refer to Section 5.3.2).
j.
Perform contraceptive counselling and provide contraceptives, if necessary (refer
to Section 5.5).
k.
Perform urine pregnancy test. Refer pregnant women to local prenatal clinic for
support services (refer to Section 5.6).
l.
Collect cervicovaginal swabs for STI testing (refer to Sections 5.11.1).
m. Provide STI treatment if needed (refer to Section 5.11.2).
n. Provide HIV pre- and post-test counselling (refer to Section 5.3.1).
o. Perform HIV rapid testing as detailed in Section 5.4.3.
p. Collect a blood specimen by venepuncture for storage for possible HIV viral
genotype (including NGS) and phenotype resistance testing , and HIV-1 RNA PCR
testing (Blood volume specified in Appendix C). HIV-1 RNA PCR will be performed 
on samples stored at last product use visit and on the last samples collected for
participants who discontinue from the trial without an exit visit. Only samples from
participants who consented for analysis will be selected for the additional HIV-1
RNA PCR analysis and additional HIV viral genotype (including NGS) and
phenotype resistance testing as needed.
q. Collect blood (Blood volume specified in Appendix C) and vaginal fluid samples
(refer to Section 5.17) for possible measurement of dapivirine concentrations.
NOTE: For dapivirine concentration measurements, blood and vaginal fluid
samples should preferably be collected prior to removal of the vaginal ring.
r.
The following procedures are not required but may be conducted if clinically
indicated: laboratory testing for safety assessments, urine dipstick analysis
(microscopy only if clinically indicated) and cervical sample collection for cytology
(if no result is evident within the previous year, or abnormal at last cervical 
cytology).
s. Schedule the exit visit.
4.5. 
Exit Visit 
Note: Exit Visits will occur approximately 1-2 months after ring discontinuation. If the 
outcome of confirmatory tests is pending, the exit visit may be conducted more than 
2 months after the last product use visit, but should be performed as soon as possible 
after the results are available. Participants will be notified of any abnormal laboratory 
findings, and return to the research centre prior to the exit visit as needed for treatment 


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and/or referral. Additional trial procedures for exit visits scheduled following HIV 
seroconversion are described in Section 5.4.4. 
a. Obtain and record any AE and concomitant medication information since the last 
visit.
b. Record possible social harms (refer to Section 10.2).
c. Perform contraceptive counselling and provide contraceptives, if necessary (refer
to Section 5.5).
d. Provide HIV/STI risk reduction counselling; including provision of male and/or
female condoms if the participant wishes to receive them (refer to Section 5.3.2).
e. Provide HIV pre- and post-test counselling (refer to Section 5.3.1).
f.
Perform HIV rapid testing as detailed in Section 5.4.4 (additional procedures for
participants who test HIV-positive are also described in Section 5.4.4 of the
protocol).
g. Collect a blood specimen by venepuncture for storage for possible HIV viral
genotype (including NGS) and phenotype resistance , and HIV-1 RNA PCR testing
(Blood volume specified in Appendix C). HIV-1 RNA PCR will be performed on
samples stored at last product use visit and on the last samples collected for
participants who discontinue from the trial without an exit visit. Only samples from
participants who consented for analysis will be selected for the additional HIV-1
RNA PCR analysis and additional HIV viral genotype (including NGS) and
phenotype resistance testing as needed.
h. Provide final safety and STI laboratory test results to participant.
i.
The following procedures are not required, but may be conducted if clinically
indicated: physical and pelvic examination, cervicovaginal sample collection for
STI testing, provision of treatment and/or referral for STIs and other findings,
laboratory testing for safety assessments, urine dipstick analysis (microscopy only 
if clinically indicated) and cervical sample collection for cytology (if no result is
evident within the previous year, or abnormal at last cervical cytology).
j.
Exit the participant from the trial.
4.6. 
Unscheduled Visits 
Unscheduled visits may be performed at any time during the trial for HIV, STI or pregnancy 
testing, collection of rings or if the participant is experiencing any problems, e.g., vaginal 
complaints, difficulties with re-inserting the ring in cases of accidental expulsion or ring 
removal, or accidental loss of the ring or product adherence challenges. Participants will 
also be notified of any abnormal laboratory findings, and return to the research centre prior 
to the next scheduled visit as needed for treatment and/or referral to an outside medical 
facility. Additional laboratory testing to evaluate AEs that are suspected to be associated 
with use of the IP may be performed where indicated, in consultation with the IPM Clinical 
Physician. 
All unscheduled visits will be documented in the source documents and applicable case 
report forms (CRFs). 


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4.7. 
Missed and Late Visits 
Trial staff will make every effort to contact participants to return to the research centre for 
scheduled visits. If a participant does not return to the research centre for a scheduled 
visit during the trial window, e.g., within ± 7 days of a scheduled visit, continued attempts 
to contact the participant will be made as per local standard operating procedure (SOP) 
and documented in the source documents. 
If the participant does not return to the research centre for a scheduled visit prior to the 
start of the trial window of the next visit, the visit will be considered missed. For example, 
if a participant does not return for Visit 2 by the time the trial window has begun for Visit 
3, i.e., within 7 days from Visit 3, Visit 2 will be considered missed. Trial procedures will 
be performed as scheduled for the current visit (e.g. Visit 3 in this instance) or as deemed 
necessary by the investigator or IPM Clinical Physician (or designee). Missed visits will be 
documented as protocol deviations. Trial staff should ensure that all used or unused 
vaginal rings that were to be returned at the missed visit are retrieved as soon as possible. 
In the event that a participant will be away and unable to attend one of the Trial Visits 
where new vaginal rings would be dispensed, the investigator or designee could dispense 
additional ring(s) on a case-by-case basis. Research centre staff will enquire about 
adverse events and concomitant medication over the telephone; and other information will 
be collected as applicable.  
If a participant presents for a visit outside the window for a scheduled trial visit but prior to 
the start of the window for the next visit, it will be treated as a late visit and documented 
as a protocol deviation. All trial procedures scheduled for the late scheduled visit will still 
be performed. The participant will then resume her original visit schedule. 
If a LPUV is missed, STI testing should be performed at the Exit Visit. 
4.8. 
Protocol Deviations 
A protocol deviation is defined as any change, non-compliance or divergence from the 
approved protocol. The non-compliance may be either on the part of the participant, the 
investigator, the research centre staff or laboratory staff. It is the responsibility of the 
research centre to identify and report protocol deviations according to the guidelines of 
the sponsor and the local IRB/IEC. The research centre must report protocol deviations to 
IPM using designated forms. The principal investigator and research centre staff are 
responsible for being familiar with and adhering to their IRB/IEC requirements. In response 
to noted protocol deviations, research centre personnel are to promptly implement 
corrective actions. 
4.9. 
Early Discontinuation Visits 
Participants may be discontinued early from the trial prior to completion of the last trial visit 
for any of the following reasons: 
•
Participant withdraws her consent.
•
Participant is lost to follow-up, i.e., research centre is unsuccessful (following


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reasonable attempts as defined in the research centre SOP) in contacting 
participant or bringing the participant back to the research centre. 
•
Participant tests HIV-positive according to the HIV-testing algorithm in
Appendix B.
•
If, for safety reasons, the investigator considers it in the best interest of the
participant to discontinue her from the trial.
•
At the discretion of the investigator, Sponsor, IRB/IEC or the government
health authority.
The date and reason for permanent trial discontinuation will be noted in the source 
documents and applicable CRFs. All participants who are prematurely discontinued from 
the trial will be encouraged to return to the research centre for a final evaluation, at which 
time all trial procedures scheduled for the last product use visit will be performed. An 
optional exit visit approximately 1-2 months after product discontinuation can be 
completed. For participants who discontinue from the trial without an exit visit, a HIV-1 
RNA PCR will be performed on available samples. 
Participants who are considered lost to follow-up will be temporarily discontinued from the 
trial. Reasonable contact attempts will be made according to the locator information 
provided by the participant and local SOPs, and temporarily early trial termination will be 
documented in the source documents and applicable CRFs. If a participant already 
considered lost to follow-up returns to the research centre prior to the centre’s trial 
completion, the participant’s file (including CRFs) may be re-opened to perform trial 
discontinuation procedures. The participant may be considered for continuation on the trial 
at the discretion of the principal investigator in consultation with the IPM Clinical Project 
Manager, depending on the reason for the missed visits. A final trial termination will be 
documented in the source documents and applicable CRFs during the trial closure for all 
temporarily early trial terminations. 
4.10. 
Premature Discontinuation of the Trial 
IPM has the right to terminate this trial at any time for any reason. If the trial is prematurely 
terminated, the investigator must promptly inform the participants and the IRBs/IECs, and 
ensure proper medical follow-up of participants in consultation with IPM. If the trial is 
prematurely terminated, all procedures and requirements pertaining to the archiving of the 
trial documents will be observed. IPM will provide the research centres with instructions 
on the proper disposition of any clinical supplies at the centre.  
5. Trial Procedure Details
5.1. 
Informed Consent 
The informed consent documents will include all the information about the trial required by 
GCP and will make provision for the dated signatures of the participant, the principal 
investigator or designated trial staff conducting the informed consent process, and when 
required, also for a dated signature by an impartial witness. The informed consent process 
will be administered at the Screening Visit. 
The informed consent process will include adequate time for each potential participant to 


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have any trial related questions answered by appropriately qualified and trained trial staff 
as designated by the investigator, and the entire process will be documented in the source 
documents. 
At screening, potential participants who agree to participate in the trial will sign and date 
the ICF. The ICF will also be signed and dated by the trial staff administering the consent 
process as delegated by the principal investigator according to the research centre SOP. 
If a potential participant is functionally illiterate, the informed consent document(s) and any 
written trial-related materials must be read to her in the language best understood by the 
potential participant in the presence of an impartial literate witness. After the illiterate 
participant has orally consented to participate in the trial, and, if capable of doing so, has 
signed the ICF or provided a thumbprint or mark that was witnessed by the impartial 
witness, this impartial witness must sign and personally date the ICF. By signing the ICF 
the impartial witness attests that the information in the participant information sheet and 
any other written information was explained to, and apparently understood by, the 
participant or the participant’s legally acceptable representative and that informed consent 
was freely given by the participant or the participant’s legally acceptable representative. 
The signed and dated ICFs will be retained at the research centre. A copy of the signed 
and dated ICFs will be offered to the participant. If the participant is not willing to receive 
the documents, the second copy will be retained at the research centre. Likewise, during 
the trial, signed and dated ICF updates and any amendments to written trial-related 
materials to be given to participants will be offered to the participant but retained at the 
research centre if the participant is unwilling to receive the documents. Documentation of 
the participant’s refusal to accept a copy of the ICF(s) or other trial-related materials will 
be noted in the source documents.  
The consent documents and any trial-related materials given to the participant will be 
translated and back-translated in the local languages according to local IRB/IEC 
requirements and regulatory authority guidelines. Information in the informed consent 
documents and trial-related material will be verbally communicated by trial staff, in the 
language preferred by the participant, and copies of the documents and trial-related 
materials will be offered to her in her preferred language. Documentation will be required 
to verify who performed translation/back-translation of the materials as well as a written 
statement by the translator indicating that the consent form(s) is an accurate translation of 
the accompanying English version. This is the principal investigator’s responsibility. 
All research centre-specific informed consent documents will first be reviewed and 
approved by IPM and then approved by the responsible IRB and/or local IEC prior to 
administration to the participants. 
If new information becomes available which may be relevant to the participant’s 
willingness to continue trial participation, the information will be provided via IRB and/or 
IEC-approved revised informed consent documents or addenda to the original informed 
consent documents in a timely manner and will be signed and dated by the participant in 
the same manner described above. 
Written informed consent will be obtained from all participants selected for participation in 
the in-depth individual interviews (IDIs). Written informed consent will also be obtained for: 
HIV-1 RNA PCR, viral genotype (including NGS) and phenotype resistance testing on the 
stored samples of the last product use visit and on the last samples collected for 


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participants who discontinue from the trial without an exit visit, longer term storage and 
shipping out of the country, if needed. 
5.2. 
Comprehension Assessment Checklist 
Trial staff will assess the potential participant’s understanding of informed consent 
information prior to obtaining a signature on the ICF at the Screening Visit. This 
assessment will be done using a standardised comprehension assessment checklist. All 
comprehension problems that are discovered during the assessment will be discussed 
until staff member(s) are satisfied that the participant can verbalise her understanding of 
the issue. This process will be documented on the comprehension assessment checklist. 
This checklist will be recorded in source documentation at the research centre. A 
participant who cannot demonstrate comprehension of the informed consent information 
will not be enrolled in the trial.  
5.3. 
HIV Counselling 
5.3.1. HIV Pre- and Post-test Counselling 
At all visits where HIV testing is performed, pre- and post-test counselling will be provided 
according to the National Guidelines for HIV Counselling and Testing. Adaptations of 
these guidelines in accordance with locally accepted standards of practice are allowed. 
Each research centre will document the counselling policies and procedures prior to trial 
implementation for purposes of staff training, quality assurance, and trial monitoring. 
A comprehensive package of post-test counselling and psychosocial support will be 
provided to women who test HIV reactive at any point during trial participation. Initial 
counselling services will be provided at the research centre and women will be referred 
for additional counselling, support services and treatment. These services will be identified 
by the research centres prior to trial initiation and referral procedures will be documented 
in writing by the centre. 
5.3.2. HIV/STI Risk Reduction Counselling 
HIV/STI risk reduction counselling will be in accordance with local guidelines. Counselling 
will be provided at all research centre visits. Efforts will be made to ensure standardisation 
of risk reduction counselling at the trial research centres. 
NOTE: Risk reduction counselling will include recommendation of male and/or female 
condom use. Participants will be provided with a supply of male non-spermicidal condoms 
and/or female condoms during each trial visit, if they are willing to accept them. The use 
of female condoms is permitted in this trial. 
5.4. 
HIV Testing and Management 
The research centres will inform IPM Medical Safety of any new HIV seroconversions 
within 48 hours of diagnosis. The applicable regulatory authorities and independent ethics 
committees who require expedited notification of HIV seroconversion will be notified by 
either IPM or the research centre in accordance with standard operating procedures and 


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policies of the regulatory authorities or independent ethics committees. The details of the 
HIV rapid test kits will be specified in the Laboratory Manual, as part of the SOM. 
Participants will be tested for HIV using two highly sensitive antibody rapid tests (Test 1 
and Test 2). 
5.4.1. Screening Visit 
If both test results are non-reactive, the participant could potentially be enrolled in the trial 
if she is otherwise eligible.  
If both Test 1 and Test 2 are reactive at screening, the potential participant is considered 
to be HIV seropositive and not eligible for enrolment. Initial counselling services will be 
provided at the research centre and the participant will be referred for additional 
counselling, support services and treatment. These referral systems will be implemented 
by research centres prior to trial start. It is the participant’s responsibility to follow up with 
relevant medical services once referral has been initiated by the research centre. 
If Test 1 and Test 2 yield discordant results, a highly specific HIV antibody Test 3 will be 
performed. If Test 3 is reactive then the potential participant is considered to be 
HIV-seropositive and is not eligible for enrolment. If Test 3 is non-reactive, the person is 
considered to be potentially HIV-seronegative and can be given a date for enrolment into 
the trial. Refer to Appendix B: HIV Testing Algorithms. 
A blood sample will be obtained by venepuncture to be sent for sample storage locally or 
at a central laboratory, for potential HIV-1 RNA PCR, viral genotype (including NGS) and 
phenotype resistance testing if the participant seroconverts (blood volume specified in 
Appendix C). Storage samples for participants who do not enrol will be destroyed 
according to research centre SOPs. 
NOTE: For the purposes of HIV rapid testing at screening, blood may be obtained by finger 
prick or venous sampling. If the national regulatory authority of the country in which the 
research centre is situated requires that a national testing algorithm be used during the 
screening process, this will be performed, in addition to the IPM 032 HIV testing algorithm, 
as part of the screening process and documented as such. 
5.4.2. Enrolment Visit 
On the scheduled day of possible enrolment, the participant will be tested for HIV and will 
only be enrolled if the results are considered to be HIV-seronegative and the participant is 
otherwise eligible.  
Test 1 and Test 2 will be performed. If both test results are non-reactive and there is no 
history to suggest recent exposure that could be masked during the window period, the 
potential participant will be considered HIV-seronegative and eligible for enrolment. A 
blood sample will be obtained by venipuncture to be sent for sample storage locally or at 
a central laboratory, for potential HIV-1 RNA PCR, viral genotype (including NGS) and 
phenotype resistance testing if the participant seroconverts (blood volume specified in 
Appendix C). Storage samples for participants who do not enroll will be destroyed 
according to local SOPs. 
If both Test 1 and Test 2 are reactive, the participant is considered to be HIV seropositive 


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and not eligible for enrolment. Initial counselling services will be provided at the research 
centre and the woman will be referred for additional counselling, support services and 
treatment. 
A rapid Test 3 will be performed for all discordant rapid test results. If Test 3 is reactive 
then the potential participant is considered to be HIV-seropositive and not eligible for 
enrolment. She will be counselled and referred to the local health facilities for appropriate 
follow-up. If Test 3 is non-reactive, the participant is considered to most likely be 
HIV-seronegative, and a sample will be collected for HIV-1 RNA PCR testing and the 
Enrolment Visit should be re-scheduled within the screening window period (split visit). If 
the HIV-1 RNA PCR does not detect HIV RNA copies, the participant can be enrolled. 
Storage samples should be collected on the second day of the split visit. If the HIV-1 RNA 
PCR does detect HIV RNA copies then she is not eligible for enrolment. She will be 
counselled and referred to the local health facilities for appropriate follow-up Refer to 
Appendix B: HIV Testing Algorithms. 
5.4.3. Trial Visits and LPUV 
The HIV rapid and confirmatory laboratory tests used in the HIV-testing algorithm will 
detect both subtypes, HIV-1 and HIV-2. The testing algorithm (refer to Appendix B) will be 
applied for all Trial Visits and LPUV. HIV testing while the participant is enrolled in the trial 
will be performed on blood samples obtained by venipuncture (blood volumes specified in 
Appendix C). 
If both the HIV rapid tests (Test 1 and Test 2) are non-reactive, the participant will be 
considered HIV-seronegative and continue using the IP. If both HIV rapid tests are 
reactive, IP will be withheld until HIV infection has been confirmed. Trial procedures 
relevant to the LPUV will be performed. Additional confirmatory testing will be performed 
by Western Blot and other confirmatory tests, where appropriate. IP may be re-introduced 
after consultation with IPM, if confirmatory test(s) indicate(s) that the participant is not HIV 
infected. The participant must have a negative pregnancy test prior to re-introduction of 
IP. A pelvic examination should be performed according to investigator’s discretion prior 
to re-introduction of IP if clinically indicated. If confirmatory test(s) indicate(s) that the 
participant is HIV infected, the participant will be permanently discontinued from IP and 
the trial. 
If the Test 1 and Test 2 results are discordant, a HIV rapid Test 3 will be performed on the 
same blood sample as used for Test 1 and Test 2. If Test 3 is reactive, IP will be withheld 
until HIV infection has been confirmed. Trial procedures relevant to the LPUV will be 
performed. Additional confirmatory testing will be performed by Western Blot and other 
confirmatory tests, where appropriate. IP may be re-introduced after consultation with IPM, 
if confirmatory test(s) indicate(s) that the participant is not HIV infected. The participant 
must have a negative pregnancy test result prior to re-introduction of IP. A pelvic 
examination should be performed according investigator’s discretion prior to re-
introduction of IP, if clinical indicated. Nucleic acid-amplification testing (NAAT) by a HIV-1 
RNA PCR test will be performed on stored samples in reverse sequential order to estimate 
the time point of HIV infection. The participant will be counselled and referred for 
appropriate counselling and care. 
If Test 3 is non-reactive, the participant is considered to be HIV-seronegative. The 
participants who have discordant HIV test results at Trial Visits will continue on IP and be 


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requested to return for repeat HIV rapid testing after two weeks. In such cases the 
research centre will notify the IPM Clinical Project Manager or designee. Additional 
confirmatory tests may be indicated at any stage in consultation with the IPM Clinical 
Project Manager or designee. If a similar result is obtained on testing after two weeks, a 
sample should be collected for a quantitative HIV-1 PCR test and the research centre will 
notify the IPM Clinical Project Manager and Laboratory Specialist. 
If the HIV-1 RNA PCR result is undetectable: 
•
The participant is considered to not be HIV-infected.
•
The participant should continue in the trial with HIV rapid testing only performed 
at scheduled visits, even if the same pattern of discordant results continues. It
will not be necessary to recall the participant for 2-weekly testing.
•
The research centre will notify the IPM Clinical Project Manager or designee of
the outcome.
If the HIV-1 RNA PCR result is detectable: 
•
The participant is considered HIV-infected and IP should be discontinued
immediately. The research centre will notify the IPM Clinical Project Manager
or designee immediately.
All enrolled participants will in addition, have blood samples collected at each trial visit to 
be stored locally or at a central laboratory, for possible HIV-1 RNA PCR, genotype 
(including NGS) and phenotype resistance testing. If a participant subsequently 
seroconverts (i.e. is confirmed HIV-positive) while on the IP, the stored samples will be 
tested in reverse sequential order until an undetectable PCR test result is obtained. This 
will be conducted to approximate the period of HIV infection. If the enrolment HIV-1 RNA 
PCR test result is positive, the participant is not considered to have been infected while 
using the IP. 
Blood (blood volume as specified in Appendix C) and vaginal fluid samples will also be 
obtained for dapivirine measurement at the point of HIV seroconversion according to the 
HIV testing algorithm described above. Stored samples (blood and vaginal fluids) will be 
analysed retrospectively as described in Section 5.17. 
Any participant who is confirmed HIV-infected while on the trial will be permanently 
discontinued from IP and the trial. An exit visit will be scheduled approximately 1-2 months 
following IP discontinuation. Initial counselling services will be provided at the research 
centre and women will be referred for additional counselling, support services and 
treatment. In addition, these women will be offered the option of enrolling for IPM’s 
seroconverter protocol. 
In an instance where a participant is determined to be HIV-seropositive (as determined by 
HIV rapid tests, Western Blot; and any other confirmatory tests, if applicable), but cannot 
be confirmed as HIV-infected (HIV-1 RNA PCR) the participant will be discontinued from 
IP and the protocol-required procedures as per original trial visit schedule will be 
conducted at the investigator’s discretion. Samples for measurement of dapivirine levels 
will no longer be collected. Additional testing to demonstrate HIV infection may be 
performed. Participants will be followed up until the exit visit according to the original 


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enrolment date. 
5.4.4. Exit Visit 
For participants confirmed as HIV-negative prior to the exit visit 
If both HIV rapid tests (Test 1 and Test 2) are non-reactive, the participant will be 
considered HIV-seronegative. If both Test 1 and Test 2 are reactive, confirmatory testing 
will be performed by Western Blot and other confirmatory tests, where appropriate. 
Samples for possible HIV-1 RNA PCR, genotype (including NGS) and phenotype 
resistance testing will be collected. Once HIV infection has been confirmed, this will be 
considered an HIV seroconversion after product discontinuation and may be a 
combination of both women infected during IP use who seroconverted after IP 
discontinuation, as well as women infected after IP use. Nucleic acid-amplification testing 
(NAAT) by a HIV-1 RNA PCR test will be performed on stored samples in reverse 
sequential order to estimate the time point of HIV infection. 
Initial counselling services will be provided at the research centre and women will be 
referred for additional counselling, support services and treatment. 
A HIV rapid Test 3 will be performed for discordant rapid Test 1 and Test 2 results. If Test 3 
is reactive then the participant will be considered to be HIV-seropositive. Additional 
confirmatory testing will be performed by Western Blot and other confirmatory tests, where 
appropriate. Samples for possible HIV-1 RNA PCR, genotype (including NGS) and 
phenotype resistance testing will be collected. The participant will be counselled and 
referred to local health facilities for social support or other medical services as clinically 
indicated. If Test 3 is non-reactive, the participant is considered to be HIV-seronegative 
and will be counselled appropriately. Refer to Appendix B: HIV Testing Algorithms, and 
Appendix C: Visit Schedule and Blood Volumes. 
For participants confirmed as HIV-infected prior to the exit visit 
As stated in Section 5.4.3 above, an exit visit will be scheduled approximately 1-2 months 
following confirmed HIV-seroconversion and IP discontinuation. Blood samples for HIV-1 
RNA PCR, genotype (including NGS) and phenotype resistance testing will be collected 
from these participants, but no further HIV counselling and testing will be done unless 
indicated for additional confirmatory testing. 
Participants who become infected with HIV during the course of an IPM trial will be referred 
for appropriate HIV-related care and ARV therapy as above. The threshold for initiation of 
ARV treatment will be determined with reference to the WHO treatment guidelines if no 
country specific guidelines are available. Women who become pregnant and HIV positive 
during the trial will be referred for appropriate Prevention of Mother-to-Child Transmission 
of HIV (PMTCT) services. 
The research centres will inform IPM Medical Safety of any new HIV infections within 
48 hours of diagnosis. The applicable regulatory authorities and ethics committees who 
require expedited notification of HIV seroconversion will be notified by either IPM or the 
research centre in accordance with standard operating procedures and policies of the 
regulatory authorities or ethics committees. 


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5.5. 
Contraceptive Counselling and Management of Contraception 
Contraceptive counselling will be provided at all research centre visits. Counselling will be 
tailored per research centre, depending on local community and regional guidelines and 
will be detailed in research centre procedures. Counselling will include information about 
medication side effects and interactions, the importance of contraceptive adherence for 
the duration of the trial; what to do in the event of accidental non-adherence and advice 
on how to remain adherent. 
Participants will also be counselled that if they become pregnant during the trial, they will 
immediately discontinue the IP and be referred to the local prenatal services for support 
and further management of the pregnancy. Refer to Pregnancy Testing and Management 
below in Section 5.6. 
To meet eligibility criteria, unless postmenopausal with no history of menses for one year 
prior to screening, participants must be on an effective method of contraception prior to 
enrolment, have demonstrated adherence to her chosen method of contraception and 
have no significant resultant problems.  
In order to address challenges that participants may experience in consistently obtaining 
an effective method of contraception, research centres will provide participants with 
contraceptives from screening for the duration of the trial, if required. The contraceptives 
provided will be consistent with what is available locally. Alternatively, participants will be 
referred to the local family planning clinic or continue accessing contraception from local 
family planning clinics. Under supervision of the investigator or designated qualified 
personnel, enrolled participants may switch from one contraceptive method to another, if 
effective contraception is maintained. 
5.6. 
Pregnancy Testing and Management 
A urine pregnancy test will be performed at all scheduled trial visits, except for the Exit 
Visit, and can be performed additionally at unscheduled visits if any reason exists to 
suspect pregnancy or, in the event of a participant defaulting on her contraception, prior 
to recommencing contraception. 
If a potential participant tests positive for pregnancy during screening, she is not eligible 
to enrol in the trial, but will receive referrals to prenatal clinics or other appropriate facilities. 
A product hold will be implemented if a woman tests positive for pregnancy while on IP. 
Vaginal ring(s) will be retrieved from the participant, but the participant will not be 
withdrawn from the trial. Protocol-specified visit schedule and procedures will continue 
except for IP-related procedures and other examinations if contra-indicated by pregnancy. 
The participant will be referred to a local prenatal clinic for medical services. The research 
centres will be asked to report all pregnancies to IPM within 48 hours of a positive 
pregnancy test or a confirmatory serum pregnancy test, if indicated. A confirmatory serum 
pregnancy test may be requested at the discretion of the investigator or a designated 
qualified member of the trial staff if reason exists to suspect a false positive urine 
pregnancy test. If the serum pregnancy test is negative, the investigator can consider 
recommencing use of the ring. If the participant indicates a change in pregnancy status or 
the participant’s clinical history indicates a change in her pregnancy status after the 


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product hold (birth or termination), a urine pregnancy test may be performed. A 
confirmatory serum pregnancy test may be requested at the discretion of the investigator 
or a designated qualified member of the trial staff if reason exists to suspect a false positive 
urine pregnancy test. If the urine pregnancy test is negative, the investigator can consider 
recommencing IP. The participant must have a negative urine pregnancy test prior to re-
introduction of IP, and should not be breast-feeding. A pelvic examination should be 
performed prior to re-introduction of IP. 
Women who become pregnant and HIV-positive during the trial will be referred for 
appropriate PMTCT services. 
Should a participant have a positive pregnancy test in an instance where she was 
determined to be HIV-seropositive but could not be confirmed as HIV-infected, was 
discontinued from IP use and consented to continued participation in the trial without IP, 
she will be allowed to continue in the trial to allow for continued follow-up and evaluation 
of her HIV status until the Exit Visit according to the original enrolment date or until she is 
confirmed to be HIV-infected, whichever occurs earlier. 
The research centres will be required to provide quarterly updates on the progress and 
outcome of the pregnancy as well as the first year of life of the child for inclusion in the 
Sponsor maintained pregnancy registry. This requirement may vary, depending on 
country-specific regulations. 
5.7. 
Demographics and Medical History 
At the Screening Visit basic demographic information will be collected. A confidential 
master log of participants, with demographic and locator information will be maintained.  
At both the Screening and Enrolment Visits (pre-enrolment) relevant medical history will 
be obtained, including but not limited to history of STIs, gynaecological conditions, 
hospitalisations, surgery, allergies, any conditions requiring prescription or chronic 
medication, i.e. > 2 weeks in duration, and acute conditions occurring prior to enrolment. 
5.8. 
Physical Examination 
A general physical examination will be conducted at screening and the LPUV, and will 
include weight, vital signs (body temperature, pulse rate, respiration rate, blood pressure), 
and examination of skin, respiratory, cardiovascular, central nervous and abdominal 
systems, as well as an assessment of cervical and axillary lymph nodes. Height will be 
measured only at the Screening Visit. A symptom-directed physical examination will be 
conducted at any visit if clinically indicated. 
5.9. 
Pelvic Examination 
A pelvic examination will be performed at screening and LPUV, or at any visit if clinically 
indicated. On-trial examinations will be performed to assess safety, i.e., any local vaginal 
reactions. 


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If the participant is menstruating on the day of a visit where pelvic examination is due, all 
procedures, including the pelvic examination can be conducted as per investigator and 
participant discretion. If this is not possible, the participant will be asked to return 2 days 
after completion of menstruation, within the window period of the visit. 
Any unexpected or abnormal vaginal bleeding should be investigated to identify the 
possible source. A follow-up pelvic examination should be performed to ensure resolution 
of the condition as indicated. 
5.10. 
Laboratory testing for safety assessments and urine dipstick 
analysis 
Safety laboratory assessments and urine dipstick analysis (microscopy only if clinically 
indicated) will be conducted at the screening visit, or any other trial visit if clinically 
indicated. Blood specimens for laboratory testing (haematology and chemistry testing) will 
be obtained by venepuncture. Haematology will include a full blood count, differential, and 
platelet count. Chemistry tests will include creatinine, AST and ALT. Details of blood 
volumes are specified in Appendix C. At the discretion of the investigator or designee, 
each potential participant may be retested once for safety laboratory tests during the 
screening period. 
Additional tests may be performed at the investigator’s discretion after discussion with the 
IPM Clinical Physician (or designee) based on symptomatology and clinical assessment 
of participants. Additional descriptive information regarding specimen collection and 
processing for all tests will be detailed in the SOM. 
All laboratory results will be reviewed by the investigator or appropriately qualified and 
trained trial staff as designated by the investigator, and documented on the original 
laboratory report itself. 
5.11. 
STI Testing and Management 
5.11.1. STI Testing 
Cervicovaginal samples will be collected for STI testing at screening and the LPUV, or any 
other trial visit if clinical indicated. All participants will be evaluated for Trichomonas 
vaginalis (TV), Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT). At 
screening, blood will be collected by venepuncture for Syphilis (RPR) testing (Blood 
volume specified in Appendix C). TPHA/TPPA testing will be performed if the RPR is 
reactive. 
Additional descriptive information regarding specimen collection to test for STIs and 
processing of all tests will be detailed in the Laboratory Manual, as part of the SOM. 
NOTE: Documentation will be made in applicable CRFs for all cervicovaginal samples 
obtained in the presence of cervicovaginal blood. 
The investigator or appropriately qualified and trained trial staff as designated by the 
investigator will review all results, including rapid and laboratory tests, and the review will 


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be documented by the reviewer on the original laboratory report itself. 
5.11.2. STI Management 
All participants who present with STIs will be managed appropriately as clinically indicated 
at the research centre or referred to a local health facility, according to local STI Treatment 
Guidelines. Cervicovaginal swabs may be collected from these participants, at the 
investigator’s discretion or when required by local standard of care. Etiological 
management may be applicable following STI testing, according to the etiological 
diagnosis. 
The Clinical Management of Genital Diagnoses will be detailed in the SOM for guidelines 
to determine whether the vaginal ring requires temporary or permanent removal and to 
provide guidance regarding follow up recommendations.  
5.12. 
Cervical Cytology 
A cervical cytology sample will be collected at the Screening Visit if not done within the 
previous year, or if the result was abnormal at the last point of testing. Further details will 
be provided in the Laboratory Manual, as part of the SOM. 
Women with abnormal cytology findings will be referred for appropriate medical services 
based on local standard of care for management of abnormal cervical cytology. Research 
centres will implement these referral systems prior to trial start.  
5.13. 
Vaginal Ring Dispensing 
Vaginal rings will be dispensed at the Enrolment Visit and subsequent Trial Visits. In the 
event that a participant will be away and unable to attend one of the Trial Visits where new 
vaginal ring(s) would be dispensed, the investigator or designee could dispense additional 
ring(s) on a case-by-case basis. All such circumstances must be documented fully by the 
investigator as described in the IPM 032 SOM. If a participant requires an additional ring 
at a time other than when they are scheduled to receive one, they will be required to attend 
the research centre for an interim visit. During the monthly trial visit period, the participants 
will be instructed to self-insert the newly-dispensed vaginal ring at the research centre and 
to remove the ring at the next scheduled visit. During the 3-monthly trial visit period, the 
participants should self-insert one ring during the trial visit and each of the two additional 
rings at monthly intervals until their next scheduled research centre visit. Vaginal ring bags 
will be provided to participants during the 3-monthly trial visit period for the storage of the 
used rings, together with instructions on the storage of the unused and used rings. 
During the 3-monthly trial visit period, optional vaginal ring dispensing and return 
arrangement will be made with participants who prefer not to have additional vaginal rings 
in their possession. These participants will be provided with the option to return used 
vaginal rings and to collect new rings at the research centres at time intervals suitable to 
them, provided that the intervals allow for new vaginal rings to be inserted monthly. 
Optional HIV rapid tests will be offered to participants during these interim visits and will 
be conducted according to the Trial Visits HIV algorithm (refer to Appendix B). Participants’ 
preference regarding the intervals for product dispensing and return will be documented 


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in the source document and applicable CRFs. 
5.14. 
Vaginal Ring Insertion and Ring Removal 
At the Enrolment and Trial Visits, participants will insert the vaginal rings under research 
centre supervision, as applicable. The participant will be instructed to thoroughly wash her 
hands, relax, and get into a comfortable position either standing with one foot on a chair, 
lying on her back with her knees up or squatting. After opening the folds of skin around 
the vagina, she will gently squeeze the ring into an oval shape and push it upwards and 
backwards towards the back as far as it will go, thereby depositing the ring in the vagina. 
She will then be instructed to thoroughly wash her hands again. At all research centre 
visits during which a pelvic examination is performed, the participant will remove the ring 
prior to the examination. 
If the participant requests help with either removal or insertion of the vaginal ring, or after 
she has made several attempts to remove/insert the ring without success, trained trial staff 
may give assistance. Re-education of the participant on ring removal/re-insertion will be 
given. This will be noted in the source documents and applicable CRFs. Additional 
instructions about ring use will be provided in the SOM. 
All rings that are removed will be inspected visually, and an assessment will be made by 
the principal investigator or designee as to whether the ring appears to have been used 
or not, together with a reason for the assessment. The rings should then be rinsed in 
running water, patted dry, placed in a ring return bag, and stored between 15°C and 30°C 
until shipment to the analytical laboratory for testing of residual dapivirine amounts. 
5.15. 
Vaginal Ring Adherence Counselling 
At the Enrolment and Trial Visits, participants will receive vaginal ring adherence 
counselling, including adherence to trial visit schedule and requirements. At the Enrolment 
Visit, IPM 032 participants will be provided with feedback on the IPM 027 and MTN-020 
trials, which will include information on trial adherence trends, as part of the vaginal ring 
adherence counselling. Research centre staff will counsel participants to refrain from 
removing the ring (except as directed during research centre visits) and will provide 
instructions to all participants in case of accidental ring expulsion (e.g., during sex or 
exercise), or removal, and guidance will be provided on how the ring should be handled 
when it is out of the vagina. Research centre staff will also provide instructions to the 
participants during the 3-monthly trial visit period for insertion of a new ring after a month 
and the participants will be counselled on how to store the used and unused rings at home, 
if applicable.  
If, for any reason, the participant is non-adherent to the use of the vaginal ring (i.e. she 
removes the ring for any purpose other than as instructed at a trial visit), this should be 
documented according to the guidelines specified in the SOM.  
5.16. 
Qualitative Behavioural Assessments 
In cases of interest IDIs will be conducted; approximately three participants will be 


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interviewed per site. These cases of interest may include, but will not be limited to 
participants who may have experienced social harms, may have had problems using the 
ring, or who HIV seroconverted. 
These assessments will provide data on acceptability and influencers of ring use. The 
recruitment and sampling strategy will be specified in the study operations manual. 
5.16.1. Participant Questionnaire 
The Participant Questionnaire will be administered at every trial visit and the LPUV 
This questionnaire includes acceptability questions about the monthly and 3-monthly 
research centre follow-up during the trial.  
5.17. 
Sample Storage and Analysis 
Blood (blood volume as specified in Appendix C) and vaginal fluid samples will be 
collected for storage locally or at a central laboratory at all research centre visits. Blood 
samples for HIV-1 RNA PCR, genotype (including NGS) and phenotype resistance testing 
will be stored at the Screening Visit, the Enrolment Visit, every Trial Visit, LPUV and Exit 
Visit and will be tested subsequent to confirmed HIV-1 seroconversion, according to the 
HIV testing algorithm described in Section 5.4. HIV-1 RNA PCR will be performed on 
samples stored at last product use visit and on the last samples collected for participants 
who discontinue from the trial without an exit visit. Only samples from participants who 
consented for analysis will be selected for the additional HIV-1 RNA PCR analysis and 
additional HIV viral genotype (including NGS) and phenotype resistance testing as 
needed. Testing will also be conducted on a random sample of HIV-negative participants. 
For possible dapivirine concentration measurements, plasma and vaginal fluid samples 
should preferably be collected prior to removal of the vaginal ring. Further details regarding 
these procedures will be provided in the Laboratory Manual, as part of the SOM. 
All specimens will be collected and analysed according to methods described in the 
Laboratory Manual and research centre SOPs for proper collection, processing, labelling, 
and transport of specimens to the laboratories conducting the analysis. Where possible 
and appropriate, stored specimens will be re-tested to assess validity of unusual or 
unexpected assay results. 
Any residual specimens will be stored at least until the first marketing authorization by a 
stringent regulatory authority has been granted. 
5.18. 
Screening Identification (SCR-ID) and Participant Identification (PID) 
Numbers 
After informed consent is obtained, a SCR-ID number will be assigned to each 
participant for identification purposes and the participant will be screened to assess 
eligibility for the trial. As each new participant enters the trial, a unique PID number will 
be assigned in consecutive order, starting with the lowest number available at the research 


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centre at the time. 
5.19. 
Diary cards 
Participants will be provided with diary cards at enrolment and at trial visits, as applicable, 
except the LPUVs and Exit Visits. The diary cards are meant to be completed by the 
participants, and returned to the research centre at each Trial Visit and the LPUV to serve 
as a memory aid for participants to review during their scheduled visits and adherence 
counselling. The diary card will be used to document the removal and insertion date of the 
additional rings and for documenting AEs experienced and concomitant medications taken 
between trial visits. Participants will be requested to document the details of all cases of 
accidental ring expulsion or removal. Additional instructions on diary cards will be provided 
in the SOM. 
5.20. 
Participant Reimbursement 
Participants will be reimbursed for any travel costs incurred in compliance with local 
regulations. Reimbursements will be made after the completion of each trial visit. 
Research centre specific reimbursement amounts will be documented in the trial ICF 
approved by the applicable IRB/IEC. Upfront reimbursement for travel expenses may be 
made if this has been approved by the relevant ethics committee. 
Note: During the 3-monthly trial visit period, participants who choose to not receive the 
two additional vaginal rings during trial visits, will be responsible for the travel costs 
incurred during the optional vaginal ring collection/return visits to the research centre. 
5.21. 
Participant Compensation 
If a participant in an IPM clinical trial becomes ill or injured as a result of participation in 
the trial, medical treatment for the adverse reaction or injury will be provided appropriately. 
The research centre staff will refer the participant for ongoing treatment for the injury, if 
needed. The Sponsor will be responsible for compensation for appropriate medical 
expenses for treatment of any such illness or injury. An HIV infection that occurs during 
the course of the trial will not be considered an injury or illness caused by trial participation. 
5.22. 
Participant Responsibility 
Referral systems to local medical services will be implemented by research centres prior 
to trial start. It remains the participant’s responsibility to follow up with relevant medical 
services once referral has been initiated by the research centre. 
5.23. 
Study Operations Manual (SOM) 
A SOM will be supplied to all research centres to provide general guidance on the conduct 
of trial procedures. The Laboratory Manual is contained within the SOM. 


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6. Investigational Product
6.1. 
Investigational Product Composition 
The dapivirine silicone elastomer vaginal matrix ring is an off-white flexible ring containing 
25 mg of dapivirine dispersed in a platinum-catalysed silicone matrix. The dimensions of 
the ring are 56 mm (outer diameter) and 7.7 mm (cross sectional diameter). The dapivirine 
silicone elastomer vaginal matrix ring is designed to provide sustained release of 
dapivirine over a minimum of one month. 
The Dapivirine Vaginal Ring-004 is comprised of dapivirine, the polydimethylsiloxane 
liquid MED-360 and the silicone MED-4870. The safety of dapivirine has been established 
in a comprehensive nonclinical and clinical development programme described in the IB14. 
Both the silicone elastomers and the liquid silicone dispersant have been evaluated in in 
vitro cytotoxicity, haemolysis tests, cytogenic damage and genotoxicity assays, and in in 
vivo systemic toxicity studies, intracutaneous toxicity studies, pyrogen studies and delayed 
contact sensitisation studies. The silicone elastomer was also evaluated in muscle 
implantation studies of up to 12 weeks duration. In addition, a number of preclinical tests 
were performed on the finished Dapivirine Vaginal Ring-004, including a panel of 
biocompatibility tests (in vitro cytotoxicity and genotoxicity assays, and in vivo vaginal 
irritation and sensitisation studies) using extracts of the ring, and a study in sheep, in which 
Dapivirine Vaginal Ring-004 containing 25 mg dapivirine was inserted into the vagina (up 
to 3 consecutive rings; each ring for a period of 30 days). None of these tests identified 
any significant safety concerns. 
6.2. 
Packaging and Labelling 
IPM will bear the responsibility for primary and secondary packaging and labelling. The 
packaged rings will be labelled according to local regulatory requirements. 
6.3. 
Investigational Product Storage 
The recommended storage condition for the dapivirine ring is 15°C to 30°C, excursions 
permitted. The proposed shelf life is 48 months when stored in the original packaging 
under the recommended storage conditions. In the event that the IP has been subjected 
to different storage conditions than specified above, the affected IP will not be used (unless 
IPM or its designee provides written authorisation for use). IPM should be notified 
immediately in the event that IP storage conditions have been breached. 
The investigator (or pharmacist) will maintain an inventory and acknowledge receipt of all 
shipments of IP. More information on IP storage will be provided in the SOM. 
Participants will be provided with instructions on storage of used and unused rings during 
the 3-monthly trial visit schedule. 
6.4. 
Investigational Product Administration 
The participants will be instructed to self-insert the Dapivirine Vaginal Ring-004 at the 


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Enrolment Visit, and monthly thereafter. The participants will be reminded of proper 
vaginal ring insertion and removal procedures.  
During the 3-monthly trial visit schedule, participants will be instructed to remove the 
vaginal rings and self-insert each of the two additional rings at monthly intervals until their 
next scheduled research centre visit. The self-insertion and removal of the rings should 
take place at the research centres during the months that the participants attend their 
scheduled trial visits. Participants should be advised to continue ring use through menses. 
6.5. 
Investigational Product Expulsion or Loss 
If a participant accidentally expels the ring, e.g., during sex or exercise, she will be 
instructed to rinse the vaginal ring thoroughly in clean water and re-insert the ring as soon 
as possible. If the vaginal ring is expelled and cannot be successfully reinserted, the ring 
should be appropriately rinsed, patted dry and stored in the bag provided for this purpose, 
until the earliest possible opportunity the participant can return for help with the reinsertion 
of a ring at the research centre.  
During monthly visits, if the ring is expelled in such a manner that the participant is 
unwilling to re-insert it, e.g., during urination or a bowel movement, or if the ring is lost, the 
participant should return to the research centre at the earliest possible opportunity to 
receive a replacement ring.  
During the 3-monthly trial visit schedule, participants will be instructed that if the ring is 
expelled in such a manner that the participant is unwilling to re-insert it, e.g., during 
urination or a bowel movement, or if the ring is lost, the participant should use one of the 
unused, additional rings dispensed. If the expelled ring was the last of the additional 
vaginal rings dispensed, the participant should return to the research centre at the earliest 
possible opportunity to receive a replacement ring.  
Also, in cases where a ring is removed due to a genital infection, a new ring will be inserted 
or dispensed. Visits associated with expulsion or loss of rings will be regarded as 
unscheduled visits unless the visit is within the 7-day window period of the next scheduled 
visit. 
6.6. 
Retrieval of Investigational Product 
All participants who are prematurely discontinued from the trial will be encouraged to 
return to the research centre for a final evaluation, at which time all vaginal rings in the 
participant’s possession should be retrieved. If the participant does not return her used or 
unused vaginal ring at this visit, it should be retrieved as soon as possible after this visit, 
either by the participant returning it to the trial staff, or by trial staff conducting a home visit. 
For participants who are considered lost to follow-up and permanently discontinued from 
the trial, reasonable contact attempts will be made according to the locator information 
provided by the participant and local SOPs. Any used or unused vaginal rings that could 
not be retrieved will be documented in the source documents and applicable CRFs. 


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6.7. 
Investigational Product (IP) Accountability 
The principal investigator or designee will be responsible for adequate and accurate 
accounting, handling, storage and dispensing of the IP. The IP will be stored safely and 
properly in a secure location with access available only to the principal investigator and 
designated trial personnel. IP and clinical supplies are to be dispensed only in accordance 
with the protocol. Accurate records of IP received from IPM, the amount dispensed to the 
participants, the amount returned by the participants, the quantity remaining at the 
conclusion of the trial and any wasted or expired IP will be maintained. 
Unused and used rings not analysed for residual amounts of dapivirine will be destroyed 
according to IPM instruction and local regulatory requirements. 
6.8. 
Concomitant Medications and Products 
Prescription and non-prescription medications will be recorded on the source documents 
and applicable CRFs. Vaginal products and practices including the use of spermicides, 
intravaginal medication, douches, lubricants, tampons and female condoms may be used 
during the trial and will be captured. Further details will be provided in the SOM. 
7. Adverse Events
7.1. 
Definition 
An AE is any untoward medical occurrence during the course of a trial in a participant who 
received an IP at any dose, which does not necessarily have a causal relationship with 
the IP. An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom or disease temporally associated with the use of 
an IP, whether or not considered related to the IP. This definition includes inter-current 
illnesses or injuries and exacerbation of pre-existing conditions. 
An unexpected adverse event is an adverse event, the nature or severity (intensity) of 
which is not consistent with the applicable product information (i.e. IB, package insert, or 
summary of product characteristics). Final determination of whether an event is 
considered unexpected will be made by the Sponsor, however, the investigator should be 
knowledgeable of the contents of the IB. 
Whenever possible, the laboratory abnormalities should be considered in the context of 
the primary clinical diagnosis and should be reported as such (e.g. acute hepatitis with 
increased bilirubin). Clinically significant laboratory abnormalities will be considered AEs 
and graded for severity based on the Division of AIDS (DAIDS Table for Grading Severity 
of Adult and Pediatric Adverse Events) as appropriate. 
Any condition occurring prior to enrolment will be reported as a pre-existing condition 
under Medical or Gynaecological History. All AEs occurring during the trial will be recorded 
in the source documents and applicable CRFs. All AEs will be reported and graded 
according to the latest version of the DAIDS Table for Grading Severity of Adult and 
Pediatric Adverse Events and Female Genital Grading Table for Use in Microbicide 
Studies (which will be provided to research centres in the SOM). A vaginal bleeding 


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abnormality thought to be due to contraception, asymptomatic BV and asymptomatic 
candidiasis will not be reported as an AE for this trial. 
If a unifying diagnosis is possible, the investigator should record a specific disease or 
syndrome rather than individual associated signs and symptoms. However, if an observed 
or reported sign, symptom, or clinically significant laboratory abnormality is not considered 
a component of a specific disease or syndrome by the investigator, it should be recorded 
as a separate AE. 
All AEs will be monitored until resolution and/or the cause are identified, or until the 
investigator does not expect any improvement or worsening of condition/symptoms. If a 
SAE, urogenital AE or related AE remains unresolved at the participant’s Exit Visit, the 
research centre investigator will make a clinical assessment with the IPM Clinical 
Physician to determine whether continued follow-up of the AE is warranted. All other AEs 
that are not serious, not urogenital and assessed to be unrelated to IP will be noted as 
ongoing at trial end if the outcome is not yet determined at the time of the exit visit. 
7.2. 
Assessment of Adverse Event Severity 
The investigator is responsible for assessing the severity of AEs occurring on trial. All AEs 
except genital complaints will be graded according to the latest version of the DAIDS Table 
for Grading Severity of Adult and Pediatric Adverse Events. All genital complaints will be 
graded according to the latest version of the Female Genital Grading Table for Use in 
Microbicide Studies, which will be provided to research centres in the SOM. 
For AEs not listed on either of these tables, the following criteria will be used to estimate 
the grade of severity: 
•
Mild
Symptoms causing no or minimal interference with usual social and functional
activities
•
Moderate
Symptoms causing greater than minimal interference with usual social and
functional activities
•
Severe
Symptoms causing inability to perform usual social and functional activities
•
Potentially Life-threatening
Symptoms causing inability to perform basic self-care functions OR medical or
operative intervention indicated to prevent permanent impairment, persistent 
inability, or death
7.3. 
Relationship to Investigational Product 
The investigator is responsible for determining the relationship of all AEs occurring during 


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the trial and will assess AEs based on the following criteria: 
•
Not Related
There is not a temporal relationship or a reasonable possibility of a causal 
relationship (i.e. some level of evidence is lacking) to administration of the
investigational product. The AE is clearly explained by another cause 
(concurrent disease, concomitant medication, environmental or toxic factors,
etc.).
•
Related
There is a reasonable possibility of a causal relationship between the
investigational product and the AE, (i.e. there is some level of evidence as to
the causal association). The event may respond to withdrawal of the
investigational product (dechallenge), and recurs with rechallenge by
administration of the investigational product. In other cases the AE is clearly
related and most likely explained by the administration of the investigational
product.
7.4. 
Serious Adverse Event 
7.4.1. Serious Adverse Event Definition 
A serious adverse event (SAE) or reaction is any untoward medical occurrence that at any 
dose: 
•
Results in death.
•
Is life-threatening.
This criterion applies if the participant is at immediate risk of death from the
event as it occurred, in the opinion of the investigator; it does not refer to an
event which hypothetically might have caused death if it were more severe.
•
Requires in patient hospitalisation or prolongation of existing
hospitalisation.
This criterion applies if the event requires inpatient hospitalisation and results
in an overnight stay in hospital or, if in the opinion of the investigator, prolongs
an existing hospitalisation. A hospitalisation (including hospitalisation for an
elective procedure or routinely scheduled treatment not associated with an
adverse event) for a pre-existing condition which has not worsened does not
constitute an SAE.
•
Results in persistent or significant disability/incapacity.
This criterion applies if the event causes a substantial disruption of a person’s
ability to conduct normal life functions.
•
Is a congenital anomaly/birth defect.
This criterion applies if a participant gives birth to a child with a congenital
anomaly or birth defect or if the anomaly/birth defect is diagnosed by any
prenatal tests.
•
Important medical events.
In a medically significant event that may not be immediately life-threatening or
result in death or hospitalisation but may jeopardize the participant or may 


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require intervention in order to prevent one of the outcomes listed above should 
also be considered serious; e.g., bronchospasm requiring intensive treatment 
in an emergency room or at home. 
NOTE: A SAE does not have to be severe in nature to meet any of the above criteria. 
All SAEs that occur from the time the participant is enrolled through the duration of the 
trial, whether considered associated with the IP or not, must be reported to the IPM 
Medical Safety Physician and/or designee within 24 hours of the centre becoming aware 
of the event. All SAEs should be recorded in the source documents and the relevant CRFs 
and reported using the Immediately Reportable Events (IRE) Form provided. 
The IRE Report Form should be completed with all the available information at the time of 
reporting. The investigator is required to write a detailed report and complete SAE follow 
up in a timely manner until the SAE has resolved, the participant returns to normal health, 
or until the investigator does not expect any further improvement or worsening of the 
condition. Medical Records may be requested by IPM to assist in assessing relatedness 
and severity of the SAE, and for possible submission to the Regulatory or Health 
Authorities as appropriate. To maintain confidentiality, the participant’s name must be 
blacked out on any medical records submitted and replaced with the PID number and the 
initials. 
More details on SAE reporting requirements and processes are described in the Safety 
Reporting Plan (provided in the SOM) provided to the research centres. 
7.4.2. Serious Adverse Event Contact Information 
SAEs will be reported to IPM or designee within 24 hours of any research centre staff 
member becoming aware of the event. If the SAE is related, and life-threatening or fatal, 
IPM Medical Safety should additionally be notified immediately by email or telephone. 
The following email will be used for communication with the IPM Medical Safety team 
regarding any IREs: safetyreports@ipmglobal.org. Contact details of relevant safety 
personnel will be provided in the Safety Reporting Plan. 
IPM or designee will process all safety events. The IPM Medical Safety Physician or 
designee will review all SAEs and generate the necessary queries. Further SAE reporting 
guidelines will be specified in the Safety Reporting Plan. 
7.4.3. Sponsor Notification of SAEs to the Regulatory Authorities 
Any unexpected serious adverse events which are deemed related to investigational 
product, will be considered “associated with the use of investigational product” and, as 
such, IPM will notify the appropriate regulatory authorities of the event in an expedited 
manner unless policies of the local regulatory authorities mandate such reporting by the 
research centre.  
Any unexpected SAE deemed to be unrelated to the IP will not be reported to the 
regulatory authorities in an expedited manner, unless policies of the local regulatory 
authorities mandate such reporting. 


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7.4.4. Research Centre Notification of SAEs to Local Independent Ethics 
Committee or Local Health and Regulatory Authorities 
The investigator will report all SAEs to the local IEC and/or regulatory or health authorities 
in accordance with standard operating procedures and policies of the IEC and/or 
regulatory or health authorities. 
7.5. 
Immediately Reportable Events 
These are events which, while not necessarily meeting criteria for seriousness, are 
considered important by IPM and as such warrant immediate reporting to IPM. The 
following events should be reported to the Sponsor within 48 hours of any research centre 
staff member becoming aware of the event: 
•
Pregnancy: Although not considered an AE, pregnancy must be reported if it
occurs at any time while on IP during the trial;
•
HIV infection any time during the trial;
•
Any non-serious AE (including laboratory abnormalities) leading to permanent
discontinuation of the investigational product.
All IREs that occur from the time the participant is enrolled should be reported to IPM 
within the time periods specified above. All IREs should be recorded in the source 
documents and the relevant CRFs and should be reported to the IPM Medical Safety 
Physician using the IRE Form provided. 
As with SAEs, the IRE form should be completed with all available information at the time 
of reporting. The investigator is required to follow up the IRE in a timely manner until such 
time as it is deemed appropriate by IPM that all relevant information has been collected, 
or until such time as the participant is lost to follow up. 
7.6. 
Safety Monitoring 
The IPM 032 trial team will monitor safety and participant recruitment throughout the trial 
for all participants. Safety data from the trial will be evaluated by an independent Data and 
Safety Monitoring Board (DSMB). The first scheduled meeting will take place 
approximately six months after all research centres have been activated and thereafter at 
approximately annual intervals for the duration of IPM 032. Based on the review of the 
data, the DSMB is required to provide recommendations about continuation, pausing, 
termination or other modifications to the trial, including changes to the information provided 
to participants for obtaining their informed consent. An IPM 032 DSMB charter will 
describe the roles and responsibilities of the DSMB, its composition, data to be provided 
to the DSMB, the process for disseminating trial data to the DSMB, and the communication 
plan between the DSMB and IPM. 
7.7. 
Data Handling at Research Centres 
All trial data will first be collected on designated source documents and then recorded on 
CRFs with the exception of the Participant Questionnaire, for which the CRFs will serve 


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as the source document, unless otherwise specified by IPM. Research centre staff 
responsible for completing the CRFs will receive appropriate training prior to the start of 
the trial, and will follow standardised procedures. Data must be legibly entered onto the 
CRFs. Data corrections will be made in accordance with standard procedures provided by 
IPM or its designee. Instructions for CRF completion will be provided on the back of the 
CRF pages, as well as in the SOM.  
The investigator will maintain, and store in a secure manner, complete, accurate and 
current trial records throughout the trial. Standard GCP practices will be followed to ensure 
accurate, reliable and consistent data collection. 
7.8. 
Source Data Verification 
All trial data must be verifiable to the source documentation (which includes original 
recordings, laboratory requisitions and reports, medical records, etc.). Source 
documentation will be made available to the IPM or representative(s) for review to ensure 
that the collected data is consistent with CRFs and has been completely and accurately 
reported as required by the trial protocol. 
8. Statistical Methods
IPM 032 is a Phase IIIb, multi-centre, open-label follow-on trial to IPM 027 to evaluate the 
safety of and adherence to Dapivirine Vaginal Ring-004, inserted at monthly intervals in 
healthy, HIV-negative women who have participated in the IPM 027 trial.  
Individuals meeting all inclusion criteria and no exclusion criteria will be eligible to receive 
the Dapivirine Vaginal Ring-004 with monthly research centre follow-up for one month 
(which may be extended to three months at the investigator’s discretion) followed by 
3-monthly research centre follow-up visits.
Up to 1400 participants from the IPM 027 trial are expected to be enrolled in the trial. 
Participants will self-insert the vaginal rings. Once participants commence the period of 
3-monthly follow up visits, two additional rings will be dispensed at each trial visit, the first
of which the participants should self-insert one month later, and the second ring one month 
after that, before returning to the research centre for their next scheduled visit.
An exit visit will be conducted approximately 1-2 months after removal of the last ring (last 
product use visit). 
8.1. 
Trial Endpoints 
The primary, secondary and exploratory trial endpoints are described in detail in 
Section 2.2 of the protocol. 
8.2. 
Primary Trial Hypotheses 
From previous clinical and safety trials of dapivirine, it is now known that the Dapivirine 


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Vaginal Ring-004 is well-tolerated and reduces the risk of acquiring HIV-1 infection. These 
results also showed little to no risk reduction of HIV-1 infection in younger women (aged 
18-21 years).
8.3. 
Sample Size and Power Calculations 
This trial will be conducted in healthy, HIV-negative women. who have participated in the 
IPM 027 trial. No formal sample size or power calculations have been performed. It is 
expected that up to 70% of the participants enrolled in IPM 027 will participate in this trial. 
Therefore, a total sample size of up to 1400 HIV-negative women is anticipated.  
8.4. 
Statistical Analyses 
The primary analysis will focus on safety as well as adherence assessments. 
The primary analysis will be performed under the intent-to-treat (ITT) principle, which will 
include all participants enrolled in the trial. As it is possible that the inclusion of non-
adherent participants or participants who discontinued from the IP may artificially lower 
the rates of safety outcomes, additional analyses will be conducted on the per-protocol 
population, which will include only participants who were adherent to the protocol. Details 
on the definition of the per-protocol population, in addition to models that will be used to 
examine the exploratory objectives and other technical aspects of these analyses will be 
provided in a SAP, which will be finalised prior to final database lock. 
The analysis of the secondary safety assessments will be mainly descriptive in nature. 
The incidence density rate of HIV-1 seroconversion and the frequency of HIV-1 drug 
resistance in women who seroconvert will be summarised descriptively. 
The data will be presented using appropriate statistical measures including, but not limited 
to: mean, standard deviation, median, and interquartile range for continuous data; 
frequency and relative frequency for categorical data. When appropriate, 95% confidence 
intervals will be presented. 
8.4.1. Primary Safety Analysis 
A descriptive analysis of all AEs will be presented in tables and listings. AEs will be 
summarised by MedDRA System Organ Class (SOC) and Preferred term (PT). The 
proportion of participants experiencing adverse events, including the proportion of 
participants experiencing product-related adverse events, Grade 3 or 4 AEs, or SAEs, will 
be determined, and presented with corresponding 95% CIs. 
All data will be presented by research centre, and overall across research centres. 
8.4.2. Primary Adherence Analysis 
Residual levels of dapivirine in returned rings and/or plasma and/or vaginal fluid 
concentrations of dapivirine will be used as measures of adherence to ring use. The data 
will be listed, summarised and presented graphically. The ring residual levels and/or 
plasma and/or vaginal fluid concentrations of dapivirine associated with non-adherence 


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will be informed by the results from IPM 027, and will be described in detail in the SAP, 
which will be finalised prior to final database lock. The correlation between the amount of 
residual dapivirine in the used rings and the corresponding plasma and/or vaginal fluid 
levels of dapivirine will be explored graphically and summarised descriptively. 
8.4.3. Secondary Analyses 
8.4.3.1. 
Incidence of HIV-1 seroconversion 
The incidence of HIV-1 seroconversions, the incidence density rate of HIV-1 
seroconversion, i.e. HIV-1 seroconversion rate per 100 woman-years of product use at 
the end of the ring use period, as well as a 95% CI for the HIV-1 seroconversion rate per 
100 woman-years based on the normal approximation of the Poisson distribution will be 
presented for each research centre, and overall. Kaplan-Meier curves will be presented, 
overall and by research centre. 
8.4.3.2. 
HIV-1 drug resistance 
The results of the genotype (including NGS) and phenotype resisting analyses will be 
primarily descriptive in nature, and will depend on the pattern of resistance mutations 
observed in the HIV-1 seroconverters. The resistance associated mutations observed will 
be listed by participant, and a frequency tabulation of individual resistance mutations 
associated with the various classes of antiretrovirals, e.g. Protease Inhibitors, Nucleoside 
Reverse Transcriptase Inhibitors and Non-nucleoside Reverse Transcriptase Inhibitors, 
will be produced. The proportion of HIV-1 seroconverters with at least one HIV-1 drug 
resistant mutation will be presented, with the corresponding 95% CI. 
8.4.4. Other results from Qualitative/Quantitative Behavioural assessments 
In cases of interest IDIs will be conducted; approximately three participants will be 
interviewed per site. These cases of interest may include but will not be limited to 
participants who may have experienced social harms, may have had problems using the 
ring, or who HIV seroconverted.  
These assessments will provide data on acceptability and influencers of ring use and will 
be summarised. 
8.4.5. Interim Analysis 
No interim analysis is planned for this trial. However, IPM will review the treatment 
emergent safety data at regular intervals during the conduct of the trial. 
8.5. 
Data and Safety Monitoring Board 
Safety data from the trial will be evaluated by an independent Data and Safety Monitoring 
Board (DSMB). The first scheduled meeting will take place approximately six months after 
all research centres have been activated and thereafter at approximately annual intervals 
for the duration of IPM 032. Based on the review of the data, the DSMB is required to 
provide recommendations about continuation, pausing, termination or other modifications 
to the trial, including changes to the information provided to participants for obtaining their 


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informed consent. An IPM 032 DSMB charter will describe the roles and responsibilities 
of the DSMB, its composition, data to be provided to the DSMB, the process for 
disseminating trial data to the DSMB, and the communication plan between the DSMB 
and IPM. 
8.6. 
Handling of Missing Data and Dropouts 
Some degree of missing data, primarily associated with missed visits, is expected. The 
amount of missing data will be explored and incorporated into the analyses, where 
appropriate. For the analysis of adherence to monthly ring use, patterns of missing data 
may be informative. Depending on the proportion of participants who discontinue early, an 
analysis of time to discontinuation may be conducted. Such an analysis would allow 
investigation of the covariates associated with early discontinuation and could provide 
information that would be useful in designing future trials of other microbicide rings. 
Patterns of missing data may also provide further insight into participants’ preference for 
monthly or 3-monthly follow-up visits to research centres. 
9. Investigator Requirements
9.1. 
Trial Initiation
The trial can be initiated at the research centre once all relevant IRB/IEC and regulatory 
approvals have been obtained in compliance with country specific requirements, and the 
relevant essential documents are available on file. Following IPM approval, IPM will notify 
the research centre in writing via letter correspondence to begin trial operations according 
to the protocol. 
9.2. 
Institutional Review Boards or Independent Ethics Committee 
Approval 
This protocol, the informed consent document, and relevant supporting information will be 
submitted to the IRBs/IECs for review and must be approved before the trial is initiated. 
The principal investigator is responsible for communicating with IRBs/IECs regarding the 
progress of the trial and changes made to the protocol as deemed appropriate, at least 
once a year. The principal investigator will also keep the IRBs/IECs informed of any 
significant AEs and SAEs, in accordance with standard operating procedures and policies 
of the IRB/IEC. 
9.3. 
Trial Monitoring and Audits 
Trial monitors will regularly visit participating research centres to review trial documents 
including, but not limited to individual participant records, consent forms, source 
documents, CRFs, supporting data, laboratory specimen records and medical records 
(physicians’ progress notes, nurses’ notes, individuals’ hospital charts) to ensure 
protection of trial participants, compliance with the protocol, and accuracy and 
completeness of records. The trial monitors will also inspect the research centre’s 


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regulatory files to ensure that regulatory requirements are being followed; the research 
centre’s pharmacies to review product storage, management, and drug accountability; and 
the research centre’s laboratory and other clinical supplies to ensure proper storage and 
continued viability of supplies. All applicable trial documents should be readily available 
for review during the visits. The trial monitors will also check that clinical trial procedures 
are observed and will discuss any problems with investigator or designee as applicable. 
During or after the clinical trial, the governmental regulatory authorities, local IRB/IEC 
and/or representatives of the IPM may request access to all trial documents for on-site 
research centre audit or inspection. 
9.4. 
Case Report Forms (CRFs) 
CRFs will be supplied by IPM or its designee and will be handled in accordance with 
instructions from IPM. 
All CRFs will be completed by the designated trial staff in accordance with the instructions 
provided by IPM. Upon trial completion, the CRF is reviewed, signed, and dated by an 
investigator listed on the Statement of Investigator, Form FDA 1572. 
All CRFs will be completed in a neat, legible manner to ensure accurate interpretation of 
data. Black ink is required to ensure clarity. When making changes or corrections, the 
original entry will be crossed out with a single line, and the change initialed and dated. 
Erasures, overwriting, and correction fluid are NOT allowed on the CRFs. 
9.5. 
Disclosure of Data 
Participant medical information is confidential and disclosure to third parties other than 
those described in Section 9.3 is strictly prohibited. All trial data will be stored securely at 
the research centre. All participant information including laboratory reports, forms, lists, 
logbooks, appointment books and administrative forms will be stored in locked file cabinets 
or rooms in areas with access limited to trial staff. 
Participants’ trial information will not be released without written permission of the 
participant, except as necessary for monitoring by IPM, IPM’s designated monitors, 
regulatory authorities, or local IRBs/IECs. 
9.6. 
Record Retention 
The principal investigator will retain in a secure manner, complete, accurate and current 
trial records for a minimum of two years after marketing approval or termination of product 
development. Trial records include administrative documentation, including research 
centre registration documents and all reports and correspondence relating to the trial, as 
well as documentation related to each participant screened and/or enrolled in the trial, 
including ICFs, CRFs, notations of all contacts with the participant, and all other source 
documents. All records must be retained on-site throughout the trial’s period of 
performance. IPM will provide the research centre with written instructions for long-term 
record storage at the completion of the trial. 


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No records should be destroyed without prior written permission from IPM. 
10. Ethical Considerations
10.1. 
Ethical Review 
This protocol, research centre-specific informed consent documents, participant 
education, outreach, recruitment materials and any other requested documents or 
subsequent modifications will be reviewed and approved by the ethical review bodies 
responsible for oversight of research conducted at the research centre. 
Subsequent to initial review and approval, the local IRB and/or IEC will be notified about 
trial completion within three months following trial termination or completion. This trial will 
be conducted in accordance with: 
•
World Medical Association Declaration of Helsinki17
•
ICH GCP guidelines18
•
Applicable national ethics and regulatory requirements in countries where the
trial is being conducted, e.g. Guidelines for Good Practice in the Conduct of
Clinical Trials in Human Participants in South Africa 19.
10.2. 
Reporting and Management of Social Harms related to trial 
participation 
Social harms, e.g., disruption of family or personal relationships may result due to 
participation in this trial becoming known to others. In addition, IP use could potentially be 
unacceptable to the participant’s sex partner and result in difficulties with her sex partner. 
If a participant is or becomes HIV-infected, she may also experience social harms. 
During each HIV counselling session, enrolled participants will be asked questions to 
assess the occurrence of social harms related to trial participation. Participants who 
experience social harms considered to be related to trial participation will be counselled 
accordingly and provided with assistance to mitigate the circumstances if possible. This 
will be recorded in the source documents and applicable CRFs. 
10.3. 
Community Engagement 
Community Liaison Officers have been appointed at each research centre to oversee the 
information provided to local stakeholders, target population and general community. They 
have been tasked with capturing, monitoring and evaluating feedback from the community. 
Comments will be captured in various ways at each research centre using methods such 
as suggestion boxes, door-to-door campaigns, large and small community dialogue 
sessions, pre/post-tests, distributed feedback forms, etc. Each research centre has a 
process for consulting with its community. The primary vehicle for this consultation is 
through formal structures such as the Community Advisory Boards/Groups/Committees. 
These systems allow investigators and communities to identify and respond rapidly to 
concerns raised. 


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11. Publications
Any presentation, abstract, or manuscript shall be reviewed and approved by the Sponsor 
prior to submission. Publication of the results of this trial will be governed by the IPM’s 
clinical trial agreement with the investigator. Authorship criteria will be based on 
contributions to the design, work, and analysis of the trial. 


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12. References
1. Nel A, Van Niekerk N, Kapiga S, et al. Safety and Efficacy of a Dapivirine Vaginal
Ring for HIV Prevention in Women. N Engl J Med, 2016 Dec 1; 375: 2133-2143.
2. Baeten JM, Palanee-Phillips T, Brown ER, Schwartz K, et al. Use of a Vaginal
Ring Containing Dapivirine for HIV-1 Prevention in Women. N Engl J Med. 2016
Dec; 375(22): 2121–2132.
3. Regional Fact Sheet 2012. Sub-Saharan Africa.
http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2
012/gr2012/2012_FS_regional_ssa_en.pdf
4. AIDS by the numbers; UNAIDS 2013.
http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspublicati
on/2013/20131120_AIDSbynumbers_A5brochure_en.pdf
5. Ombati M. The Feminization of HIV in Sub-Saharan Africa. Africa Policy Journal,
2012.
6. UNAIDS, HIV Prevention among adolescent girls and young women, 2016,
UNAIDS: Geneva, Switzerland.
7. UNAIDS, AIDS By the Numbers- 2016, 2016, UNAIDS: Geneva, Switzerland
8. UNAIDS, 2016 UNITED NATIONS POLITICAL DECLARATION ON ENDING
AIDS SETS WORLD ON THE FAST-TRACK TO END THE EPIDEMIC BY 2030,
2016, UNAIDS: New York, NY/ Geneva, Switzerland.
9. Elias CJ, Coggins C. Female-controlled methods to prevent sexual transmission
of HIV. AIDS 1996;10:S43-S51
10. Karim SSA, Richardson BA, et al. Safety and effectiveness of BufferGel and
0.5% PRO2000 gel for the prevention of HIV infection in women. AIDS 2011;
25(7):957.
11. Nel A, Kapiga S, Bekker LG, et al. Safety and Efficacy of Dapivirine Vaginal Ring
for HIV-1Prevention in African Women. Abstract number 110LB at Conference on
Retroviruses and Opportunistic Infections2016: Boston, MA.
12. Baeten JM, Palanee-Phillips T, Brown ER, et al. A Phase III Trial of the
Dapivirine Vaginal Ring for HIV-1 Prevention in Women. Abstract number 109LB
at Conference on Retroviruses and Opportunistic Infections (CROI) 2016, CROI:
Boston, MA.
13. Brown E, Palanee-Philips T, Marzinke M. et al. Residual dapivirine ring levels
indicate higher adherence to vaginal ring is associated with HIV-1 protection.
AIDS Conference 2016, Durban, South Africa.
14. Dapivirine Vaginal Ring Investigator’s Brochure, Version 10.0, 09 March 2016.


IPM 032 
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15. IPM 011; Clinical Study Report; Version 1.0, 15 March 2011.
16. IPM 015; Clinical Study Report; Version 1.0, 06 July 2012.
17. World Medical Association Declaration of Helsinki. Ethical Principles for Medical
Research Involving Human Subjects; WMA General Assembly, Fortaleza, Brazil,
October 2013. http://www.wma.net/en/30publications/10policies/b3/index.html
18. Guidance for Industry: E6 Good Clinical Practice: Consolidated Guidance.
http://www.fda.gov/downloads/Drugs/Guidances/ucm073122.pdf
19. Guidelines for Good Practice in the Conduct of Clinical Trials in Human
Participants in South Africa. http://www.kznhealth.gov.za/research/guideline2.pdf


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APPENDIX A: SCHEDULE OF PROCEDURES 
Visits 
Screening 
Enrolment 
Trial Visits 
LPUV 
Exit Visit 
As needed 
Trial Months 
Screening 
must occur 
within 45 
days of 
enrolmentk
0 
Months 1-11h,i 
Month 12i
Months 13-
14i
Informed Consent  
X 
Comprehension Assessment 
X 
Assign Screening Identification Number 
X 
Assign Participant Identification Number  
X 
Demographics 
X 
Medical History 
X 
X 
Concomitant Medication Evaluation 
X 
X 
X 
X 
X 
X 
Inclusion/Exclusion Criteria  
X 
X 
Locator Information 
X 
X 
X 
X 
Basic Menses Information 
X 
X 
X 
X 
Physical Examination 
X 
X 
X 
Adverse Event Evaluation 
X 
X 
X 
X 
X 
Social Harms Assessment 
X 
X 
X 
X 
X 
Pelvic Exam 
X 
X 
X 
Vaginal Ring Dispensing and Insertion 
X 
X 
Vaginal Ring Return/Collection 
X 
X 
Visual Inspection of Returned Ring(s) 
X 
X 
Provision of Vaginal Ring Use and Storage Instructions 
X 
X 
Vaginal Ring Adherence Counselling 
X 
X 
Provision of Diary Card(s) 
X 
Xj
Collection of Diary Card(s) 
X 
X 
Participant Questionnaire 
Xa
X 
In-depth individual interviews l 
Xl 
HIV/STI Risk Reduction Counselling 
X 
X 
X 
X 
X 
Contraceptive Counselling 
X 
X 
X 
X 
X 
X 
Provision of and/or referral for Contraceptives 
X 
X 
X 
X 
X 
X 
Provision of Male and/or Female Condoms (if participant 
wishes to receive them) 
X 
X 
X 
X 
X 


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Visits 
Screening 
Enrolment 
Trial Visits 
LPUV 
Exit Visit 
As needed 
Trial Months 
Screening 
must occur 
within 45 
days of 
enrolmentk
0 
Months 1-11h,i 
Month 12i
Months 13-
14i
Urine Pregnancy Test (hCG)  
X 
X 
X 
X 
X 
Cervicovaginal Sample 
Collection 
for 
STI 
Tests 
Trichomonas vaginalis (TV), Neisseria gonorrhoeae (NG) 
and Chlamydia trachomatis (CT) 
X 
X 
X 
Provision of treatment and/or referral for STIs and Other 
Findings 
X 
HIV Pre- & Post-Test Counselling 
X 
X 
X 
X 
X 
HIV Rapid Tests b 
X 
X 
X 
X 
X 
X 
HIV-1 RNA PCR Test c, d 
X 
X 
X 
X 
X 
Plasma Viral Genotype (including NGS) and Phenotype 
Sample c, d 
X 
X 
X 
X 
X 
Plasma Dapivirine Concentrations 
X 
X 
Vaginal Fluid Dapivirine Concentrations 
X 
X 
Laboratory Testing for Safety Assessments e 
X 
X 
Urine Dipstick Analysis (Urine Microscopy if Clinically 
Indicated Only) 
X 
X 
RPR f 
X 
Cervical Sample Collection for Cytology g 
X 
X 
Final Laboratory results provided 
X 
a) 
Participant Questionnaire w ill be administered at all Trial Visits.
b) 
Performed in accordance with HIV testing algorithm.
c) 
Sample w ill be stored and w ill only undergo testing subsequently or after confirmation of seroconversion and at every visit for seroconverters, or if required by HIV testing
algorithm.
d) 
Sample w ill be obtained at the point of tw o reactive HIV rapid tests and analysed subsequently or after confirmation of seroconversion.
e) 
Blood draw  by venepuncture for laboratory testing (haematology and chemistry). Haematology w ill include full blood counts, differential, and platelet count. Chemistry tests w il 
include creatinine, AST and ALT.
f) 
TPHA/TPPA should be performed if RPR positive.
g) 
Cervical sample collection for cytology may be conducted at any trial visit if no result is evident w ithin the previous year, or abnormal at last cervical cytology.
h) 
All w omen w ill attend a research centre follow-up visit one month after enrolment. Follow ing this visit, at investigator’s discretion, a participant can continue on a 3-monthly
visit schedule. Monthly visits may how ever be extended up to the first three months of participation.
i)
IPM w ill have the option to extend the trial period.
j)
Participants w ill receive a diary card at enrolment and at trial visits, as applicable. Returned diary cards will be review ed at all scheduled trial visits.


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k)
Only procedures in bold italics required for participants rolling over directly from LPUV at IPM 027 to IPM 032.
l)
In-depth individual interview s will be conducted amongst selected participants.


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APPENDIX B: HIV TESTING ALGORITHM 
Figure 1: Screening Algorithm 
Not eligible for 
enrolment; 
Refer for appropriate 
counselling and care 
TEST 1 
Non-reactive 
HIV-seronegative 
Discordant 
TEST 3 
Reactive 
HIV-seropositive 
Non-reactive 
HIV-seronegative 
Potentially eligible 
for enrolment 
Potentially eligible 
for enrolment 
TEST 2 
Reactive 
HIV-seropositive 
t 
[ 
] 


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Figure 2: Pre-Enrolment Algorithm 
Not eligible for 
enrolment; 
Refer for appropriate 
counselling and care 
TEST 1 
Non-reactive 
HIV-seronegative 
Discordant 
TEST 3 
Reactive 
HIV-seropositive 
Non-reactive 
HIV-seronegative 
Perform PCR Test 
If undetectable: 
Enrol; 
Sample for storage 
taken 
Enrol 
Sample for storage 
taken 
TEST 2 
Reactive 
HIV-seropositive 
If detectable: 
Not eligible for 
enrolment; 
Counsel as 
appropriate 


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Figure 3: Trial Visits Algorithm 
Reactive 
HIV-seropositive 
Undetectable HIV-1 RNA PCR result: 
Not infected; Continue IP  
 
HIV testing performed only at scheduled visits even 
if same pattern of discordant results continues 
TEST 1 
Non-reRefer for 
appropriate 
counselling and
TEST 3 
Continue IP 
Sample for storage 
taken 
TEST 2 
Discontinue IP;  
Draw sample for 
endpoint confirmation 
by WB and other 
confirmatory tests; 
Analysis of stored 
samples 
Reactive 
HIV-seropositive 
Detectable HIV-1 RNA Continue IP 
and repeat testing in 2 weeks 
 
Refer for appropriate counselling and care; 
Option to enrol in seroconverter protocol 
Continue IP and 
repeat testing in 2 
weeks 
Discordant 
At 2-week follow up visit: 
If same pattern of HIV rapid test results (discordant), 
collect a sample for quantitative HIV-1 RNA PCR 
Non-reactive 
HIV-seronegative 
..___ [ ___ 
] 


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Figure 4: LPUV Algorithm1 
1 HIV-1 RNA PCR will be performed on samples stored at last product use visit and on the last samples collected for participants who discontinue from the trial 
without an exit visit. Only samples from participants who consented for analysis will be selected for the additional HIV-1 RNA PCR analysis and additional HIV viral 
genotype (including NGS) and phenotype resistance testing as needed. 
TEST 1 
Non-reactive 
HIV-seronegative 
Discordant 
TEST 3 
Reactive 
HIV-seropositive 
Non-reactive 
HIV-seronegative 
HIV-negative 
Sample for storage 
taken 
TEST 2 
Draw sample for 
endpoint confirmation 
WB;  
Analysis of stored 
samples 
Reactive 
HIV-seropositive 
Refer for appropriate 
counselling and care; 
Option to enrol in 
seroconverter protocol 


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Figure 5: Exit Visit Algorithm2 
2 HIV-1 RNA PCR will be performed on samples stored at last product use visit and on the last samples collected for participants who discontinue from the trial 
without an exit visit. Only samples from participants who consented for analysis will be selected for the additional HIV-1 RNA PCR analysis. 
Refer for appropriate 
counselling and care 
TEST 1 
Non-reactive 
HIV-seronegative 
Discordant 
TEST 3 
Reactive 
HIV-seropositive 
Non-reactive 
HIV-seronegative 
HIV-negative 
TEST 2 
Draw sample for 
endpoint confirmation 
WB; 
Analysis of stored 
samples 
Reactive 
HIV-seropositive 
( 
) 


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APPENDIX C: VISIT SCHEDULE AND APPROXIMATE BLOOD VOLUMES 
Visit 
Test and 
volume 
(mL) 
Test and 
volume 
(mL) 
Test and 
volume 
(mL) 
Test and 
volume 
(mL) 
Test and 
volume 
(mL) 
Total 
Blood 
Volume 
Screening 
HIV rapid* 
5 mL 
Chemistry 
5 mL 
Haematology 
5 mL 
RPR 
5 mL 
HIV viral 
genotype 
resistance#  
10 mL 
HIV PCR# 
5 mL 
35mL 
Enrolment 
HIV rapid 
5 mL 
HIV viral 
genotype 
resistance#  
10 mL 
HIV PCR# 
5 mL 
20 mL 
Trial Visits 
HIV rapid 
5 mL 
Dapivirine 
levels 
6 mL 
HIV viral 
genotype 
resistance#  
10 mL 
HIV PCR# 
5 mL 
26 mL 
LPUV 
HIV rapid 
5 mL 
Dapivirine 
levels# 
6 mL 
HIV viral 
genotype 
resistance#  
10 mL 
HIV PCR# 
5 mL 
26 mL 
Exit Visit 
HIV rapid^ 
5 mL 
HIV viral 
genotype 
resistance## 
10 mL 
HIV PCR# / 
##
5 mL 
5 mL or 
15 mL## 
Seroconverter 
tests+ 
Western 
blot 
5mL 
Dapivirine 
levels++ 
6 mL 
HIV viral 
genotype 
resistance#  
10 mL 
HIV PCR# 
5 mL 
20 mL++ or 
26 mL 
•
* Depending on the research centre SOP on HIV testing, sampling may be performed by finger
prick or venepuncture.
•
# Stored plasma samples; tested retrospectively to evaluate different parameters at the time of
seroconversion.
•
## Blood samples for HIV-1 RNA PCR, genotype (including NGS) and phenotype resistance
testing will be collected at the scheduled exit visit following seroconversion.
•
^ HIV rapid testing will not be conducted at the scheduled exit visit following seroconversion.
•
+ At the point of seroconversion, these samples will be collected and tested in addition to relevant
visit-specific tests, but no samples should be duplicated during the same visit. No additional
storage samples will be collected.
NOTE: Additional tests may be also performed, as required.
•
++ Test sample for possible dapivirine measurements will not be required if the seroconversion
occurs at the Exit Visit.


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APPENDIX D: TRIAL DESIGN 
MONTH 12 
RING USE DISCONTINUED 
 
DAY 0 
RING INSERTION 
LPUV 
EXIT VISIT 
1-2 months
≤ 45 days 
Monthly trial visit schedule 
First month after enrolment 
(or up to 3 months after 
enrolment at investigator’s 
discretion) 
3-monthly trial visit schedule
2 additional rings dispensed at each trial 
visit, or dispensed as arranged 
ENROLMENT 
Approximately 
1400 women 
SCREENING 
• 
.....________,.()1-------~>0L------~)o ·---------.) •