Sectin 5. Study Prcedures 5.1 Visit Lcatins... 1 5.2 Eligibility Determinatin... 1 5.3 Screening Visit... 2 5.3.1 Screening and Enrllment Timeframe... 2 5.3.2 Screening Visit Prcedures... 2 5.3.3 Screening and Enrllment Lg... 3 5.3.4 Participants Fund t be Ineligible (Screen Failures)... 3 5.4 Enrllment Visit... 4 5.4.1 Enrllment Visit Prcedures... 4 5.5 Fllw-up Visits... 5 5.5.1 Types f Fllw-up Visits... 5 5.5.2 Fllw-up Visit Scheduling... 6 Target Visit Dates... 6 Visit Windws... 6 Visits Cnducted Over Multiple Days: Split Visits... 6 Missed Visits... 7 5.5.3 Fllw-up Visit Prcedures... 7 5.5.4 Visit 7 Cntact/Terminatin Cnsideratins... 8 5.5.5 Participants Wh Becme Infected with HIV... 9 5.5.6 Participants Wh Permanently Discntinue Study Prduct fr Other Reasns... 9 5.5.7 Criteria fr Early Terminatin f Study Participants... 9 This sectin prvides infrmatin n requirements fr study prcedures in MTN-033, including screening, enrllment and participant fllw-up visits. 5.1 Visit Lcatins Given the nature f study prcedures required t be perfrmed during MTN-033, all visit prcedures are expected t ccur at the study clinic r by phne (fr the designated cntact ne week fllwing Visit 6). 5.2 Eligibility Determinatin It is the respnsibility f the site Investigatr f Recrd (IR) and ther designated staff t ensure that nly participants wh meet the study eligibility criteria be enrlled in the study. The study site must establish a standard perating prcedure that describes hw study staff will fulfill this respnsibility. This SOP shuld cntain, at a minimum, the fllwing elements related t eligibility determinatin prcedures, including: During-visit eligibility assessment prcedures Pst-screening visit eligibility assessment and cnfirmatin prcedures (i.e. review f labratry results) Final cnfirmatin and sign-ff prcedures prir t enrllment/randmizatin Dcumentatin f each eligibility criterin (met r nt met) Ethical and human subjects cnsideratins Staff respnsibilities fr the abve (direct and supervisry) QC/QA prcedures (if nt specified elsewhere) Sectin 5 Prtcl Versin 2.0, dated 08 December 2017 Page 5-1
5.3 Screening Visit The term screening refers t all prcedures undertaken t determine whether a ptential participant is eligible t take part in MTN-033. Required screening prcedures are listed in prtcl Sectins 7.2 The study eligibility criteria are listed in prtcl Sectins 5.2 and 5.3. All eligibility criteria are initially assessed at the Screening visit. These same criteria, in additin t thers, are cnfirmed n the day f Enrllment (Visit 2). The Eligibility Checklist prvides further peratinal guidance n the timing f assessment and surce dcumentatin fr each eligibility criterin. This checklist can be fund n the MTN-033 webpage under Study Implementatin Materials. 5.3.1 Screening and Enrllment Timeframe All prtcl-specified screening and enrllment prcedures must take place up t 30 days prir t enrllment/randmizatin, beginning n the day the ptential participant prvides written infrmed cnsent. The day the screening infrmed cnsent is signed is cunted as -30 and enrllment is cunted as Day 0. The screening prcess starts as sn as the participant signs the infrmed cnsent frm, even if n ther screening prcedures were dne n that day. Per prtcl Sectin 7.2, multiple screening visits (as part f the same screening attempt) may be cnducted if needed, t cmplete all required prcedures. In cases where the Screening visit is cnducted ver multiple days, all prcedures are cnsidered part f the same screening visit/screening attempt. Ptential participants may screen fr MTN-033 up t tw times (tw attempts). The term screening attempt is used t describe each time a participant screens fr the study (i.e., each time s/he prvides written infrmed cnsent fr participatin in the study). Nte: When rescreening participants, all screening prcedures need t be repeated, including the infrmed cnsent prcess. Nte, hwever, a new participant identificatin number (PTID) is nt assigned t the participant in this case. Rather, the riginal PTID assigned at the first screening attempt is used fr any repeat screening attempts, as well as future study visits shuld the participant successfully enrll in the study. If all screening and enrllment prcedures are nt cmpleted within 30 days f btaining written infrmed cnsent, the participant must repeat the entire screening prcess, beginning with the infrmed cnsent prcess. 5.3.2 Screening Visit Prcedures Required screening prcedures are specified in the MTN-033 prtcl sectin 7.2 and reflected in the applicable visit checklist available n the MTN-033 webpage. Listed belw is a brief review f all required screening prcedures which include a series f behaviral eligibility assessments, clinical evaluatins, and labratry tests. Administrative screening visit prcedures include the prvisin f infrmed cnsent, generatin f a PTID, assessment f behaviral eligibility criteria and cmpletin f clinical evaluatins and labratry tests. Lcatr and demgraphic infrmatin will als be cllected. Participants will be reimbursed fr their time, and scheduled fr their enrllment visit, if presumptively eligible. Behaviral eligibility criteria, which are based n self-reprt, may be evaluated by administratin f the Screening Behaviral Eligibility Wrksheet, prvided n the MTN-033 webpage under Study Implementatin Materials. As this wrksheet is designed t be interviewer-administered and serve as a surce dcument, questins must be asked verbatim and participant respnses shuld be recrded directly n the wrksheet. It is suggested that staff administer this questinnaire early in the screening visit, s that mre time-cnsuming clinical and labratry Sectin 5 Prtcl Versin 2.0, dated 08 December 2017 Page 5-2
evaluatins can be avided if the participant is determined ineligible due t behaviral criteria (unless sites decide t administer clinical and labratry evaluatins regardless f eligibility as a service t the participant). Clinical screening visit prcedures, as described in detail in Sectin 7 (Clinical Cnsideratins) f this manual, include: Cllectin f medical histry, cncmitant medicatins and physical, genital and anrectal exams. Evaluatin f prhibited medicatins/prducts, STI/RTI/UTIs, genital signs/symptms, and verall general health. Participants shuld receive all available test results and treatment r referrals fr treatment fr UTI/RTI/STIs. Details regarding labratry tests and sample cllectin at screening are prvided in Sectin 9 (Labratry Cnsideratins) f this manual. In summary, participants will receive: Testing fr HIV, STIs (GC/CT, HSV, and Syphilis), HBsAg, Cagulatin (PT/INR), Anti-HCV, serum chemistries (creatinine, AST, ALT), and CBC with platelets and differentials. Participants will als be cunseled abut HIV and receive apprpriate pre- and pst-test cunseling as well as risk reductin cunseling. Further infrmatin regarding the generatin and structure f PTIDs fr MTN-033 can be fund in Sectin 12 (Data Cllectin) f this manual. 5.3.3 Screening and Enrllment Lg The DAIDS plicy n Requirements fr Essential Dcuments at Clinical Research Sites Cnducting DAIDS Funded and/r Spnsred Clinical Trials requires study sites t dcument screening and enrllment activity n screening and/r enrllment lgs. Screening and/r enrllment lgs may be maintained separately r cmbined int ne dcument. A sample Screening and Enrllment Lg suitable fr use in MTN-033 is available n the MTN-033 webpage under Study Implementatin Materials. Study sites are encuraged t reference the eligibility cdes listed at the bttm f the sample lg when recrding all reasn(s) fr screening failure/discntinuatin. 5.3.4 Participants Fund t be Ineligible (Screen Failures) Screening prcedures shuld be discntinued when the participant is determined t be ineligible. If a participant screens ut due t a clinical cnditin requiring fllw-up, apprpriate referrals shuld be prvided t ensure the well-being f the participant. Dcumentatin f all referrals shuld be included in the participant chart. All lab results shuld be prvided and explained t participants within a reasnable timeframe, regardless f eligibility determinatin. Fr all screened ut participants, the fllwing dcumentatin shuld be in place: Cmpleted ICF(s) Cmpleted Inclusin/Exclusin CRF Reasn(s) fr ineligibility, with date f determinatin, as per the cmpleted Eligibility Checklist Necessary referrals n file (as apprpriate) and dcumentatin that any clinically significant abnrmalities (labs, etc.) were cmmunicated t the participant (even if referral is nt necessary) All surce dcumentatin cmpleted up until the time that ineligibility was determined including: Chart ntes cmplete up until the time ineligibility was determined Sectin 5 Prtcl Versin 2.0, dated 08 December 2017 Page 5-3
Indicatin f what visit prcedures were cnducted (n visit checklists) Shuld a participant be ineligible fr enrllment, the Eligibility Checklist shuld be cmpleted, including the applicable inclusin and/r exclusin criteria selected, and the screening file shuld be retained n site. In additin, the Screening and Enrllment Lg shuld be updated with the date f discntinuatin f the screening and reasn fr the screen failure. 5.4 Enrllment Visit A participant s final eligibility status shuld be determined after cmpletin and final sign ff n the Eligibility Checklist. The site IR (r designee) and a secnd staff member, per site SOP, shuld sign and date the Eligibility Checklist t affirm/cnfirm eligibility. A participant may nly be enrlled after the final assessment f eligibility is cmpleted. A participant is cnsidered enrlled in the study nly after s/he has been randmized. All baseline samples, assessments, and examinatins must be cllected/cmpleted befre a participant is randmized (the definitin f enrllment). Further infrmatin n randmizatin is prvided in Sectin 12 (Data Cllectin) f this manual. If site staff identify that an ineligible participant has inadvertently been enrlled in the study, the Investigatr f Recrd r designee shuld cntact the MTN-033 Prtcl Safety Review Team (PSRT) and the MTN-033 Management Team fr guidance n subsequent actin t be taken. 5.4.1 Enrllment Visit Prcedures Enrllment/Visit 2 serves as the baseline visit fr MTN-033. All prcedures fr this visit must be cnducted n the same day, and cannt be split acrss multiple days. Further guidance will be prvided n a site-by-site basis. Study enrllment prcedures are specified in prtcl sectin 7.3 and reflected in the visit checklist available n the MTN-033 webpage. The fllwing prcedures will be cmpleted as part f eligibility cnfirmatin prir t randmizatin n the day f enrllment. Befre randmizatin, the fllwing prcedures will be cnducted: Review and update lcatr infrmatin Review infrmed cnsent and cnfirm participant remains interested in cntinued study participatin Cnfirm behaviral eligibility criteria (thrugh administratin f the Enrllment Behaviral Eligibility Wrksheet prvided n the MTN-033 study webpage under Study Implementatin Materials.) Update medical histry since screening visit. Evaluate use f prhibited medicatins, STI/UTIs, genital r reprductive tract signs/symptms, and verall general health. If clinically indicated, cnduct a dipstick UA and/r urine culture. Cllect bld fr: HIV testing and plasma archive. If indicated, als cllect bld fr serum chemistries, CBC with differential and platelets, and syphilis serlgy. In cnjunctin with HIV testing, participants will receive HIV pre- and pst-test cunseling as well as risk reductin cunseling. Cnduct a physical exam Cnduct a genital and anrectal exam t cnfirm eligibility and cllect baseline anrectal samples. Nte: If participant is nt eligible fr enrllment, samples cllected during this exam must be destryed. Participants shuld be tested fr GC/CT and HSV if indicated Participants shuld receive all available test results and treatment r referrals fr STI/UTIs, genital r reprductive tract infectins. Sectin 5 Prtcl Versin 2.0, dated 08 December 2017 Page 5-4
Cmplete the Baseline Behavir CASI Questinnaire Prtcl adherence and study prduct adherence cunseling. Nte: this may als be cnducted after randmizatin, but it culd be helpful t prvide the participant with mre infrmatin abut prduct administratin prir t his/her final decisin t enrll in the study On the day f Enrllment, participants will be assigned t: Time assignment: Participants will be assigned a time pint in which they will prvide rectal fluid and tissue samples at Dsing Visits 3 and 5. During these visits, participants will either prvide samples 1 hur r 4 hurs after study prduct is administered. This assignment will be maintained fr each dsing visit. Gel Applicatin Sequence: Participants will be asked t apply the study gel twice during their time in the study. During enrllment, participants will be tld the rder in which they will use the study prduct applicatin methds at Dsing Visits 3 and 5. At these visits, participants will fllw their assigned rectal gel applicatin methd study sequence and insert the study gel int the rectum using either an applicatr r a cital simulatin device (dild). Prir t the participant leaving the clinic, site staff shuld prvide the participant with site cntact infrmatin and reimbursement, and schedule the participant s next visit. Please nte, n prduct will be administered at the enrllment visit. 5.5 Fllw-up Visits Once a participant is enrlled in the study, the participant will have 5 mre visits/cntacts. It is imprtant t discuss the visit schedule with the participant t ensure that the participant can meet the study expectatins. 5.5.1 Types f Fllw-up Visits Thrughut the study fllw-up perid, tw types f fllw-up visits may be cnducted (scheduled and interim visits): Scheduled visits are thse visits required per prtcl. There are 4 clinic fllw-up visits, fllwed by the Fllw-up cntact/terminatin. Visits 3 and 5 (Dsing Visits): Visit 3 is scheduled apprximately 10 days after Visit 2/Enrllment. Visit 5 ideally shuld ccur 14-28 days after Visit 4/Sampling Visit. Participants will be randmized t prvide samples at either 1 hur r 4 hurs after dse administratin (see sectin 5.4.1 abve). Please nte, there is a +/- 15minute allwable windw arund each f these sampling timepints. Visit 4 (Sampling Visit): Visit 4 shuld ideally ccur ~24 hurs after Dsing Visit 3. Participants will have rectal samples cllected and, if indicated, bld cllected. When scheduling this visit, ensure enugh staff will be available t perfrm visit prcedures. Please nte, there is a +/- 4-hur allwable windw arund this visit. Visit 6 (Sampling Visit): Visit 6 shuld ideally ccur ~24 hurs after Dsing Visit 5. All participants will have bld and rectal samples cllected, s when scheduling this visit, ensure enugh staff will be available t perfrm visit prcedures. Please nte, there is a +/- 4-hur allwable windw arund this visit. NOTE: Between Visit 4 and Visit 5 participants will have a washut perid. The washut perid will be a minimum f 14 days and a maximum f 28 days (see study Visit Windws belw). Sectin 5 Prtcl Versin 2.0, dated 08 December 2017 Page 5-5
Visit 7 (Fllw-up Cntact/Terminatin): This cntact culd be either a clinic visit r a telephne cntact. Early Terminatin Visit: If a participant must be terminated early, the prcedures fr Visit 6 are t be fllwed. NOTE: Further fllw-up visit cnsideratins are described in sectin 5.5.3 belw. Interim visits are thse visits that take place between scheduled visits. All interim cntacts (e.g., phne calls and/r clinic visits) will be prperly dcumented in study files and n applicable data frms. Prcedures required during an interim visit will depend n the reasn fr the visit. See SSP Sectin 12 (Data Cllectin) fr details n interim study visits and visit cdes. 5.5.2 Fllw-up Visit Scheduling Target Visit Dates Each participant s enrllment date is defined as the date upn which the MTN-033 staff member randmizes a participant via Medidata Rave. Staff shuld strive t have the participant cmplete a specified fllw-up visit n the target date fr that visit. Visit Windws Acknwledging that it will nt always be pssible t cmplete fllw-up visits n the targeted dates, the MTN-033 prtcl allws fr visits t be cmpleted within a visit windw. All visits have visit windws specifying which study days the visit can be cmpleted n. A cmplete listing f visit windws is available in Sectin 12 (Data Cllectin) f this manual. The site is encuraged t cmplete required study visits within the visit windw. Visits cmpleted within the visit windw will be cnsidered cmpleted ("retained") visits. Althugh the visit windws allw fr sme flexibility, the intent f the prtcl-specified visit schedule is t cnduct fllw-up visits at specific intervals, and every effrt shuld be made t d s. The MTN Statistical and Data Management Center (SDMC) will prvide the site with a visit calendar tl (als available n the MTN-033 webpage under Study Implementatin Materials) that can be used t create fllw-up visit schedules fr enrlled participants. Every effrt shuld be made t schedule participants within the alltted timeframes. Visits Cnducted Over Multiple Days: Split Visits Ideally, all prcedures specified by the prtcl t be perfrmed at a fllw-up visit will be cmpleted at a single visit n a single day. If all required prcedures cannt be cmpleted n a single day (e.g., because the participant must leave the study site befre all required prcedures are perfrmed), the remaining prcedures may be cmpleted n subsequent day(s) within the allwable visit windw. When this ccurs, the visit is cnsidered a split visit. As described in Sectin 12 (Data Cllectin) f this manual, all frms cmpleted fr a split visit are assigned the same visit cde (even thugh the dates recrded n the frms may be different). Fr study visits requiring cllectin f PK, PD, and mucsal safety samples, please ensure these prcedures are dne n the first day f the split visit t avid cmplicating interpretability. Additinally, if a CASI interview is required, the entire CASI interview must be cmpleted n a single day. If at Visit 3 r 5 the CASI interview is begun but nt cmpleted, the entire CASI questinnaire must be re-administered (starting frm the beginning) at the next visit, in additin t Sectin 5 Prtcl Versin 2.0, dated 08 December 2017 Page 5-6
ther prtcl-specified prcedures fr the applicable visit. If this ccurs, the SDMC and the BRWG shuld be ntified and a new CASI ID shuld be administered fr the CASI; the fully cmpleted CASI questinnaire will be used fr analysis purpses. If all required prcedures cannt be cmpleted n a single day and that visit des nt have a windw, the remaining prcedures are cnsidered missed. Dcumentatin f the ratinale fr nt cmpleting the prcedures shuld be included in the participant s chart. Missed Visits A visit is cnsidered missed if nne f that visit s prcedures are cmpleted within the allwable visit windw. If the visit is missed, a Missed Visit frm must be cmpleted t dcument the missed visit (see the CRF Cmpletin Guidelines fr mre infrmatin n cmpletin f this frm). If Visit 3 r 5 is missed, site staff shuld cnsult the Management Team fr guidance n whether a replacement participant shuld be enrlled. A missed visit in this case is defined as a participant nt cmpleting the visit (e.g., participant des nt present t the clinic fr the visit within the allwable windw, participant has been discntinued frm study prduct use and has been withdrawn frm the study). The purpse f replacing participants is t cmpensate fr the ptential data lss. Replacement decisins will be made n a case by case basis by study leadership and the MTN-033 Management Team. Site staff shuld cmplete the Participant Replacement Assessment frm as sn as a participant meets a criterin fr replacement and has apprval f the Management Team. If Visit 4 r 6 is missed, the participant shuld be requested t return t the clinic as sn as pssible, if willing, t cmplete prtcl-specified prcedures that were missed (please cntact SCHARP as t the cding f this visit): If Visit 4 is missed, participants shuld return t the clinic as sn as pssible t make up the fllwing prcedures: Review/update lcatr infrmatin, medical and medicatin histry and assess fr AEs Prvide prtcl cunseling Cllect bld fr PK Cnduct rectal exam and cllect required PK, PD and mucsal safety samples (rectal fluid, tissue and effluent) If Visit 6 is missed, participants shuld return t the clinic as sn as pssible t make up the fllwing prcedures: Review/update lcatr infrmatin, medical and medicatin histry and assess fr AEs Prvide prtcl cunseling and HIV pre/pst and risk reductin cunseling Cllect bld fr PK, serum chemistries and HIV testing Cnduct rectal exam and cllect required PK, PD and mucsal safety samples (rectal fluid, tissue and effluent) Refer t sectin 5.5.4 belw fr additinal guidance t be fllwed when disclsing available tests results t the participants. Study terminatin can ccur up t 14 days after the last sampling visit 5.5.3 Fllw-up Visit Prcedures Each participant enrlled in the study is expected t cmplete 4 prtcl-required in-clinic visits and ne Fllw-up Cntact/Terminatin visit. Required fllw-up visit prcedures are listed in prtcl sectins 7.4-7.9 and Appendix I. As a general guide, during fllw up, the fllwing will ccur: Lcatr infrmatin must be btained/reviewed at every visit. Prtcl cunseling will be prvided at all visits. Sectin 5 Prtcl Versin 2.0, dated 08 December 2017 Page 5-7
Medical histry, AE assessment and dcumentatin, assessment f cncmitant medicatins, and prvisin f any available lab results, will be dne at all fllw-up study visits. Participants will be reimbursed fr their time at each visit and scheduled fr their next visit as applicable. Cndms will be ffered at all visits. HIV testing and cunseling are required at visits 2 and 6. Chemistries are required nly at visit 6 nly. Targeted physical exam, CBC with differential and platelets, dipstick UA, urine culture, and NAAT fr GC/CT are dne nly if clinically indicated. Per prtcl, n the day f dsing (Visits 3 and 5), bld will be cllected at baseline (prir t gel applicatin and at 0.5, 1, 1.5, 2, 2.5, 3, and 4 hurs after gel applicatin. Depending n randmizatin, rectal samples (fluid and tissue) will be cllected at either 1 r 4 hur(s) after gel applicatin. At sampling visits (Visits 4 and 6), bld and rectal samples (fluid and tissue) shuld be cllected apprximately 24 hurs after gel applicatin. Please reference Sectin 9 (Labratry Cnsideratins) fr additinal infrmatin related t genital specimen and bld cllectin cnsideratins. The table belw shws the allwable windws fr samples cllected pst dse administratin. Visit/Visit Type Sample Schedule Sample Cllectin Windw Visit 3 (Dsing Visit) Visit 5 (Dsing Visit) Bld: baseline (0 hurs/pre-dse) and 0.5, 1, 1.5, 2, 2.5, 3, and 4 hurs after dse Rectal samples: 1 r 4 hurs after dse Bld: baseline (0 hurs/pre-dse), 0.5, 1, 1.5, 2, 2.5, 3, and 4 hurs after dse Rectal samples: 1 r 4 hurs after dse -/+ 15 minutes +/- 30 minutes -/+ 15 minutes +/- 30 minutes Nte: Rectal swab fr PK must be cllected within ne hur f the PK bld draw. Given the 1 and 4- hur rectal samples verlap with the 1 and 4-hur required bld samples, there is a -/+30-minute allwable windw arund the rectal samples. 5.5.4 Visit 7 Cntact/Terminatin Cnsideratins The Visit 7 Cntact/Terminatin visit culd be scheduled as an in-clinic visit r as a phne call. Site staff shuld discuss with the participant what prcedures will be cnducted during this visit/cntact. Depending n the results f labs cllected at Visit 6, r if Visit 6 is missed, a clinic visit may be necessary r a call may suffice. Fr example, staff and participant may have agreed t a phne call, but based n test results r if missed labs need t be made up, it may be necessary fr the participant t present t the clinic t receive study results and cunseling. It is imprtant that staff discuss this with participants during the infrmed cnsent prcess as well as when the participant s fllw up visit schedule is generated. It is als ideal t remind participants during Visit 6 t ensure the participant is agreeable and understand what may be expected after study terminatin. Additinal cntacts als are required fr: Participants with psitive r indeterminate HIV rapid r cnfirmatry test results Sectin 5 Prtcl Versin 2.0, dated 08 December 2017 Page 5-8
Participants with certain types f AEs that are nging at study exit (See detailed guidance in Sectin 8 ((Adverse Event Reprting and Safety Mnitring) f this manual) Fr each participant, a final cntact, which may ccur after Visit 7, shuld be scheduled based n the participant s verall clinical picture at study exit, as well as the time required t btain all final study test results. It is recmmended that final cntact plans be dcumented n chart ntes r a site-specific tl (e.g. wrksheet), but n frms are submitted fr these pst-terminatin cntacts. After cmpleting the Visit 7 Cntact/Terminatin visit and final study cntacts, participants will n lnger have rutine access t services prvided thrugh the study such as HIV cunseling and testing r cndm prvisin. Participants shuld be cunseled abut this ideally befre and during their Visit 7 Cntact/Terminatin visit and prvided infrmatin n where they can access such services after study exit. It is recmmended that all study sites develp written referral sheets that can be given t participants; if the Visit 7 Cntact/Terminatin visit is planned as a phne call, this infrmatin shuld be prvided t the participant prir t Terminatin. If the Visit 7 Cntact/Terminatin visit is planned as an in-clinic visit, this infrmatin culd be prvided t participants at that time. All participants will be cntacted pst-study t be infrmed f the study results. Participant preferences fr methds t be used fr cntacting them when study results are available shuld be dcumented in participant study recrds. Lastly, fr participants whm study staff may wish t cntact regarding participatin in future studies, permissin fr such cntact shuld be sught frm the participant and dcumented. It is recmmended that participant permissin (r lack theref) fr future studies be dcumented n a study exit wrksheet r ther site-specific dcumentatin that can be easily accessed by study staff. 5.5.5 Participants Wh Becme Infected with HIV Per prtcl sectin 9.3, study prduct use must be discntinued immediately fr participants with a reactive HIV test result (this includes participants with discrdant rapid results frm the same visit). If a participant becmes infected with HIV-1 after the Enrllment Visit, s/he will be referred t lcal care and treatment services and may return t the research clinic fr additinal cunseling and ther supprt services, as needed per site SOP. Once HIV status is cnfirmed, study fllw-up visits will be discntinued and the participant will be cnsidered terminated frm the study. Participants wh sercnvert after randmizatin may be ffered additinal labratry testing (such as HIV RNA and HIV drug resistance testing), as clinically indicated per site SOP. 5.5.6 Participants Wh Permanently Discntinue Study Prduct fr Other Reasns Fr participants wh permanently discntinue study prduct use fr any ther clinician initiated reasn (ther than HIV sercnversin) r participant initiated (participant decides t withdraw frm the study r stp using study prduct), will be cnsidered terminated frm the study (see Prtcl Sectin 7.5.2). 5.5.7 Criteria fr Early Terminatin f Study Participants As utlined in Prtcl Sectin 9.5, participants may vluntarily withdraw frm the study fr any reasn at any time. The IR/designee als may withdraw participants frm the study, after cnsultatin with the PSRT, t prtect their safety and/r if they are unwilling r unable t cmply with required study prcedures. Participants als may be withdrawn if NIAID, MTN, gvernment r regulatry authrities, including the FDA and Office fr Human Research Prtectins (OHRP), r site IRBs/ECs terminate the study prir t its planned end date. Sectin 5 Prtcl Versin 2.0, dated 08 December 2017 Page 5-9
If the participant is terminating early frm the study fr any reasn, staff shuld cmplete the fllwing: Ask participant if s/he is willing t cmplete ne last visit, during which the Visit 6 Sampling Visit/Early Terminatin Visit prcedures shuld be cmpleted. Please nte, PK, PD and mucsal safety sample cllectin will be dne at the discretin f the MTN-033 Management Team (see sectin 5.5.1 abve fr additinal guidance). If specimens are cllected, this must ccur within 72 hurs f a previusly received dse and if bipsies were nt cllected fr Visit 4 r 6. Recrd the reasn(s) fr the withdrawal in participants study recrds. Cnsultatin with the PSRT regarding early terminatins per IR decisin shuld be printed and filed in the participant chart. PSRT cnsultatin is nt required fr vluntary withdrawals. Update the participant lcatr frm, and dcument hw the participant wuld like t receive any fllw up test results (as needed), and be infrmed f study results. Once a participant withdraws frm the study, s/he will nt be able t rejin the study. Sectin 5 Prtcl Versin 2.0, dated 08 December 2017 Page 5-10