Conditions: HIV Infections
Keywords: Pre-Exposure Prophylaxis PrEP
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 9
Healthy volunteers: yes

Brief summary:
This study will establish the minimum safety, tolerability and acceptability data needed to support the use of cabotegravir long-acting injection (CAB LA) in an adolescent population, potentially transforming the field of HIV prevention for young people.

Detailed description:
The purpose of this study is to establish the minimum safety, tolerability and acceptability data needed to support the use of cabotegravir long-acting injection (CAB LA) in an adolescent population, potentially transforming the field of HIV prevention for young people.

This study will enroll healthy, HIV-uninfected adolescents assigned male at birth, including men who have sex with men (MSM), transgender women (TGW), and gender non-conforming people. The total participant commitment for the entire study is approximately 1.5 years.

This study will take place in three steps. In Step 1, participants will receive daily oral CAB tablets for 5 weeks. In Step 2, participants will receive a series of five intramuscular (IM) injections of CAB LA, administered at 8-week intervals after a 4-week loading dose (injections at Weeks 5, 9, 17, 25 \& 33). A safety visit will follow each injection to ascertain safety data, including injection site reactions. In Step 3, all participants who have received at least one injection will be followed quarterly (every 3 months) for 48 weeks after their last injection. Participants will receive oral TDF/FTC for daily use for 48 weeks or may be provided the opportunity to enroll in a local open label study of CAB, if available.

Participants will attend about 18 study visits throughout the study. Visits may include physical examinations, blood collection, urine collection, rectal and oral pharyngeal swab collection, risk reduction and adherence counseling, and behavioral or acceptability assessments.

Arms:
arm 1: In Step 1, participants will receive one CAB tablet orally every day for 5 weeks. In Step 2, participants will receive an intramuscular (IM) injection of CAB LA at Weeks 5, 9, 17, 25, and 33. In Step 3, participants will receive a TDF/FTC tablet orally every day for 48 weeks or may be offered the opportunity to join an open label CAB study instead, if such a study is being implemented in their area at the time.

Interventions: intervention 1: Cabotegravir (CAB) tablet intervention 2: CAB LA intervention 3: Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) tablet
Intervention descriptions: intervention 1: 30 mg tablets intervention 2: Administered as one 3 mL (600 mg) IM injection in the gluteal muscle at two time points 4 weeks apart and every 8 weeks thereafter. intervention 3: 300 mg/200 mg fixed-dose combination tablets

Protocol document:
Prot_ICF_000.pdf: 
HPTN 083-01, FINAL V3.0 
1 of 152 
2 July 2021 
HPTN 083-01: 
Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the 
Prevention of HIV among Adolescent Males – A sub-study of HPTN 083 
 
 
DAIDS Document ID: 38654 
 
A Study by the HIV Prevention Trials Network (HPTN) 
 
Sponsored by: 
Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious 
Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human 
Development (NICHD), 
US National Institutes of Health (NIH) 
 
Support Provided by: 
ViiV Healthcare 
 
 
 
 
IND Holder: 
DAIDS, NIAID, NIH 
 
IND #: 122,744 
 
Protocol Chair: 
Sybil Hosek, PhD 
 
Protocol Co-Chair: 
Lynda Stranix-Chibanda, MBChB, MMED 
 
 
FINAL Version 3.0 
 
2 July 2021 
 
 
 


HPTN 083-01, FINAL V3.0 
2 of 152 
2 July 2021 
HPTN 083-01: 
Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the 
Prevention of HIV among Adolescent Males – A sub-study of HPTN 083 
 
TABLE OF CONTENTS 
 
LIST OF ABBREVIATIONS AND ACRONYMS .....................................................................6 
PROTOCOL TEAM ROSTER ..................................................................................................10 
PROTOCOL SIGNATURE PAGE ............................................................................................14 
SCHEMA ......................................................................................................................................15 
1.0 
INTRODUCTION............................................................................................................16 
1.1 Background and Rationale .................................................................................................16 
1.2 Overview of Oral CAB and CAB LA ................................................................................18 
1.3 Metabolism ........................................................................................................................19 
1.4 Preclinical Studies ..............................................................................................................19 
1.5 Dose Rationale ...................................................................................................................20 
1.6 Genital Tract (GT) Tissue Levels after Oral and Injectable Administration .....................22 
1.7 Pediatric Dosing .................................................................................................................22 
1.8 Hepatic and Central Nervous System Adverse Events ......................................................27 
1.9 Weight gain ........................................................................................................................28 
1.10 Rationale for use of Oral Run-in Prior to Injectable Dosing .............................................29 
2.0 
STUDY OBJECTIVES AND DESIGN ..........................................................................29 
2.1 Primary Objectives.............................................................................................................29 
2.2 Secondary Objectives.........................................................................................................29 
2.3 Study Design and Overview ..............................................................................................29 
3.0 
STUDY POPULATION ..................................................................................................30 
3.1 Inclusion Criteria ...............................................................................................................31 
3.2 Exclusion Criteria ..............................................................................................................32 
3.3 Recruitment Process...........................................................................................................33 
3.4 Co-Enrollment Guidelines .................................................................................................33 
3.5 Participant Retention ..........................................................................................................34 
3.6 Participant Withdrawal ......................................................................................................34 
4.0 
STUDY PRODUCT CONSIDERATIONS ....................................................................35 
4.1 Study Product Regimens/Administration/Formulation Content ........................................35 
4.2 Study Product Acquisition and Accountability..................................................................38 
4.3 Toxicity Management ........................................................................................................38 
4.4 Concomitant, Prohibited, and Precautionary Medications ................................................38 
5.0 
STUDY PROCEDURES .................................................................................................40 


HPTN 083-01, FINAL V3.0 
3 of 152 
2 July 2021 
5.1 Screening............................................................................................................................40 
5.2 Enrollment..........................................................................................................................41 
5.3 Step 1, Oral Run-in Phase: Safety Visits ...........................................................................42 
5.4 Transitioning from Step 1 to Step 2 ...................................................................................43 
5.5 Step 2, Injection Phase: Injection Visits ............................................................................44 
5.6 Step 2, Injection Phase: Safety Visits ................................................................................44 
5.7 Step 3, Follow-up Phase ....................................................................................................44 
5.8 Standard of Care (SOC) Counseling for all Participants ...................................................45 
5.9 Injection Visit Windows ....................................................................................................45 
5.10 Procedures for Injectable Dosing .......................................................................................45 
5.11 Participants with Suspected or Confirmed HIV Infection at Screening, Enrollment,    or 
Follow-Up ........................................................................................................................46 
5.12 STIs 47 
5.13 HBV and HCV ...................................................................................................................47 
5.14 Behavioral and Acceptability Assessments .......................................................................48 
5.15 Interim Contacts and Visits ................................................................................................48 
5.16 Criteria for Early Termination of Study Participation .......................................................48 
6.0 
SAFETY MONITORING AND AE REPORTING ......................................................48 
6.1 AE Definition and Reporting .............................................................................................48 
6.2 EAE Reporting ...................................................................................................................49 
6.3 Safety Monitoring ..............................................................................................................50 
6.4 Clinical Data Review .........................................................................................................52 
6.5 Social Harms and Social Benefits Reporting .....................................................................52 
7.0 
STATISTICAL CONSIDERATIONS ...........................................................................52 
7.1 Review of Study Design ....................................................................................................52 
7.2 Endpoints ...........................................................................................................................53 
7.3 Sample Size ........................................................................................................................54 
7.4 Randomization ...................................................................................................................54 
7.5 Blinding..............................................................................................................................54 
7.6 Data and Safety Monitoring Analysis ................................................................................54 
7.7 Primary Analyses ...............................................................................................................55 
7.8 Secondary Analyses ...........................................................................................................57 
7.9 Qualitative Analysis ...........................................................................................................57 
8.0 
HUMAN SUBJECTS CONSIDERATIONS .................................................................58 
8.1 Ethical Review ...................................................................................................................58 
8.2 Informed Consent...............................................................................................................58 
8.3 Incentives ...........................................................................................................................60 
8.4 Confidentiality ...................................................................................................................60 
8.5 Communicable Disease and Statutory Rape Reporting Requirements ..............................60 
8.6 Study Discontinuation ........................................................................................................60 
9.0 
LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT ...................60 


HPTN 083-01, FINAL V3.0 
4 of 152 
2 July 2021 
9.1 Local Laboratory Specimens .............................................................................................61 
9.2 Stored Specimens ...............................................................................................................61 
9.3 Virology .............................................................................................................................62 
9.4 Pharmacology ....................................................................................................................62 
9.5 Quality Control and Quality Assurance Procedures ..........................................................63 
9.6 QC for HIV Diagnostic Testing .........................................................................................63 
9.7 Quality Assurance for General Laboratory Testing ...........................................................63 
9.8 Quality Assurance for CD4 Cell Count Testing ................................................................63 
9.9 Quality Assurance for HIV RNA Testing ..........................................................................63 
9.10 Specimen Storage and Possible Future Research Testing .................................................63 
9.11 Biohazard Containment .....................................................................................................64 
10.0 
ADMINISTRATIVE PROCEDURES ...........................................................................64 
10.1 Protocol Registration .........................................................................................................64 
10.2 Study Activation ................................................................................................................64 
10.3 Study Coordination ............................................................................................................65 
10.4 Study Monitoring ...............................................................................................................65 
10.5 Protocol Compliance ..........................................................................................................66 
10.6 Investigator's Records ........................................................................................................66 
10.7 Use of Information and Publications .................................................................................67 
11.0 
REFERENCES .................................................................................................................68 
12.0 
APPENDICES I – XVI ....................................................................................................71 


HPTN 083-01, FINAL V3.0 
5 of 152 
2 July 2021 
12.1 APPENDIX I. SCHEDULE OF EVALUATIONS – ORAL PHASE (STEP 1) ...............72 
12.2 APPENDIX II. SCHEDULE OF EVALUATIONS – INJECTION PHASE (STEP 2) ....74 
12.3 APPENDIX III. SCHEDULE OF EVALUATIONS –FOLLOW-UP PHASE (STEP 3-
ORAL PrEP) ....................................................................................................................76 
12.4 APPENDIX IV. SCHEDULE OF EVALUATIONS – FOLLOW-UP PHASE (STEP 3-
INJECTION) ....................................................................................................................78 
12.5 APPENDIX V: SCHEDULE OF ADDITIONAL PROCEDURES FOR 
REACTIVE/POSITIVE HIV TESTS ..............................................................................80 
12.6 APPENDIX VI: TOXICITY MANAGEMENT ................................................................82 
12.7 APPENDIX VII: INFORMED CONSENT FOR PARENTS/LEGAL GUARDIANS 
AND ASSENT FOR ADOLESCENT PARTICIPANTS AGES 14 – AGE OF 
MAJORITY ......................................................................................................................92 
12.8 APPENDIX VIII: INFORMED CONSENT FOR ADOLESCENT PARTICIPANTS 
ABLE TO CONSENT FOR THEMSELVES (SELF-CONSENT) AND 
PARTICIPANTS WHO REACH THE AGE OF MAJORITY .....................................106 
12.9 APPENDIX IX: INFORMATION SHEET AND ASSENT FOR ADOLESCENT 
PARTICIPANTS AGES 10-13 ......................................................................................120 
12.10 APPENDIX X: INFORMED CONSENT FOR ADOLESCENT INTERVIEW FOR 
PARENTS/LEGAL GUARDIANS AND ASSENT FOR ADOLESCENT 
PARTICIPANTS AGES 14 – AGE OF MAJORITY ....................................................124 
12.11 APPENDIX XI: INFORMED CONSENT FOR ADOLESCENT INTERVIEW FOR 
ADOLESCENT PARTICIPANTS ABLE TO CONSENT FOR THEMSELVES (SELF-
CONSENT) AND PARTICIPANTS WHO REACH THE AGE OF MAJORITY .......129 
12.12 APPENDIX XII: INFORMATION SHEET AND ASSENT FOR ADOLESCENT 
INTERVIEWS FOR PARTICIPANTS AGES 10-13 ....................................................134 
12.13 APPENDIX XIII: INFORMED CONSENT PARENT/GUARDIAN INTERVIEW FOR 
PARENTS/LEGAL GUARDIANS ...............................................................................136 
12.14 APPENDIX XIV: INFORMED CONSENT FOR SPECIMEN STORAGE AND 
FUTURE USE FOR PARENTS/LEGAL GUARDIANS AND ASSENT FOR 
ADOLESCENT PARTICIPANTS AGES 14 – AGE OF MAJORITY ........................141 
12.15 APPENDIX XV: INFORMED CONSENT FOR SPECIMEN STORAGE AND 
FUTURE USE FOR ADOLESCENT PARTICIPANTS ABLE TO CONSENT FOR 
THEMSELVES (SELF-CONSENT) AND PARTICIPANTS WHO REACH THE AGE 
OF MAJORITY..............................................................................................................146 
12.16 APPENDIX XVI: INFORMATION SHEET AND ASSENT FOR SPECIMEN 
STORAGE AND FUTURE USE FOR PARTICIPANTS AGES 10-13 .......................151 
 
 
 
 


HPTN 083-01, FINAL V3.0 
6 of 152 
2 July 2021 
HPTN 083-01: 
Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the 
Prevention of HIV among Adolescent Males – A sub-study of HPTN 083 
 
LIST OF ABBREVIATIONS AND ACRONYMS 
 
ABC/3TC 
abacavir/lamivudine 
AE 
adverse event 
AIDS 
acquired immunodeficiency syndrome 
ALT 
alanine aminotransferase 
ART 
antiretroviral therapy 
ARV 
Antiretroviral 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
BCRP 
breast cancer resistance protein 
hCG 
beta human chorionic gonadotropin 
BMI 
body mass index 
BUN 
blood urea nitrogen 
C 
Celsius 
C 
trough concentration 
CAB 
cabotegravir, oral and LA formulations 
CAB LA 
long-acting injectable formulation of cabotegravir 
CABG 
CASI 
coronary artery bypass grafting 
computer-assisted self-interview 
CBC 
complete blood count 
CD4 
T-helper cells or T4 cells 
CDC 
(US) Centers for Disease Control and Prevention 
CFR 
(US) Code of Federal Regulations 
CI 
confidence interval 
CLIA 
Clinical Laboratory Improvement Amendments 
Cmax 
maximum or “peak” concentration of a drug observed after its 
administration 
CMC 
Clinical Management Committee 
Cmin 
minimum or “trough” concentration of a drug observed after its 
administration and just prior to the administration of a subsequent dose 
CPQA 
Clinical Pharmacology Quality Assurance Committee 
CPK 
creatine phosphokinase 
CRF 
case report form 
CRM 
Clinical Research Manager 
CRPMC 
Clinical Research Products Management Center 
CRS 
Clinical Research Site 
CT 
Chlamydia trachomatis 
CVb% 
geometric mean 
DAERS 
DAIDS Adverse Event Reporting System 
DAIDS 
Division of AIDS 
DAIDS PRO 
DAIDS Protocol Registration Office 
DAIDS RSC 
DAIDS Regulatory Support Center 
DBS 
dried blood spot 
DMPA 
depot medroxyprogesterone acetate 
DSMB 
Data and Safety Monitoring Board 


HPTN 083-01, FINAL V3.0 
7 of 152 
2 July 2021 
EAE 
expedited adverse event 
EC 
Ethics Committee 
ECLAIR 
Phase IIa Safety and PK Study of Cabotegravir LA in HIV-Uninfected 
Men at Low Risk for Sexual Acquisition of HIV Infection 
EFD 
early fetal development 
EFV 
Efavirenz 
EQA 
external quality assurance 
FDA 
(US) Food and Drug Administration 
FEM-PrEP 
Pre-exposure Prophylaxis Trial for HIV Prevention among African 
Women 
FTC 
Emtricitabine 
FTC-TP 
emtricitabine triphosphate 
GC 
GCLP 
Neisseria gonorrhoeae 
Good clinical laboratory practice 
GT 
genital tract 
HBcAb 
hepatitis B virus core antibody 
HBsAb 
hepatitis B virus surface antibody 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCAb 
HCV 
hepatitis C antibody 
hepatitis C virus 
HDL 
high-density lipoprotein 
HDPE 
high density polyethylene 
HIV 
human immunodeficiency virus 
HIV RNA 
HIV test using a ribonucleic acid 
HIV-1 
human immunodeficiency virus type 1 
HPTN 
HIV Prevention Trials Network 
HPTN LC 
(HPTN) Laboratory Center 
HPTN LDMS 
(HPTN) Laboratory Data Management System 
HPTN LOC 
(HPTN) Leadership and Operations Center 
HPTN SDMC 
(HPTN) Statistical and Data Management Center 
HR 
hazard ratio 
IATA 
International Air Transport Association 
IB 
Investigator Brochure 
ICF 
informed consent form 
ID 
IDI 
Identification 
In-depth interview 
IM 
IMPAACT 
Intramuscular 
International Maternal Pediatric Adolescent AIDS Clinical Trials Network 
IND 
investigational new drug 
INSTI 
integrase strand transfer inhibitor  
IoR 
Investigator of Record  
IP 
Intraperitoneal 
iPrEX OLE 
iPrEx Open Label Extension 
IQA 
(DAIDS) Immunology Quality Assurance 
IRB 
Institutional Review Board 
ISR 
injection site reaction 
IUD 
intrauterine device 
IUS 
Intrauterine system 
LA 
long-acting (injectable) 


HPTN 083-01, FINAL V3.0 
8 of 152 
2 July 2021 
LC 
(HPTN) laboratory center 
LATTE 
Cabotegravir plus Rilpivirine, once a day, after Induction with 
Cabotegravir plus Nucleoside Reverse Transcriptase Inhibitors in 
Antiretroviral-naïve Adults with HIV-1 Infection 
LATTE-2 
Cabotegravir plus Rilpivirine as Long-Acting Maintenance Therapy 
LDL 
low-density lipoprotein 
LDMS 
(HPTN) Laboratory Data and Management System 
LFTs 
LLQ 
liver function tests 
Lower limit of quantification 
LOC 
MedDRA 
MO 
(HPTN) Leadership and Operations Center 
Medical Dictionary for Regulatory Activities 
Medical Officer 
MOP 
Manual of Operations 
MRC 
MRI 
(HPTN) Manuscript Review Committee 
Magnetic resonance imaging 
MSM 
men who have sex with men 
NAAT 
nucleic acid amplification test 
NET-EN 
Norethisterone enanthate 
NI 
non-inferiority 
NIAID 
NICHD 
 
NIH 
(US) National Institute of Allergy and Infectious Diseases 
Eunice Kennedy Shriver National Institute of Child Health and Human 
Development 
(US) National Institutes of Health 
NNRTI 
non-nucleoside reverse transcriptase inhibitor 
NOAEL 
no observed adverse effect level 
NRTI 
nucleotide reverse transcriptase inhibitor 
OHRP 
Office for Human Research Protections 
Oral CAB 
oral formulation of cabotegravir 
PA-IC90 
protein-adjusted 90% inhibitory concentration 
PAL 
PBMC 
PEP 
Pgp 
Protocol Analyte List 
Peripheral blood mononuclear cells 
Post-exposure prophylaxis 
Permeability glycoprotein 
PHQ-9 
PI 
Patient Health Questionnaire-9 
package insert 
PK 
Pharmacokinetic 
PO 
by mouth/orally 
PPN 
pre- and postnatal development 
PrEP 
pre-exposure prophylaxis 
PROUD 
Pre-exposure Prophylaxis to Prevent Acquisition of HIV-1 Infection 
pSMILE 
Patient Safety Monitoring and International Laboratory Evaluation 
PSRC 
(DAIDS) Prevention Science Review Committee 
PTCA 
percutaneous transluminal coronary angioplasty 
PY 
person-years 
QA 
quality assurance 
QC 
quality control 
QT 
time between the start of the Q wave and the end of the T wave 
RCT 
randomized clinical trial 
RE 
regulatory entity 
RNA 
ribonucleic acid 


HPTN 083-01, FINAL V3.0 
9 of 152 
2 July 2021 
RPV 
Rilpivirine 
RPV LA 
rilpivirine long-acting (injectable) 
SAE 
serious adverse events 
SC 
Subcutaneous 
SDMC 
(HPTN) Statistics and Data Management Center 
SHIV 
simian human immunodeficiency virus 
SMC 
SMS 
Study Monitoring Committee 
Short message service 
SOC 
standard of care 
SOE 
Schedule of evaluations 
SOP 
standard operating procedure 
SSA 
sub-Saharan Africa 
SSP 
Study Specific Procedures Manual 
SRC 
(HPTN) Scientific Review Committee 
STI 
sexually transmitted infection 
TBili 
total bilirubin 
TCID 
tissue culture infective dose 
TDF 
tenofovir disoproxil fumarate 
TDF/FTC 
tenofovir/emtricitabine (trade name: TDF/FTC, Truvada®) 
TFV 
Tenofovir 
TFV-DP 
tenofovir diphosphate 
TGW 
Tmax 
transgender women 
time after drug administration when maximum drug concentration in 
serum is reached 
TP 
Triphosphate 
TV 
UGT 1A1 
UKNEQAS 
Trichomonis vaginalis 
Uridine diphosphate glucuronyltransferase type 1A1 
United Kingdom National External Quality Assessment Service 
ULN 
upper limit of normal 
US 
United States of America 
VOICE 
Vaginal and Oral Interventions to Control the Epidemic 
VQA 
(DAIDS) Virology Quality Assurance 
WHO 
YKPs 
YMSM 
World Health Organization 
Youth key populations 
Young men who have sex with men 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


HPTN 083-01, FINAL V3.0 
10 of 152 
2 July 2021 
HPTN 083-01: 
Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the 
Prevention of HIV among Adolescent Males – A sub-study of HPTN 083 
 
PROTOCOL TEAM ROSTER 
 
 
PROTOCOL CHAIR: 
Sybil Hosek, PhD 
Clinical Psychologist/Director of Research 
Department of Psychiatry 
Stroger Hospital of Cook County 
1900 W Polk Street, #854 
Chicago, IL 60612 
United States 
Phone: +001 312 864 8030 
Fax: +001 312 864 9203 
Email: shosek@cookcountyhhs.org 
 
PROTOCOL CO-CHAIR: 
Lynda Stranix-Chibanda, MBChB, MMED 
University of Zimbabwe 
Faculty of Medicine and Health Sciences 
Department of Primary Health Care Sciences 
Child and Adolescent Health Unit 
Harare 
Zimbabwe 
Phone: +263 24 2704890 
Fax: +263 24 2704897 
Email: lstranix@uzchs-ctrc.org 
 
Adeola Adeyeye, MD, MPA 
Medical Officer 
Prevention Science Program 
DAIDS, NIAID, NIH 
Room 8B36 MSC 9831 
5601 Fishers Lane  
Rockville, MD 20852-9831 
United States 
Phone: +001 240 669 5005  
Cell: +001 240 619 9365 
Email: adeola.adeyeye@nih.gov  
   
Bill G. Kapogiannis, MD  
Eunice Kennedy Shriver National Institute of 
Child Health and Human Development 
(NICHD) 
BG 6710B RM 2150 
6710B Rockledge Dr. 
Bethesda, MD 20817  
United States 
Phone: +001 301 402 0698 
Fax: +001 301 480 3882 
Email: bill.kapogiannis@nih.gov 
Erica Hamilton, MPH 
HPTN LOC 
Senior Clinical Research Manager  
FHI 360 
359 Blackwell Street, Suite 200 
Durham, NC 27701 
United States 
Phone: +001 919 544 7040, Ext. 11295 
Email: ehamilton@fhi360.org 
Scott Rose, BS 
HPTN LOC  
Clinical Research Project Manager  
FHI 360 
359 Blackwell Street, Suite 200 
Durham, NC 27701 
United States 
Phone: +001 919 544 7040, Ext. 11378 
Email: srose@fhi360.org 
  
 
 


HPTN 083-01, FINAL V3.0 
11 of 152 
2 July 2021 
Katherine Shin, PharmD 
Sr. Pharmacist 
Pharmaceutical Affairs Branch 
Division of AIDS/NIAID/NIH 
5601 Fishers Lane, Room 9D30, MSC 9829 
Rockville, MD 20852 
Phone: +001 240- 627- 3047 
Fax: +001 301-402-1506 
Email: KaShin@niaid.nih.gov 
Lynda Emel, PhD 
HPTN SDMC Associate Director 
SCHARP-FHCRC  
1100 Fairview Avenue N, M2-C200  
PO Box 19024 
Seattle, WA 98109 
United States 
Phone: +001 206 667 5803 
Fax: +001 206 667 4812 
Email: lemel@scharp.org    
 
Mark Marzinke, PhD, DABCC 
Analytical Pharmacologist 
HPTN Laboratory Center 
Johns Hopkins University  
Department of Pathology  
1800 Orleans Street 
Sheikh Zayed Tower, Room B1-1020F 
Baltimore, MD 21287  
United States 
Phone: +001 443 287 7516 
CPAL Office: +001 410 550 9702 
Email:  mmarzin1@jhmi.edu 
 
Lisa Hightow-Weidman, MD, MPH 
Institute for Global Health and Infectious 
Diseases 
University of North Carolina at Chapel Hill 
130 Mason Farm Road, CB#215 
Chapel Hill, NC 27599 
United States 
Phone: +001 919 843 0033 
Email: lisa_hightow@med.unc.edu 
 
Alex Rinehart, PhD 
ViiV Healthcare 
5 Moore Drive 
Durham, NC 27709 
United States 
Phone:  +001 919 483 2085 (office) 
Phone: +001 919 599 7551 (mobile) 
Email: alex.r.rinehart@viivhealthcare.com 
 
Cindy McCoig, MD 
ViiV Healthcare 
Severo Ochoa, 2 
28760 Tres Cantos  
Madrid 
Spain 
Phone: +34 608 831 611 
Email: cynthia.c.mccoig@viivhealthcare.com   
Nirupama Sista, PhD 
HPTN LOC Director 
FHI 360 
359 Blackwell Street, Suite 200 
Durham, NC 27701 
United States  
Phone: +001 202 884 8353 
Fax: +001 202 884 8400 
Email: nsista@fhi360.org 
Linda-Gail Bekker, MBChB, DTMH, DCH, 
FCP 
Desmond Tutu HIV Centre 
Institute of Infectious Disease & Molecular 
Medicine 
University of Cape Town Faculty of Health 
Sciences 
Cape Town, 7925 
South Africa 
Phone: +27 021 6506970 
Fax: +27 021 6506959 
Email: Linda-Gail.Bekker@hiv-
research.org.za 
 
Tim Skalland, PhD  
HPTN SDMC  
SCHARP-FHCRC  
Brett Hanscom, PhD  
HPTN SDMC  
SCHARP-FHCRC  


HPTN 083-01, FINAL V3.0 
12 of 152 
2 July 2021 
1100 Fairview Avenue N 
PO Box 19024  
Mail Stop: M2-C200 
Seattle, WA 98109  
United States 
Phone: +001 206 667 1186  
Email: tskallan@fredhutch.org 
   
1100 Fairview Avenue N 
PO Box 19024  
Seattle, WA 98109  
United States 
Phone: +001 206 667 4534  
Email: bhanscom@fredhutch.org  
 
 
Sinead Delany-Moretlwe, MBBCh, PhD, 
DTM&H 
Wits Reproductive Health and HIV Institute 
CRS (WRHI CRS) 
University of the Witwatersrand 
Hillbrow Health Precinct, 22 Esselen Street 
Johannesburg, 2001 
South Africa 
Phone:  +27 11 358 5414 
Fax:  +27 86 426 5575 
Email: sdelany@wrhi.ac.za 
 
Raphael J. Landovitz, MD, MSc 
UCLA Center for Clinical AIDS Research & 
Education 
11075 Santa Monica Blvd, Suite 100 
Los Angeles, CA 90025 
Phone: +001 310 825 3782  
Fax: +001 310 477 7657  
Email: rlandovitz@mednet.ucla.edu 
 
 
Philip Sullivan, MPH, MLS (ASCP)CM 
HPTN Laboratory Center  
Johns Hopkins University 
Department of Pathology 
600 North Wolfe Street, Pathology 311 
Baltimore, MD 21287 
United States 
Phone: +001 410 502 5720 
Email: psulli22@jhmi.edu 
Ethel D. Weld, MD 
HPTN Laboratory Center 
Johns Hopkins University  
Division of Clinical Pharmacology 
600 North Wolfe Street, Osler 508 
Baltimore, MD 21287 
United States 
Phone: +001 410 502 8129 
Fax: +001 410 955 9708    
Email: eweld@jhmi.edu 
 
Kathleen M. MacQueen, PhD, MPH 
Senior Social Scientist 
Behavioral, Epidemiological & Clinical 
Sciences 
FHI 360 
359 Blackwell Street, Suite 200 
Durham, NC  27701 USA  
Phone: +001 919 544 7040, Ext. 11587  
Fax: +001 919 544 7261 
Email: kmacqueen@fhi360.org  
 
Paul Richardson, MSc 
HPTN Laboratory Center Senior QA/QC 
Coordinator 
Johns Hopkins University 
Department of Pathology 
600 North Wolfe Street, Pathology 306 
Baltimore, MD 21287 
United States 
Phone: +001 410 502 0435 
Email: pricha18@jhmi.edu 
Amber Babinec HPTN LOC 
Prevention Research Specialist FHI 360 
359 Blackwell Street, Suite 200 
Durham, NC 27701 
United States 
Email: ababinec@fhi360.org  
 
Jontraye Davis, MHA 
Community Programs Associate II  
Science Facilitation, FHI 360 
359 Blackwell Street, Suite 200 
Durham, NC 27701 
United States 
Phone: +001 919 544 7040, Ext. 11715 
Email: jodavis@fhi360.org 


HPTN 083-01, FINAL V3.0 
13 of 152 
2 July 2021 
 
Julie Ngo, MPH 
HPTN SDMC Clinical Data Manager 
SCHARP-FHCRC 
1100 Fairview Avenue N 
PO Box 19024 
Seattle, WA 98109 
United States 
Phone: +001 206 667 2094 
Email: jhngo@scharp.org 
 
Jean Paul Pease 
HPTN SDMC Clinical Data Manager 
SCHARP-FHCRC 
1100 Fairview Avenue N 
PO Box 19024 
Seattle, WA 98109 
United States 
Phone: +001 206 667 2793 
Email: jpease@scharp.org 
Aundria Charles, RN, BSN, CCRP 
Senior Clinical Research Associate 
WESTAT-1600 Research Blvd. 
Rockville, MD 
Office Phone: +001 240 453 2758 
Email: AundriaCharles@westat.com 
 
 
Molly Dyer 
Community Programs Associate  
FHI 360 
359 Blackwell Street, Suite 200 
Durham, NC 27701 
United States 
Email: mdyer@fhi360.org 
 
 
 
 
 


 
HPTN 083-01, FINAL V3.0 
14 of 152 
2 July 2021 
HPTN 083-01: 
Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the Prevention 
of HIV among Adolescent Males - A sub-study of HPTN 083 
 
Protocol Signature Page 
 
Version 3.0  
2 July 2021 
 
DAIDS Document ID: 38654 
 
A Study of the HIV Prevention Trials Network (HPTN) 
 
Sponsored by: 
Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases 
(NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human Development 
(NICHD), 
US National Institutes of Health (NIH) 
 
Support Provided by: 
ViiV Healthcare 
 
I will conduct the study in accordance with the provisions of this protocol and all applicable protocol-
related documents. I agree to conduct this study in compliance with United States (US) Health and 
Human Service regulations (45 CFR 46); applicable U.S. Food and Drug Administration regulations; 
standards of the International Conference on Harmonization Guideline for Good Clinical Practice (E6); 
Institutional Review Board/Ethics Committee determinations; all applicable in-country, state, and local 
laws and regulations; and other applicable requirements (e.g., US National Institutes of Health, Division 
of AIDS) and institutional policies. 
 
I have read and understand the information in this protocol and will ensure that all associates, 
colleagues, and employees assisting in the conduct of the study are informed about the obligations 
incurred by their contribution to the study.  
 
 
 
________________________________ 
 
 
Name of Investigator of Record (print name) 
        
 
__________________________________  
____________________ 
 
Signature of Investigator of Record  
 
  
Date (DD/MMM/YYYY) 
 


 
HPTN 083-01, FINAL V3.0 
15 of 152 
2 July 2021 
HPTN 083-01: 
Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the Prevention 
of HIV among Adolescent Males - A sub-study of HPTN 083 
 
SCHEMA 
 
Purpose:  
To establish the minimum safety, tolerability and acceptability data needed to support the use of 
cabotegravir long-acting injection (CAB LA) in an adolescent population, potentially transforming the 
field of HIV prevention for young people. 
  
 
Design:  
A Phase IIB single arm, open label safety, tolerability, and acceptability study. 
 
Population:   
Sexually-active, healthy male (assigned at birth) adolescents aged below 18 years.  
 
Study Size:    
Approximately 50.  
 
Study Duration:  
Participant recruitment will take approximately 18 months. Oral study product will be administered for 5 
weeks, followed by 29 weeks on injectable product, then visits for 48 weeks per Appendix III or IV. All 
participants who have received at least one injection will be followed for 48 weeks after their last 
injection. Waning levels of cabotegravir (the PK tail) will be covered with continued CAB LA or locally 
sourced oral TDF/FTC for daily use for 48 weeks. Total study duration per participant will be 
approximately 21 months. 
 
Study Sites:  
 
 
 
Adolescent and Young Adult Research at The CORE Center (AYAR at CORE), Chicago, IL; St. Jude 
Children’s Research Hospital CRS, Memphis, TN; Fenway Health CRS, Boston, MA; Children’s 
Hospital Colorado CRS, Aurora, CO 
 
Study Regimen:  
Step 1 – oral cabotegravir (30mg tablet); Step 2 – 3 mL (600 mg) intramuscular (IM) CAB LA injection; 
Step 3 – continued 3 mL (600 mg) intramuscular (IM) CAB LA injection or Tenofovir/Emtricitabine 
(Trade name: TDF/FTC, Truvada®) (300mg/200mg tablet)  
 
Primary Objectives:  
• To evaluate the safety, tolerability and acceptability of CAB LA in healthy HIV-uninfected 
male adolescents aged below 18 years. 
Secondary Objectives: 
• To examine adherence to and timeliness of injections over time among adolescent 
participants who are provided CAB LA and information regarding its safety and unknown 
efficacy. 


 
HPTN 083-01, FINAL V3.0 
16 of 152 
2 July 2021 
• To examine patterns of sexual risk behavior over time among adolescent participants who are 
provided CAB LA and information regarding its safety and unknown efficacy. 
• To evaluate the safety of CAB LA for 48 weeks of follow-up after final injection. 
• To characterize the pharmacokinetics of CAB LA 
 
1.0 
INTRODUCTION 
1.1 Background and Rationale 
The burden of HIV infection worldwide is disproportionately borne by youth. 
Despite reductions in other age groups, the number of deaths attributable to HIV is rising in the 
adolescent age group, with AIDS being the leading cause of death among adolescents in Africa and the 
second leading cause for adolescents worldwide.1 Between 2005 and 2012, the number of AIDS-related 
deaths decreased by 30% for all ages except adolescents, who experienced a 50% increase in that same 
period. Similarly, two-thirds of new HIV infections in 2012 occurred among adolescents and young 
adults aged 15 to 24.2 Among youth, there are also key populations that bear disproportionate burdens of 
HIV and are the most vulnerable. These key populations (YKPs) include young men who have sex with 
men (YMSM) globally and adolescent/young adult women in Sub-Saharan Africa.3  
Among YMSM, HIV incidence has been shown to be very high across multiple countries, and global 
reports estimate an HIV prevalence of 4.2% for young gay men under the age of 25.3,4 In the United 
States (US), MSM account for most (72%) new HIV infections among youth aged 13 to 24, making 
them the only group that has shown a significant increase in estimated new infections.5 Young MSM 
who engage in sex work are even more vulnerable to HIV and a study in Kenya found a baseline HIV 
prevalence of 40% among young MSM who sell sex in Nairobi.6 Recent PrEP demonstration studies 
conducted by this investigative team (ATN 110/113) found an HIV incidence of 3.41/100 person-years 
among YMSM ages 18-22 and a staggering 6.41/100 person-years among 15-17 year old participants in 
the US.7,8 
HIV prevention and decreasing HIV-related deaths depend critically on reaching adolescents, engaging 
them in HIV prevention research, and insuring access to HIV prevention products, such as CAB LA, via 
regulatory approvals. Therefore, participants in this trial may directly benefit from taking part in this 
study, HPTN 083-01. 
Oral Pre-exposure Prophylaxis is highly efficacious against HIV, but poor adherence has limited its 
effectiveness for youth.  
Tenofovir-based regimens have been shown to significantly reduce HIV acquisition among men who 
have sex with men (MSM), heterosexual men and women, injection drug users and HIV sero-discordant 
couples.9-12 Given the growing body of evidence about its effectiveness, including encouraging “real 
world” demonstration projects13,14 oral daily PrEP is now recommended for HIV prevention by the US 
Centers for Disease Control and Prevention (CDC), the World Health Organization (WHO) and a 
growing number of countries worldwide.15,16 


 
HPTN 083-01, FINAL V3.0 
17 of 152 
2 July 2021 
As with many daily medication regimens, the effectiveness of oral PrEP is highly dependent on 
adherence to the prescribed drugs. This appears to be particularly true for adolescents and young adults. 
Among MSM, young age has consistently correlated with lower adherence to PrEP. In the iPrEx 
licensing randomized clinical trial9, overall efficacy was 44% for Tenofovir/Emtricitabine (Trade name: 
TDF/FTC, Truvada®) compared with placebo among 2499 MSM, with efficacy increasing to over 90% 
when drug in plasma or peripheral blood mononuclear cells (PBMC) was detectable, reflecting the 
importance of adequate adherence to medication. YMSM ages 18-24 in iPrEx demonstrated lower PrEP 
efficacy (28%) compared to older participants (56%) and were over 3 times less likely to have drug 
detected in plasma. The iPrEx Open Label Extension14 reported no significant difference of PrEP uptake 
on the basis of age, however, the odds of having detectable drug in plasma significantly decreased as age 
decreased, with those 18 to 24 years of age differing substantially from those 30 and older. In the ATN 
110 trial of young adult MSM, protective levels of adherence (defined by dried blood spot levels 
consistent with ≥ 4 pills/week) declined sharply over time from 56% at week 4 to 34% at week 48 [7]. In 
the ATN 113 trial of adolescent MSM, the declining adherence was even more striking, from 54% at 
week 4 to 22% at week 488. Thus, while PrEP appears to be of interest to YMSM, barriers to adherence 
adversely impact effectiveness. 
For youth, PrEP may only reach its full potential with drugs that do not depend on daily or near-daily 
pill-taking. 
Challenges with adherence to medication are commonplace among adolescents, regardless of whether it 
is adherence to a treatment or prevention regimen. Non-adherence among youth is often a reflection of 
both the biological and behavioral transitions that occur during this developmental time, including 
increased autonomy from parents/guardians, increased importance of peers and corresponding 
vulnerability to peer influence and stigma, and undeveloped cognitive capacity for organization and 
planning. Rates of adherence among adolescents and young adults with chronic illnesses requiring daily 
medication, such as HIV, diabetes, and cancer are consistently low, with estimates often about 50% 
overall.17,18 Similarly, rates of adherence to oral prevention strategies, such as contraception, 
demonstrate similar challenges to daily adherence. Many studies have found that continuation rates are 
lower and pregnancy rates are higher among adolescents using oral contraception versus long-acting 
contraceptives.19,20 Just as increased choice in type and method of delivery of contraceptive methods has 
increased acceptability and effectiveness for contraception21,22, we believe that expanded choices for 
HIV prevention will similarly increase utilization, satisfaction, and effectiveness. 
A recently presented qualitative study investigating PrEP preferences among young MSM supports that 
prevention choice is important for young men. Participants, ages 16-29, reported that injections may be 
more manageable and better for those who have adherence difficulties as well as beneficial for those 
who engage in sex more frequently. However, concerns specific to injectable PrEP were expressed 
regarding severity/duration of side effects, pain, level of protection prior to next injection, distrust of 
medical system and injections, and cost – all issues that must be addressed with further research among 
young populations.23,24 The development of alternative agents for PrEP, with more adherence-friendly 
schedules, could increase prevention choices and increase acceptability. Long-acting injectable agents 
have the potential to prevent HIV acquisition without relying on adherence to a daily oral regimen.25  
Adult safety data on long-acting cabotegravir (CAB LA) will need to be expanded to adolescents in 
order to license the product for youth under the age of 18 


 
HPTN 083-01, FINAL V3.0 
18 of 152 
2 July 2021 
Currently, two parent protocols (HPTN 083 and HPTN 084) are being conducted globally. HPTN 083 is 
a study being done to evaluate the efficacy of CAB LA for PrEP in HIV-uninfected MSM and TGW, 
ages 18 and older, and is enrolling approximately 4,500 MSM and TGW in the Americas, Asia and 
South Africa. HPTN 084 is a study being done to evaluate the safety and efficacy of CAB LA, compared 
to daily oral Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®), for PrEP in approximately 
3,200 HIV-uninfected women ages 18 to 45 years old in sub-Saharan Africa who are at risk for 
acquiring HIV. See Section 1.7.3 for results from the HPTN 083 study. 
Historically, medical treatments applied to children were often based upon testing done only in adults, 
rendering evidence-based treatments less available to children due to their exclusion from studies. Since 
1996, one goal of the National Institutes of Health as well as the US FDA has been to increase the 
participation of children in research so that adequate data can be developed to support treatment (and 
prevention) modalities for disorders and conditions that affect adults as well as children. In order for 
adolescents to access safe and effective new biomedical HIV prevention products at the same time that 
these products are approved and marketed for adults, the scientific development and testing of these 
products for adolescents must proceed concurrently.26 Similarly, adolescents are often excluded from 
prevention intervention trials due to concerns from regulatory or ethics boards as well as investigator 
concerns around the complexity of recruitment/retention and/or fear that adolescent difficulties will 
adversely impact the primary outcomes of the trial.27,28 This exclusion from large Phase 3 trials as well 
as hesitancy to launch youth-focused bridging trials only exacerbates the gaps in HIV prevention 
intervention availability and access, which continues to fuel the HIV epidemic among vulnerable young 
people.  
This trial has been designed as an open label clinical trial. An unblinded, single arm trial is most 
developmentally-appropriate for adolescents, while also minimizing participant and staff burden. The 
design of the parent trials (HPTN 083 and HPTN 084) is quite complicated. They are double-blind, 
double dummy trials with a complex visit schedule and a lengthy commitment for participant 
completion. It is unreasonable and unnecessary to request this type of commitment and burden from 
vulnerable adolescents (and their parents/guardians), when efficacy data can be extrapolated from the 
parent studies. Furthermore, open label prevention studies have demonstrated that product adherence 
improves when participants know what they are taking and can be counseled about the unblinded 
product.29-31 
1.2 Overview of Oral CAB and CAB LA 
The majority of information contained in this section of the protocol is a summary of information 
provided in the CAB Investigator’s Brochure (IB), unless otherwise noted. 
CAB is an investigational HIV integrase strand transfer inhibitor (INSTI) that has attributes favorable 
for both HIV treatment and prevention indications. Currently in Phase 2 and Phase 3 clinical trials, it 
was initially selected for development based on its potential for a high genetic barrier to resistance and a 
PK profile that allows low-dose, once-daily oral dosing or monthly to every 2-month parenteral dosing 
using an aqueous suspension for injection formulation. An oral tablet version of CAB has also been 
developed as lead-in therapy to establish acute safety and tolerability in individual participants prior to 
switching to the long-acting formulation. CAB LA has an absorption half-life 21 to 50 days in adults.  


 
HPTN 083-01, FINAL V3.0 
19 of 152 
2 July 2021 
1.2.1 Non-human Primate Studies Relevant to Rectal Exposures 
CAB LA has demonstrated activity in preventing simian human immunodeficiency virus (SHIV) 
infection in non-human primate models.32 In a preclinical study evaluating the potential of CAB LA for 
PrEP, 2 weekly doses of CAB LA (50 mg/kg intramuscularly [IM]) were highly protective against 
weekly rectal challenges with SHIV162p3 (50% tissue culture infective dose [TCID]50) for up to eight 
exposures. In these protected animals, the plasma concentrations of CAB LA throughout the period of 
virus challenges were comparable to clinically-relevant concentrations in humans. In follow-up studies, 
a single dose of CAB 50 mg/kg IM one week prior to the serial weekly viral challenges with 
SHIV162p3 (50 TCID50) were evaluated. The percent of challenges resulting in infection was calculated 
relative to the plasma CAB protein-adjusted 90% inhibitory concentration (PA-IC90) value. None of 59 
challenges resulted in infection when plasma levels were greater than 3 times the PA-IC90, compared 
with 1 out of 22 challenges resulting in infection when plasma levels were between one to three times 
the PA-IC90, and 11 out of 43 challenges resulting in infection when plasma levels were less than 1 times 
the PA-IC90. Twelve out of 26 challenges resulted in infection in control animals; rectal tissue levels of 
CAB were approximately 20% of plasma levels.33   
1.3 Metabolism 
CAB is highly protein bound in human plasma (>99%). It is a substrate for permeability glycoprotein 
(Pgp), but because of its high permeability, no alteration in absorption would be expected by co-
administration of either Pgp or breast cancer resistance protein (BCRP) inhibitors. Elimination occurs 
predominantly in feces via biliary excretion. Renal excretion is minimal, with less than 1% of the dose 
eliminated in the urine. The primary route of biotransformation is conjugation with glucuronic acid (M1) 
via uridine diphosphate glucuronyltransferase type 1A1 (UGT 1A1).  
1.4 Preclinical Studies 
The CAB toxicology package supports the careful conduct of clinical studies with CAB up to the no 
observed adverse effect level (NOAEL) exposure in the 39-week monkey toxicity study (Week 39 
gender mean AUC0-24 and Cmax of 547 g·h/mL and 34.6 g x h/mL, respectively). The results of the 
multiple dose rat subcutaneous (SC) and IM toxicity study, along with data from the oral toxicity 
program, support the careful conduct of clinical studies with CAB LA up to the mean Cmax plasma 
concentration observed at the NOAEL in the 39-week monkey oral CAB toxicity study (34.6 g/mL) or 
the mean AUC1,440-2,160h following once monthly IM dosing at the NOAEL (75 mg/kg/dose) in the 
3-month rat CAB LA toxicity study (92,566 g x   h/mL). 
In a rat pre- and post-natal study, CAB exposure during pregnancy resulted in increased offspring 
mortality at the highest dose tested (1000mg/kg/day). This is in excess of the established safety limit 
(NOAEL) of 5mg/kg/day. The NOAEL is >20 fold the predicted clinical Cmax and AUC exposures in 
humans for both HIV treatment and prevention. The mechanism for the reduction in viable pups at this 
supratherapeutic dose up to 4 days post-partum is unknown. Clinical dosing in HPTN 077 (a safety, 
tolerability, and PK of CAB LA in HIV-uninfected, low-risk men and women) is approximately 7-fold 
below the NOAEL in 10-day-old rat offspring. Importantly, an early fetal development (EFD) study in 
rats was negative. 


 
HPTN 083-01, FINAL V3.0 
20 of 152 
2 July 2021 
1.5 Dose Rationale 
1.5.1 Oral CAB  
CAB is readily absorbed following oral administration in healthy and HIV-infected participants with a 
median Tmax of approximately two hours. The apparent terminal phase half-life following oral 
administration is approximately 40 hours.   
In a short-term monotherapy study, seven HIV-infected participants received oral CAB 5 mg once daily 
for 10 days, which achieved a geometric mean Day 10 plasma trough concentration (C) of 0.57 g/mL, 
3.4-fold above the PA-IC90 value, and was associated with a mean Day 11 HIV ribonucleic acid (RNA) 
change from a baseline of -2.2 log10 c/mL.34,35 In LATTE, the Phase 2b study in HIV-infected, ART-
naïve adult participants,36 suppression of HIV replication was accomplished with oral CAB at doses of 
10 mg to 60 mg once daily in combination with two nucleoside reverse transcriptase inhibitors (NRTIs), 
and HIV viral load was maintained below 50c/mL at similar rates across oral CAB 10 mg to 60 mg 
doses through >72 weeks when combined with oral rilpivirine (RPV) 25 mg once daily. The geometric 
mean individual average plasma C following oral CAB 10 mg and 30 mg once daily were 1.35 g/mL, 
eight-fold above PA-IC90, and 4.2g/mL, 25-fold above PA-IC90, respectively.   
An oral tablet version of CAB has been developed as lead-in therapy to establish acute safety and 
tolerability in individual participants prior to switching to the long-acting formulation. Oral CAB has 
been studied at doses between 5 mg and 150 mg in HIV-uninfected and HIV-infected adults. The oral 
formulation of CAB has been generally well-tolerated as single or repeated doses in clinical studies of 
HIV-uninfected adults. CAB 30 mg once daily has been used as the oral lead-in the ECLAIR (Phase IIa 
Safety and PK Study of Cabotegravir LA in HIV-uninfected Men), LATTE-2 (CAB + RPV as Long-
Acting Maintenance Therapy), HPTN 077 (A Phase IIa Safety, Tolerability and Acceptability Study of 
an Investigational Injectable HIV Integrase Inhibitor for PrEP in HIV Uninfected Men and Women) 
studies, and 4 Phase III studies in adults - 2 PrEP studies, HPTN 083 and HPTN 084, and 2 treatment 
studies (201584 (FLAIR) and 201585 (ATLAS). Therefore, CAB 30mg once daily has been selected for 
the oral run-in regimen for this study. 
1.5.2 CAB LA  
Through October 2018, approximately 4236 adult participants have been exposed to at least one dose of 
CAB (oral and/or LA) across 18 completed or ongoing Phase 1, 2 & 3 clinical trials (see Table 1.1).  
Table 1.1  Cumulative CAB Exposures from Phase 1 through Phase 3 Clinical Studies Through 
October 2018 
 
Treatment Population/ 
Dose 
Duration 
Completed 
Ongoing/ 
Concluded a 
Total 
Healthy Volunteers/HIV-Uninfected 
 
 
 
5 to 150 mg oral 
Single dose 
208 
0 
208 
10 to 30 mg once daily oral  
10 to 28 days 
293 
1694 
1987 
150 mg every 12 hours oral  
3 doses 
40 
0 
40 
100 – 800 mg IM/SC LA 
Max 763 days g 
230 b 
1377 c 
1607 
Any dose 
 
599 
1694 
2293 
HIV-infected patients 
 
 
 
5 to 30 mg once daily oral (Ph 2a) 
10 days 
15 
0 
15 


 
HPTN 083-01, FINAL V3.0 
21 of 152 
2 July 2021 
10 to 60 mg once daily oral (Ph 2b) 
Max 2247 days h 
0 
181 
181 
30 mg once daily oral (Ph 2b) 
 
0 
1739 
1739 
Up to 800 mg IM LA d 
Max 1477 days g 
0 
1745 e 
1745 
Any dose 
 
15 
1928 
1943 
All participants 
 
 
 
Single dose oral (5 to 150 mg) 
 
208 
0 
208 
Repeat dose once daily oral (5 to 60 mg) 
 
308 
3614 
3922 
150 mg oral every 12 hours x 3 
 
40 
0 
40 
Single or repeat dose LA injection (100 to 800 mg) 
 
230 b 
3122 f 
3352 
Any dose 
 
614 
3622 
4236 
a. Concluded studies: study completed through follow-up; and/or clinical study report is in preparation 
b. 172 participants received both oral and LA dosing 
c. All participants received both oral and LA dosing 
d. Includes 400 mg Q4W and 600 mg Q8W dosing 
e. 1736 participants received both oral and LA dosing 
f. 3113 participants received both oral and LA dosing 
g. Detectable CAB concentrations can remain for up to 72 weeks following the last CAB injection 
h. As of 28 Dec 2014, all participants had transitioned to CAB 30 mg in the Open-Label phase of study LAI116482 
(LATTE-1), therefore, the longer durations apply to the 30 mg dose only 
 
The regimen proposed for this study was evaluated in HPTN 077 Cohort 2.  For the HPTN 077 study, 
participants were low-risk HIV-uninfected individuals at eight sites globally, randomized (3:1) to daily 
oral CAB 30mg (or placebo) for four weeks, followed by CAB (or PBO) 800mg IM at weeks 5, 17, and 
29 (Cohort 1) or 600 mg IM at weeks 5, 9, 17, 25, and 33 (Cohort 2). One hundred ten participants 
enrolled in Cohort 1, 89 in Cohort 2. Ninety-four percent of participants completed the oral phase, 89% 
received at least one injection, and 75% completed all injections, which did not differ by arm, cohort or 
sex. Over 41 weeks, injection site pain and injection site reactions (ISR) were more common in CAB vs. 
placebo. No other differences were found in safety or tolerability. ISR led to injection discontinuation in 
2/134 (1.5%). Cohort 2 dosing consistently achieved plasma trough targets whereas Cohort 1 dosing did 
not. Overall, CAB was well tolerated among low-risk HIV-uninfected men and women.  
In HPTN 077, overall 65% of the study participants were female. Median BMI was 28 kg/m2 in female 
participants and 25 kg/m2 in male participants. Among participants in Cohort 1 (who received a split 
injection of CAB-LA 800mg IM q12 weeks), males had a higher geometric mean Cmax after the first 
injection, but significantly lower trough concentrations than female participants after all three injections. 
Trough CAB levels were below 4X PA-IC90 in 72%, 35%, and 32% of male participants at weeks 17, 
29, and 41, respectively. In contrast, trough CAB levels in female participants were largely at goal 
throughout the trial, with 24%, 5% and 0% of female participants having trough levels below 4X PA-
IC90 at weeks 17, 29, and 41. In Cohort 2 (Figure 1.1) (CAB LA 600mg IM q 8 weeks), male 
participants achieved significantly higher CAB Cmax, AUC0-tau, and Ctrough after the first injection 
than female participants (and overall, participants with lower BMI were observed to have significantly 
higher trough concentrations after the first injection). However, CAB trough levels < 4X PA-IC90 
(between 1 and 4X the PA-IC90) were observed in 5%, 20%, 20%, 16%, and 11% of male participants 
after injections 1, 2, 3, 4, and 5, respectively. For female participants, 21%, 5%, 3%, 0%, and 3% had 
CAB trough levels below 4X PA-IC90 after injections 1, 2, 3, 4, and 5, respectively.  


 
HPTN 083-01, FINAL V3.0 
22 of 152 
2 July 2021 
Figure 1.1: CAB LA PK Profiles following Q8W Dosing in Males and Females (HPTN077, Cohort 
2) 
 
 
During the 76-week follow-up phase of the HPTN 077 study37, differences were observed in the median 
time to undetectable cabotegravir concentrations between men and women: 42.7 weeks (range 20.4-134) 
in men as compared to 66.3 weeks (range 17.7-182) in women. CAB was detectable in plasma in 22% of 
men and 63% of women at 60 weeks and in 13% of men and 44% of women at 76 weeks post the last 
injection). The observed PK in HPTN 077 supported the development of CAB for HIV prevention using 
600mg IM every 8 weeks with a 4-week loading dose for all sexes. 
1.6 Genital Tract (GT) Tissue Levels after Oral and Injectable Administration 
Genital tissue concentrations have been measured after CAB LA 400 mg IM single dose administration 
in 24 healthy men and 15 healthy women. Median cervical and vaginal tissue concentrations ranged 
from 16-28% (overall range 0-70%) of plasma concentrations, roughly 1 x PA-IC90 (0.166 µg/mL). 
Median rectal tissue concentrations were ≤ 8% of plasma concentrations (range 0-20%).37 Further tissue 
studies using single and multiple doses of the 800 mg IM dose are currently ongoing.   
1.7 Pediatric Dosing 
Currently, there is no previous clinical trial experience with oral CAB or CAB LA in humans under 18 
years of age. This protocol will enroll using a weight-based approach rather than age based. This allows 
for an eventual adolescent indication for LA CAB in adolescents at-risk, regardless of age. The 
supplemental adolescent indication for Truvada® was entirely weight-based (down to 35 kg) for 
adolescents at risk of HIV. Also, by not specifying a lower limit of age, this allows sites the flexibility to 
enroll participants that meet the behavioral and physical criteria necessary to qualify. Each site will have 
ethics review and will consider these criteria in light of community standards; and each investigator of 
record will be able to determine whether a candidate is appropriate for enrollment or not. These 


 
HPTN 083-01, FINAL V3.0 
23 of 152 
2 July 2021 
decisions will then be made with consideration for the local context of each site/community, rather than 
arbitrarily choosing what age should be the lower limit.  
 
1.7.1 Preliminary Results MOCHA (IMPAACT 2017)  
The IMPAACT 2017 trial began enrolling in April 2019. IMPAACT 2017 (NCT03497676) is a 
Phase I/II, multi‐center, open‐label, non‐comparative study to confirm the dose and evaluate the 
safety, tolerability, acceptability, and PK of oral CAB, long-acting injectable CAB (CAB LA), 
and long-acting injectable RPV (RPV LA) administered monthly among up to 155 virologically 
suppressed HIV‐1 infected children and adolescents aged 12 to <18. 
 
As of January 2020, 7 adolescent HIV infected participants in IMPAACT 2017 (MOCHA) aged 
12 to 17 years (40 to <50kg: n=4, >50 kg: n=3) had PK collected and analyzed following oral 
CAB 30 mg once daily and three injections of the CAB LA adult monthly regimen (600 mg IM 
initiation injection, followed by two monthly 400 mg IM injections). Median (range) CAB PK 
parameters were within the desired target ranges, specifically Week 2 oral AUC 167.0 (131.1-
326.8) g•h/mL and Week 16 IM trough 2.9 (1.2-6.2) g/mL, and were similar to adult 
exposures (Table 1.2). 
 
Table 1.2: Pharmacokinetic Parameters following Cabotegravir Orally Once Daily and 
Initiation and Monthly Continuation Intramuscular Injections in Adults 
 
Dosing Phase 
Dosage Regimen 
Geometric Mean (5th, 95th Percentile)a 
AUC(0-tau)b 
(mcg•h/mL) 
Ctaub 
(mcg/mL) 
Oral Lead-Inc 
30 mg  
once daily 
145 
(93.5, 224) 
4.6 
(2.8, 7.5) 
Initial Injectiond 
600 mg IM 
Initial Dose 
1,591 
(714, 3,245) 
1.5 
(0.65, 2.9) 
Monthly Injectione 
400 mg IM 
monthly 
2,415 
(1,494, 3,645) 
2.8 
(1.7, 4.6) 
a All pharmacokinetic parameter values based on pooled FLAIR and ATLAS individual post-hoc estimates from 
cabotegravir population pharmacokinetic model (n = 581, 2018N384611_01). 
b tau is dosing interval: 24 hours for oral administration; 1 month for IM injections of extended-release injectable 
suspension. 
c Oral lead-in pharmacokinetic parameter values represent steady-state. 
d Initial injection AUC(0-tau) value includes contribution following oral dosing because the initial injection was 
administered on the same day as the last oral dose; however, the Ctau value at Week 4 reflects the initial injection. 
e Monthly pharmacokinetic parameter values represent Week 48 data. 
 
Preliminary CAB data observed in adolescent participants were compared to a priori predictions 
in adolescents from population PK (POP PK) modelling and simulation (Figure 1.2). The CAB 
POP PK model was developed utilizing exposure data from adult participants (n=1647) in 
clinical studies with efficacious dosing regimens having an acceptable safety profile with Q4W 
and Q8W injections, and simulations were conducted taking into account any potential age and 
weight related impact on PK, to recommend appropriate doses in adolescents that achieve 
comparable exposures to those seen in adults. The preliminary adolescent PK data are in 


 
HPTN 083-01, FINAL V3.0 
24 of 152 
2 July 2021 
agreement with the predicted exposure range and within thresholds (Figure 1.2).  Given the 
strong agreement of observed data with predictions, the model is considered suitable to predict 
exposure in adolescents 35 kg for any dosing regimen. Predicted exposures following CAB LA 
Q8W administration in adolescents are shown in Table 1.2.  
 
 
Figure 1.2: Preliminary Observed CAB concentrations in adolescents compared to model 
predictions based on POP PK analyses from adult studies (IMPAACT 2017 Cohort 1C) 
 
Note: The plots represent the CAB systemic exposure: solid line and shaded band reflect the population 
pharmacokinetic model predictions (median and 90% interval); the dots represent the observed individual subject 
data. The dashed lines represent the maximum observed geometric mean exposure from the TQT study at (22.5 
g/mL) at supratherapeutic doses following 150 mg q12h x 3 and the target threshold concentrations at trough (0.65 
g/mL). 
 


 
HPTN 083-01, FINAL V3.0 
25 of 152 
2 July 2021 
Table 1.3: Predicted Steady State CAB Parameters following CAB LA IM Q8W regimen  
compared with Observed and Estimated data in Adults 
 
 
 
Predicted C (g/mL)b 
Post First Injection 
Post Second Injectionc 
Adolescent Body 
weight 
35 to <50kg 
2.49 [0.98, 4.72] 
2.34 [0.84, 3.98] 
50kg 
1.76 [0.69, 3.49] 
1.76 [0.77, 3.05] 
Observed adult data 
1.50 [0.65, 2.90] a 
1.61 [0.80, 2.99]d 
a. 
Geometric mean [5th and 95th percentile] - Week 8 pre-dose concentrations were obtained following a 
CAB 600 mg IM dose.) 
b. Median [90% prediction Interval] 
c. 
C after second injection is 8 weeks post injection 
d. Geometric mean [5th and 95th percentile] - C at Week 48 with Q8W dosing regimen (ATLAS 2M, 
207966) 
 
1.7.2 Results from HPTN 077 
A population PK model (n=1647) that included data from HPTN 077 (n=134, 89 females, 45 males) and 
15 other studies was used to predict exposures following the proposed CAB LA Q8W regimen in 
adolescents. Gender and BMI are significant covariates affecting the absorption rate following IM 
administration and were retained in the model to extrapolate to smaller adolescent males expected to 
enroll in HPTN 083-01. Model predicted concentrations in adolescent males (simulated with median 
weight and BMI of 63 kg and 21 kg/m2, respectively) to enroll in HPTN 083-01 are similar to adult 
males in HPTN 077 (median weight and BMI of 77kg and 24 kg/m2, respectively) receiving the same 
regimen and below oral dosing, and therefore are expected to be safe in this population (Table 1.4). 
Approximately 95% of male subjects are expected to achieve trough concentrations > 4x PA-IC90 
following the 5th injection. This regimen is currently being evaluated in uninfected adult males and 
females in HTPN 083 and HPTN 084, respectively, and has maintained HIV suppression in infected 
adults when combined with RPV LA (LATTE-2). 


 
HPTN 083-01, FINAL V3.0 
26 of 152 
2 July 2021 
Table 1.4: Predicted CAB Parameters following Injection 5 of the CAB LA 600mg IM Q8W 
Regimen in Male Adolescents compared with Predicted and Observed Data in Male 
Adults in HPTN 077  
Plasma CAB 
Parameter 
((g/mL) 
Male Participants in HPTN 077 
Median 
(range) 
Predicted Exposures 
Male Adolescents 50kg  
(110 lbs.)  
Predicted 
Parameters  
30 mg Once 
Daily 
Observed Data 
600mg IM 
Q8W 
(Injection 5)  
Median 
(90% PI) 
Peds:Adults 
Relative Exposure 
Vs 30mg 
Vs 
600mg 
Oral Cmax or  
C,Wk 34 
(1-week post Inj5) 
7.6 
(4.6 - 12.0) 
3.4 
(1.6 - 12.9) 
5.0 
(2.7, 9.1) 
0.7 
1.5 
Oral C or  
C,Wk 41  
(8-weeks post Inj5) 
4.5 
(2.3 - 7.6) 
1.78 
(0.50 - 4.2) 
1.8 
(0.5, 3.4) 
0.4 
1.0 
 
Plasma CAB will be evaluated during follow up period and but is not expected to be detectable in a 
majority of subjects one year after the final injection.   
Based on adult dosing data and pharmacokinetic modeling, oral CAB 30mg and CAB LA 600mg IM are 
expected to be safe in adolescents and have been selected as the initial regimen for the IMPAACT 2017 
study - the same as the adult CAB regimen in current Phase III studies. While somewhat higher CAB 
plasma concentrations are expected in lower weight adolescent participants, the safety and tolerability 
seen in adults at the higher oral CAB dose of 60 mg daily and CAB LA dose of 800mg q 8 weeks 
tempers any safety concerns.  
Seven uninfected participants in HPTN 077 weighing <50kg at baseline received CAB LA injections 
during the study. Individual W41 Ctau values following final injections in participants <50 kg ranged 
from 0.616 g/mL to 4.17 g/mL (Table 1.3), which is within the range of W41 Ctau for the study 
population overall of 0.203 to 4.72 g/mL for Cohort 1 (n=57) and 0.503 to 4.62 g/mL for Cohort 2 
(n=52) and are consistent with expected concentration targets. Individual t1/2 estimates ranged from 
13.6 days to 90.4 days in participants <50 kg and from 19.8 to 183 days in Cohort 1 overall and from 
13.6 to 241 days in Cohort 2 overall.   


 
HPTN 083-01, FINAL V3.0 
27 of 152 
2 July 2021 
Table 1.5: Select PK Parameters in Participants with Baseline Weight <50kg 
Cohort 
Sex 
Subject 
Baseline 
Weight 
(kg) 
Baseline 
BMI 
(kg/m2) 
Ctau  
(g/mL) 
T1/2 
(day) 
Week 9 
(Initial 
Injection) 
Week 41  
(Final 
Injection) 
Cohort 
1 
F 
257000081 
42.7 
16.5 
0.655 
1.73 
28.3 
F 
264000146 
41.4 
18.2 
1.36 
3.13 
50.3 
Cohort 
2 
F 
261000208 
46.5 
19.4 
4.41 
4.02 
90.4 
M 
261000299 
49.7 
17.0 
2.22 
4.17 
60.8 
F 
263000215 
46.5 
19.4 
2.74 
0.616 
13.6 
F 
263000350 
47.5 
20.3 
2.27 
2.67 
21.9 
F 
264000392 
49.5 
18.4 
3.68 
1.04 
14.5 
Source Data: Listings 6.4, 8.23, 8.24 
Cohort 1:  800mg Q12W x 3 doses 
Cohort 2:  600mg Q8W (Injections 2 administered 4 weeks following injection 1, Injections 3-5 administered 8 week 
following prior injections). 
 
1.7.3 Results from HPTN 083 
On 14 May 2020, the international DSMB met to review safety and efficacy data for the HPTN 083 and 
084 study trials. In HPTN 083, a study among cisgender men and transgender women who have sex 
with men, they reviewed 50 overall HIV infections for an overall HIV incidence of 0.79%. Of those 
infections, 38 occurred in the TDF/FTC arm compared to 12 in the CAB LA arm. Based on this data, the 
DSMB agreed that CAB LA had crossed the prespecified non-inferiority margin and was highly 
effective in preventing HIV infections. The DSMB recommended unblinding of all study participants 
and providing them their choice of study product in HPTN 083. In addition, the DSMB reported no 
safety concerns for either the HPTN 083 or 084 trials.  
On 7 July 2020, at the 23rd International AIDS Conference (AIDS 2020: Virtual), the HPTN 083 study 
team announced that the HPTN 083 clinical trial showed that CAB LA, injected once every 8 weeks, 
was superior to daily oral tenofovir/emtricitabine (TDF/FTC) for HIV prevention amongst the HPTN 
083 study population. A total of 52 HIV infections occurred during follow-up, with 13 infections in the 
CAB arm (incidence rate 0.41%) and 39 infections in the TDF/FTC arm (incidence rate 1.22%). The 
hazard ratio in the CAB versus TDF/FTC arms was 0.34 (95% CI 0.18-0.62), corresponding to a 66% 
reduction in incident HIV infections in study participants given CAB compared to TDF/FTC. These 
results meet the statistical criteria for superiority of the regimen containing CAB compared to TDF/FTC 
in the HPTN 083 study population.37 
 
1.8 Hepatic and Central Nervous System Adverse Events 
As part of the early phase development of CAB (HPTN 077, LATTE and LATTE-2), some participants 
developed transaminase elevations, which were clinically asymptomatic and resolved rapidly with 
cessation of study product.   


 
HPTN 083-01, FINAL V3.0 
28 of 152 
2 July 2021 
In a single-dose study (LAI116815), a healthy male volunteer with a history of prior seizure activity 
(one episode 14 years prior), on no anti-epileptic medication, experienced an unwitnessed seizure event 
270 days after a single injection of CAB LA 400 mg IM. Plasma levels of CAB were undetectable for 4 
months prior to the seizure event. The event occurred in the context of consumption of approximately 10 
cans of beer, and a magnetic resonance imaging (MRI) study was unrevealing for pathology. An 
electroencephalogram was consistent with benign juvenile epilepsy; the participant recovered without 
additional events.   
A participant in the ongoing Phase 2b LATTE-2 trial of HIV-infected individuals received oral 
ABC/3TC with CAB 30 mg daily for 20 weeks, and received ABC/3TC, CAB and oral RPV for 4 
weeks, all without incident or clinically significant AEs or laboratory abnormalities. He was randomized 
to continue CAB LA 400 mg IM + RPV LA 600 mg IM Q4W. On day 349 of overall CAB treatment 
(139 days of oral CAB + 210 days of CAB LA exposure), the participant was found in his apartment by 
emergency personnel unresponsive, unconscious, and having generalized tonic-clonic seizures. The 
participant was hospitalized in the intensive care unit, had recurrent seizures, and was found to have 
anoxic brain injury resulting in death. The participant had no prior history of seizures, and clinical 
history and toxicity screens suggested possible recreational substance use.   
A participant in the healthy volunteer HPTN 077 study, with a prior history of seizures treated with 
Dilantin had been taken off Dilantin 2 years prior to study participation and had been seizure-free. A 
“spell” 1 month prior to study enrollment did not prompt re-initiation of anti-epileptics. Oral CAB 30 
mg (or placebo) was administered for four weeks without incident, and Day 62 after administration of 
CAB LA 800 mg IM x 1 (or placebo), the participant had an unwitnessed seizure event; he was 
subsequently hospitalized for transient dizziness and hemiparesis, for which work-up was unrevealing, 
and resolved with meclizine treatment. The participant recovered without additional events and is not 
planned for additional intraperitoneal (IP) dosing.  
A participant in HPTN 077 without known pre-existing liver disease, and without HIV-infection 
developed Grade 3 ALT elevation after 12 weeks of injectable placebo treatment; the participant was 
asymptomatic, and ALT returned to normal 15 weeks after withdrawal of study product. A serologic and 
ultrasonographic evaluation did not reveal alternative etiology for the ALT elevation; no biopsy was 
performed.   
1.9 Weight gain 
There is emerging evidence from randomized trials that the use of integrase inhibitors could lead to 
significant increases in body weight.39 Two trials of raltegravir and three involving dolutegravir all 
observed greater weight gain increases in integrase containing regimens. These effects appear to vary by 
gender and race, with highest increases observed in women and those of black race. The mechanism for 
this needs to be fully elucidated. These data are from populations receiving treatment and more data is 
needed in healthy HIV uninfected populations using PrEP. HPTN 077 evaluated changes in weight and 
fasting metabolic parameters in 177 HIV-uninfected individuals randomized to cabotegravir or a placebo 
who had received at least one injection. No differences between study groups were found for change in 
weight or fasting metabolic parameters overall, or for subgroups. Among the 146 participants with 
paired weights, between W0 and W41 the median increase in weight for CAB treated participants was 
1.1 (IQR -0.9, +3.0) kg compared to median 1.0 (IQR -1.2, +3.2) kg gained by PBO treated participants 
(=+0.1 kg, p=0.66). The distribution of weight changes across the 41 week treatment period did not 


 
HPTN 083-01, FINAL V3.0 
29 of 152 
2 July 2021 
differ between CAB and PBO-treated participants, nor when divided into the oral phase (=+0.3 kg, 
p=0.6) and the injection phase (=+0.2 kg, p=0.65). A 5% or greater increase in weight from W0 to W41 
was seen in 24 (22%) CAB participants and 7 (18%) of PBO participants (p=0.62).40 
1.10 
Rationale for use of Oral Run-in Prior to Injectable Dosing 
The CAB LA formulation has a PK decay rate that exposes the injected individual to detectable levels of 
CAB for a year or more after an injection (see Section 1.5.2 of the protocol). In order to maximally 
identify any acute toxicity prior to administration of a non-dialyzable, non-removable depot injection, a 
five-week lead-in period of daily oral (short acting) CAB will be employed. This lead-in period will be 
evaluated with serial safety assessments prior to injectable administration. The current plans for product 
labeling should FDA approval be granted include an oral lead-in strategy when adequate safety is 
established after four weeks of oral drug exposure. The 5-week exposure in this study is designed to 
provide un-interrupted study product coverage while awaiting return of the Week 4 safety laboratory 
assessments.   
 
2.0 
STUDY OBJECTIVES AND DESIGN 
2.1 Primary Objectives 
• To evaluate the safety, tolerability and acceptability of CAB LA in healthy, HIV-uninfected male 
adolescents aged below 18 years. 
 
2.2 Secondary Objectives 
• To examine adherence to and timeliness of injections over time among adolescent participants who 
are provided CAB LA and information regarding its safety and unknown efficacy.  
• To examine patterns of sexual risk behavior over time among adolescent participants who are 
provided CAB LA and information regarding its safety and unknown efficacy. 
• To evaluate the safety of CAB LA for 48 weeks of follow-up after final injection. 
• To characterize the pharmacokinetics of CAB LA. 
 
2.3 Study Design and Overview 
We propose a single arm, open label, safety, tolerability, and acceptability study (n= approximately 50) 
in sexually-active, healthy adolescents assigned male sex at birth.  
Study participation includes, Step 1: a 5-week oral CAB 30mg QD safety lead-in followed by a series of 
5 intramuscular (IM) injections of 3 mL (600 mg), administered at 8-week intervals after a 4-week 
loading dose (injections at weeks 5, 9, 17, 25 & 33) in Step 2. Adherence support strategies (e.g., 
counseling, reminders, pill cases) will be included to support pill-taking during the first five weeks and 
to support retention during the injectable phase. A safety visit will follow each injection to ascertain 
pharmacokinetic-peak safety data, including injection site reactions. Step 3: a blood draw visit, the +8 


 
HPTN 083-01, FINAL V3.0 
30 of 152 
2 July 2021 
Week Visit, will follow the last Step 2 injection to monitor CAB drug levels. All participants who have 
received at least one injection will be followed for 48 weeks after their last Step 2 injection. Waning 
levels of cabotegravir (the PK tail) will be covered with locally sourced oral Tenofovir/Emtricitabine 
(Trade name: TDF/FTC, Truvada®) for daily use for 48 weeks or the participant can opt to continue 
CAB LA injections for the duration of Step 3Behavioral and acceptability data will be collected via 
computer-assisted self-interview (CASI).  
Participants who discontinue study product during Step 2 for any reason other than HIV infection or AE 
occurrence will be transitioned to open label Tenofovir/Emtricitabine (Trade name: TDF/FTC, 
Truvada®) for 48 weeks.  
 
Finally, in-depth qualitative interviews will be conducted after the end of Step 2 (Week 34) with 10 
participants (total, across all sites) to explore issues of acceptability and preference for oral tablets 
and/or injections. Additionally, up to 10 parents/guardians of participants (total, across all sites) will be 
asked to participate in in-depth interviews to explore facilitators and barriers to adolescent enrollment in 
biomedical clinical trials as well as parental acceptability of injectable prevention products for youth.  
As previously mentioned, we have chosen an unblinded, single arm trial because it is most 
developmentally-appropriate for adolescents and minimizes participant and staff burden, while also 
offering a more streamlined visit schedule than the parent protocols and, hopefully, promoting study 
drug adherence. 
2.3.1 Participating Sites/Institutions 
Participating sites are listed in the Schema and in the SSP Manual. 
2.3.2 Study Duration 
The initial phase, Step 1, will be an oral lead-in phase of 5 weeks. After that, follow up on study product 
will be for 29 weeks, followed by visits for 48 weeks after the final Step 2 injection per Appendix III or 
IV. Total participant commitment for the entire study is approximately 82 weeks, or approximately 1.5 
years. We anticipate recruitment for the study will take approximately 18 months. 
 
3.0 
STUDY POPULATION 
We are using clinical sites that have proven ability to enroll and retain adolescent participants, astute 
awareness of the developmental and cultural issues experienced by adolescents, as well as outstanding 
productivity with previous bio-behavioral clinical trials. Participants will be recruited from the clinical 
sites’ patient populations, as well as through community-based venues, including working with sites’ 
community partners and community advisory boards, as well as through social media and/or other 
technology-based recruitment methods successfully used in our previous PrEP studies for youth.  
Approximately 50 participants will be included in this study. Each site will be asked to work with its 
Community Advisory Board and outreach, education and recruitment teams to develop a recruitment 
plan appropriate for the local population. Participants will be selected for the study according to the 
criteria in Sections 3.1 and 3.2. Study participants will be recruited as described in Section 3.3. 
Requirements related to participant retention and withdrawal from the study are described in Sections 


 
HPTN 083-01, FINAL V3.0 
31 of 152 
2 July 2021 
3.5 and 3.6, respectively. Individual sites will be given enrollment targets such that overall cross-site 
enrollment meets overall protocol goals.    
3.1 Inclusion Criteria 
Male adolescents who meet the following criteria are eligible for inclusion in this study:  
3.1.1 Assigned male at birth (includes MSM, TGW, and gender non-conforming people) 
3.1.2 At enrollment, aged below 18 years* 
3.1.3 At enrollment, body weight ≥ 35 kg (77 lbs.)* 
3.1.4 Willing to provide written informed assent/consent for the study and/or able to obtain  
 
 
written parental/guardian informed consent;  
• If not of legal age or otherwise not able to provide independent informed consent as determined by 
local law and consistent with site IRB/EC policies and procedures: Parent or legal guardian is 
willing and able to provide written informed consent for study participation and potential 
participant is willing and able to provide written assent for study participation.  
• If of legal age or otherwise able to provide independent informed consent as determined by local law  
and consistent with site IRB/EC policies and procedures: Willing and able to provide written 
informed consent for study participation. 
3.1.5 Self-reported sexual activity with a male in the past 12 months;  
3.1.6 In general, good health, as evidenced by the following laboratory values:  
• Non-reactive / negative HIV test results**,  
• Absolute neutrophil count > 799 cells/mm3, ± 
• Platelet count ≥ 100,000 cells/mm3, 
• Hemoglobin > 11g/dL, ± 
• Calculated creatinine clearance ≥ 60 mL/minute using modified Schwartz equation (< 
grade 2),  
• Alanine aminotransferase (ALT) < 2.0 times the upper limit of normal (ULN) and 
total bilirubin (Tbili) ≤ 2.5 x ULN, 
• Hepatitis B virus (HBV) surface antigen (HBsAg) negative and accepts vaccination,  
• HCV Antibody negative.  


 
HPTN 083-01, FINAL V3.0 
32 of 152 
2 July 2021 
3.1.7 Willing to undergo all required study procedures  
 
3.1.8 If currently on PrEP from a non-study source, willing to stop said PrEP prior to   
 
 
enrollment and agree to switch to oral CAB for the lead-in period and CAB LA   
 
 
injections. 
 
*Please see Section 1.7 for explanation. 
**HIV-uninfected, based on HIV test results obtained at Screening and at the Enrollment visit. All HIV 
test results from the Screening visit must be obtained and must all be negative/non-reactive. This 
includes testing for acute HIV infection, which must be performed within 14 days of Enrollment. 
Individuals who have one or more reactive or positive HIV test result(s) will not be enrolled, even if 
subsequent confirmatory testing indicates that they are not HIV-infected (see SSP Manual).    
± Participants below the cutoff may be considered for enrollment at the discretion of the PI and in 
consultation with the CMC if the PI can demonstrate that participant is in general good health despite 
being below the cutoff. 
3.2 Exclusion Criteria 
Male adolescents with any of the following criteria will be excluded from the study:  
3.2.1 Co-enrollment in any other HIV interventional research study or other concurrent studies  
 
 
which may interfere with this study (as provided by self-report or other available   
 
 
documentation);  
3.2.2 Past or current participation in HIV vaccine trial with exception for participants who can  
 
 
provide documentation of receipt of placebo;  
3.2.3 Exclusively had sex with biological females in lifetime; 
3.2.4 In the last 6 months (at the time of screening):  
• active or planned use of any substance which would, in the opinion of the site 
investigator, would hinder study participation (including herbal remedies), as 
described in the IB or listed in the SSP, and/ or Protocol Section 4.4, 
3.2.5 Known history of clinically significant cardiovascular disease, as defined by  
 
 
 
history/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass  


 
HPTN 083-01, FINAL V3.0 
33 of 152 
2 July 2021 
 
 
grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or  
 
 
any clinically significant cardiac disease;  
3.2.6 Inflammatory skin conditions that compromise the safety of intramuscular (IM)   
 
 
injections;  
3.2.7 Tattoo or other dermatological condition overlying the buttock region that may interfere  
 
 
with interpretation of injection site reactions;  
3.2.8 Current or chronic history of liver disease (e.g., non-alcoholic or alcoholic  
 
 
 
steatohepatitis) or known hepatic or biliary abnormalities (with the exception of Gilbert's  
 
 
syndrome, asymptomatic gallstones, or cholecystectomy);  
3.2.9 Known history of clinically significant bleeding;  
3.2.10 Surgically-placed or injected buttock implants or fillers, per self-report. Contact the CMC 
 
 
for guidance regarding questions about individual cases;  
3.2.11 A history of seizure disorder, per self-report;  
3.2.12 Medical, social, or other condition that, in the opinion of the site investigator, would  
 
 
interfere with the conduct of the study or the safety of the participant (e.g., provided by  
 
 
self-report, or found upon medical history and examination or in available medical  
 
 
records);  
3.2.13 Plans to move out of the geographic area within the next 18 months or otherwise unable  
 
 
to participate in study visits, according to the site investigator. 
3.3 Recruitment Process 
The study will be targeted towards at-risk, sexually active adolescent populations of MSM in the US. 
Enrollment will occur over approximately 18 months.  
Sites will be responsible for developing appropriate recruitment processes that are geared toward their 
respective local communities. All advertising materials must undergo approval by each participating 
site’s Institutional Review Board (IRB)/Ethics Committee (EC).  
Sites will implement wide-reaching educational efforts, community engagement, and multimedia 
advertising including rapidly changing and adaptive social media strategies to reach young populations. 
Participant retention during prolonged follow-up will be accomplished using study-visit incentives as 
permitted by local IRBs at the maximum permissible level. 
3.4 Co-Enrollment Guidelines 
Participants in this study will not be allowed to take part in other concurrent interventional research 
studies during their participation in the study. This is due in part to concerns about: 1) participant study 
burden, 2) limitations on per-unit-time phlebotomized blood volumes, and 3) to avoid confounding in 
the interpretation of the study data.  


 
HPTN 083-01, FINAL V3.0 
34 of 152 
2 July 2021 
3.5 Participant Retention 
Once a participant enrolls in this study, the study site will make every effort to retain the participant for 
the entire follow-up period. Study site staff are responsible for developing and implementing local 
standard operating procedures to target this goal. Components of such procedures may include: 
• Thorough explanation of the study visit schedule and procedural requirements during the informed 
consent process with both participants and parents/guardians and re-emphasis at each study visit. 
• Thorough explanation of the importance of adherence/retention to the overall success of the study. 
• Collection of detailed locator information at the study Screening Visit, and active review and 
updating of this information at each subsequent visit, including where the participant lives and other 
locator venues, and parents/guardians or other family members.  
• Use of appropriate and timely visit-reminder mechanisms, including SMS/WhatsApp/text 
messaging. 
• Immediate and multifaceted follow-up on missed visits, including SMS/WhatsApp/text messaging. 
• Mobilization of trained staff to complete in-person contact with participants at their homes and/or 
other community locations. 
• Regular communication with the study community at large to increase awareness about HIV/AIDS 
and explain the purpose of HIV prevention research and the importance of completing research study 
visits. 
• Incentives or reimbursements as permitted by local IRB/ECs.  
3.6 Participant Withdrawal 
Regardless of the participant retention methods described in Section 3.5, participants (or their 
parents/guardians if under legal age of consent) may voluntarily withdraw from the study for any reason 
at any time.  
The IoR also may withdraw participants from study product dosing in order to protect their safety and/or 
if they are unwilling or unable to comply with required study procedures after consultation with the 
Protocol Chair, DAIDS Medical Officer, Statistical and Data Management Center (SDMC) Protocol 
Statistician, representatives from the Laboratory Center (LC), the Leadership and Operations Center 
(LOC) Clinical Research Manager (CRM), and others. 
Participants may be withdrawn from the study if the study sponsor, government or regulatory authorities 
(including Office for Human Research Protections [OHRP] and the FDA) or site IRBs/ECs, or ViiV 
terminate the study prior to its planned end date. 
Every reasonable effort will be made to complete a final evaluation of participants who terminate study 
product prior to the final protocol-dictated study week, and study staff will record the reason(s) for all 
withdrawals from the study product in participants’ study records. In such cases, the IoR or designee 
must contact the CMC for guidance regarding final evaluation procedures.     


 
HPTN 083-01, FINAL V3.0 
35 of 152 
2 July 2021 
4.0 
STUDY PRODUCT CONSIDERATIONS 
Site pharmacists should consult the Pharmacy Guidelines and Instructions for DAIDS Clinical Trials 
Networks for standard pharmacy operations. Refer to study schema on page 15 for an overview of steps 
and study design, and to the investigator’s brochures (IBs) for further information about the study 
products. 
 
4.1 Study Product Regimens/Administration/Formulation Content 
Study Product Regimens 
Step 1 – Oral Run-in Phase  
• CAB 30 mg tablet, one tablet orally once daily for five weeks, with or without food  
Step 2 – Injection Phase  
• CAB LA 600 mg administered as one 3 mL (600 mg) IM injection in the gluteal muscle 
at weeks 5, 9, 17, 25, and 33 (5 injections, administered at 8-week intervals after a 4-
week load) 
• A safety visit will follow each injection to ascertain safety data, including injection site 
reactions 
Step 3 – Follow-up Phase 
All participants who have received at least one injection will be followed for 48 weeks after their last 
injection, beginning with a blood draw visit, +8 Week Visit, that will follow eight weeks after the last 
injection to monitor CAB drug levels. Waning levels of cabotegravir (the PK tail) will be covered with 
locally sourced oral Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®)) for daily use for 48 
weeks. Participants will also have the option to remain on CAB LA injections as one 3 mL (600 mg) IM 
every 8 weeks for 48 weeks, should they choose.. 
4.1.1 Oral Product 
Step 1 – Oral CAB tablets 30 mg are formulated as white to almost white oval-shaped film-coated 
tablets for oral administration. The tablets are packaged in high density polyethylene (HDPE) bottles 
with child-resistant closure that include an induction seal. The bottles contain 30 tablets and a desiccant. 
The bottles should be stored up to 30oC (86oF) and protected from moisture.  
Step 3 – Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®) is a fixed dose combination tablet 
containing 200 mg of emtricitabine (FTC) and 300 mg of tenofovir disoproxil fumarate 
(Tenofovir/Emtricitabine [TRADE NAME: TDF/FTC, TRUVADA®]) in each tablet. The tablets must 
be stored as per the manufacturer’s recommendation. Refer to the package insert for recommended 
storage conditions. 


 
HPTN 083-01, FINAL V3.0 
36 of 152 
2 July 2021 
4.1.2 Injectable Suspension 
The CAB study product (oral and LA injectable) being tested in this study is investigational and not yet 
approved by the US FDA for the treatment or prevention of HIV-1 infection. Further information on the 
study product is available in the IB, which will be provided by the DAIDS Regulatory Support Center 
(RSC). 
CAB LA formulation 
CAB LA is formulated as a sterile white to slightly pink colored suspension containing 200 mg/mL of 
CAB LA for administration by IM. The product is packaged in a 3 mL (600mg) vial.  The total amount 
to be administered to each participant is 3 mL (600 mg) per intramuscular (IM) injection. The 
formulation does not require dilution prior to administration. CAB LA injectable suspension is to be 
stored up to 30oC (86oF), do not freeze.  
The investigational pharmacist(s) must be proficient in the preparation of study products using aseptic 
technique under a pharmacy biological safety cabinet (BSC) Class II or better isolator. Local regulations 
and site institutional policies and procedures for use of personal protective equipment, such as gloves, 
gowns, masks, and safety glasses, must be followed.  
One syringe containing 3 mL (600 mg) of CAB LA study product must be prepared using aseptic 
technique under a pharmacy BSC/isolator.  
Materials required for preparation and administration: 
1. One CAB LA 600 mg/3 mL vial 
2. Becton Dickinson (BD) 5-mL Syringe, Luer-Lok Tip, Product No.: 309646 or equivalent 
3. Needle for aspiration: BD general use sterile hypodermic needle, 21G x 1½ inch (e.g. 
    PrecisionGlide Needle, Product No.: 305165 or equivalent) 
4. Needle for intramuscular injection: BD IM sterile hypodermic needle, 23G x 1½ inch 
    (e.g. PrecisionGlide Needle, Product No.: 305194 or equivalent)  
 
Preparation Steps: 
 
1 Remove one CAB LA 600 mg/3 mL vial from storage. If vials are stored in the refrigerator 
(2°C to 8°C), remove vial from the refrigerator and wait at least 15 minutes to equilibrate to 
room temperature. 
2. Vigorously shake the vial for a full 10 seconds, by shaking the vial with long arm movements. 
3. Invert the vial and inspect to ensure uniform suspension. If solid remains undispersed, repeat 
Steps 2-3 until all material is uniformly suspended. 
NOTE: It is normal to see small air bubbles at the end of shaking the vial for re-suspension. 
 
4. Using aseptic technique under a pharmacy BSC/isolator, flip off the plastic cap from the vial. 
Wipe the top of the vial with an alcohol pad and allow to dry. Do not touch the rubber stopper 
at any time. 


 
HPTN 083-01, FINAL V3.0 
37 of 152 
2 July 2021 
5. Remove a 5-mL syringe and a 21G x 1½ inch needle for aspiration. Attach the needle to the 
Luer connection of the syringe. 
6. With the needle sheath on, pull the syringe plunger rod to allow approximately 1 mL of air into 
the syringe. Remove the needle sheath. 
7. Push the needle through the vial stopper and inject approximately 1 mL of air into the vial.   
8. Withdraw the entire contents of the vial into the syringe. Since the suspension can contain 
some air after having shaken the vial, withdraw all suspension from the vial in order to be able 
to de-aerate the syringe properly. 
9. Record the time that the suspension was withdrawn from the vial into the syringe. 
10. Remove the needle that was used to withdraw the suspension into the syringe and discard the 
needle.  
11. Attach a 23G x 1½ inch needle for intramuscular injection to the Luer connection of the 
syringe. Remove the needle sheath from the needle. 
12. De-aerate the syringe by first tapping a finger against the syringe and then by moving the 
plunger rod carefully forward with the needle in the upright position until the first drop of 
suspension appears. Remove the excess suspension in order to administer the correct volume (3 
mL). If needed, collect the excess suspension in a beaker in order to avoid spilling. 
 
After withdrawal of the suspension from the vial into a syringe, it is recommended to inject the 
suspension immediately. Do not exceed 2 hours between withdrawing the contents of the vial into a 
syringe (Step 8) and administration to the study participant.   
 
The prepared CAB LA suspension in a syringe must be stored at controlled room temperature between 
20°C to 25°C from the time it is withdrawn into a syringe to the time it is administered. 
 
Any entered vials or expired filled syringes should be disposed of in accordance with institutional or 
pharmacy policy. 
 
4.1.3 IM Dosing Considerations 
IM injections are administered into the gluteus muscle (gluteus medius method preferred) using a needle 
of appropriate gauge and length (recommended 1.5” 23-gauge needle for CAB LA). The needle should 
be long enough to reach the muscle mass and prevent study drug from seeping into subcutaneous tissue, 
but not so long as to involve underlying nerves, blood vessels, or bone. Variable needle lengths and/or 
needles with different gauge (21 to 25 gauge) are permitted if needed to accommodate individual body 
type.  Longer needle lengths may be required for participants with higher body mass indexes (BMIs, 
example ≥ 30), to ensure that injections are administered intramuscularly as opposed to subcutaneously.  


 
HPTN 083-01, FINAL V3.0 
38 of 152 
2 July 2021 
4.2 Study Product Acquisition and Accountability 
The CAB study products (oral and LA injectable) for Steps 1, 2 and 3 are being provided by ViiV 
Healthcare. For Step 3, the sites will provide locally sourced Tenofovir/Emtricitabine (Trade name: 
TDF/FTC, Truvada®) for 48 weeks after the participants’ last CAB LA injection. 
4.2.1 Study Product Acquisition 
The CAB study products (oral and LA injectable) will be supplied through the National Institute of 
Allergy and Infectious Diseases (NIAID) Clinical Research Products Management Center (CRPMC). 
The study site pharmacist can obtain all the study products through the CRPMC by following the 
instructions in the Pharmacy Guidelines and Instructions for DAIDS Clinical Trial Networks, and 
instructions in the SSP Manual.    
Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®) will be obtained locally by the sites.  
4.2.2 Study Product Accountability 
The site pharmacist is required to maintain complete records of all study products received from the 
CRPMC and subsequently dispensed to study participants. All study products must be stored in the 
pharmacy. All unused study products must be returned to the CRPMC after the study is completed, 
terminated or otherwise instructed by the study sponsor. The procedures to be followed are provided in 
the Pharmacy Guidelines and Instructions for DAIDS Clinical Trials Networks. 
4.3 Toxicity Management 
Toxicity management guidelines can be found in Appendix VI.    
4.4 Concomitant, Prohibited, and Precautionary Medications 
In order to avoid adverse events caused by drug interactions, whenever a concomitant medication is 
taken, site staff should review the concomitant medication's and study product’s most recent package 
insert (PI - for Truvada®) and investigator’s brochure (IB - for cabotegravir) to obtain the most current 
information on drug interactions and contraindications.  Concomitant medications (prescription and non-
prescription) should be administered only as medically necessary during the study.  
After Enrollment, for any drug listed in the Truvada® PI or cabotegravir IB, it is required that the HPTN 
083-01 CMC be notified for recommendations for continuing or stopping (or holding) study product.     
Experimental agents not otherwise specified in the SSP Manual may not be administered. Precautionary 
and prohibited medications include: 
Cabotegravir: 
• 
Not to be administered concurrently: 
o Cytotoxic chemotherapy or radiation therapy 
o Systemically administered immunomodulators 
 


 
HPTN 083-01, FINAL V3.0 
39 of 152 
2 July 2021 
▪ NOTE: Stable physiologic glucocorticoid doses (defined as prednisone ≤15 mg/day or 
equivalent as a stable or tapering dose) are not prohibited. Use of corticosteroids for an 
acute condition such as asthma exacerbation or receiving a short course (defined as ≤2 
weeks of pharmacologic glucocorticoid therapy) is also not prohibited. 
o barbiturates 
o carbamazepine 
o oxcarbazepine 
o phenytoin 
o pheonobarbital 
o rifabutin 
o rifampin 
o rifapentine 
o St. John’s wort 
 
• 
Prohibited within 7 days before and 7 days after an injection 
o high dose aspirin (>325 mg per day) 
o anagrelide 
o apixaban 
o argatroban 
o bivalirudin 
o clopidogrel 
o dabigatran 
o dalteparin 
o enoxaparin 
o fondaparinux 
o heparin 
o lepirudin 
o prasugrel 
o rivaroxaban 
o ticagrelor 
o ticlopidine 
o warfarin 
 
• 
Oral formulation precautions 
o Antacid products containing divalent cations (e.g., aluminum, calcium, and magnesium) must be 
 
taken at least 2 hours before or at least 4-6 hours after the oral CAB administration  
 
Truvada®: 
 
• 
Medications containing the following ingredients should not be administered concurrently: 
o emtricitabine or tenofovir disoproxil fumarate (e.g. ATRIPLA®, COMPLERA®, EMTRIVA, 
 
GENVOYA®, ODEFSEY®, STRIBILD®, or VIREAD, Descovy®). 
o lamivudine (e.g. Combivir, Dutrebis, Epivir, Epivir-HBV, Epivir A/F, Epzicom, Triumeq, or 
 
Trizivir) 
o adefovir (e.g. HEPSERA®) 
o tenofovir alafenamide (e.g. Vemlidy) 


 
HPTN 083-01, FINAL V3.0 
40 of 152 
2 July 2021 
o didanosine (e.g. Videx EC) 
o atazanavir (e.g. Reyataz, Evotaz (atazanavir/cobicistat)) 
o ledipasvir/sofosbuvir (e.g. HARVONI®) 
o darunavir (e.g. Prezista) 
o lopinavir/ritonavir (e.g. Kaletra) 
o orlistat (e.g. Alli, Xenical) 
 
• Co-administration of the following drugs should be clinically monitored by site clinician, as per 
considerations below: 
o Drugs that are eliminated by active tubular secretion (e.g. drug, cidofovir, ganciclovir, 
valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple 
NSAIDS), as these may increase concentrations of emtricitabine, tenofovir, and/or the co-
administered drug.   
o Drugs that decrease renal function (e.g., cause nephrotoxicity) as these may increase 
concentrations of emtricitabine and/or tenofovir. 
• NOTE:  Please report to the CMC if a participant takes a total daily dose of NSAIDS that meets 
or exceeds high dose for MORE than 72 consecutive hours. 
• NOTE:  Acyclovir and valacyclovir may be used when indicated. If needed for treatment – sites 
do NOT need CMC permission for the use of these products, but sites should counsel the 
participant to increase hydration to avoid additive nephrotoxicity; no additional laboratory 
monitoring is required per protocol.  
Further information regarding prohibited and precautionary concomitant medications can be found in the 
SSP Manual and IB. The SSP Manual will be revised (as a whole or as a Memorandum of Changes) and 
re-issued when changes are made.   
All concomitant medications/preparations (prescription and non-prescription) including 
alternative/complementary medications/preparations (e.g., herbs, vitamins, etc.) taken within 30 days 
prior to enrollment and anytime thereafter during study participation will be collected in the study 
participant’s chart and on study case report forms (CRFs).  
5.0 
STUDY PROCEDURES 
Overviews of the study visit and procedures schedules are presented in Appendices I to IV, and 
Appendix V (for suspected and/or confirmed HIV infection). Presented below is additional information 
for visit-specific study procedures. Detailed instructions to guide and standardize all study procedures 
across sites are included in the SSP Manual. 
5.1 Screening 
It is the responsibility of the local site to determine the best approach to screening.  Written informed 
consent and assent (as appropriate) will be obtained before any study procedures are initiated. Both 
clinical and laboratory evaluations will occur at this visit (see Appendix I, Schedule of Evaluations for 


 
HPTN 083-01, FINAL V3.0 
41 of 152 
2 July 2021 
Oral Phase – Step 1). Screening procedures may occur over one or more visits. The SSP Manual 
provides additional information regarding the procedures outlined below, including clinical and 
laboratory procedures and requirements. Enrollment must occur within 30 days of specimen collection at 
Screening for the clinical and laboratory evaluation and procedures (except for HIV RNA testing 
samples, which must be collected and results obtained within 14 days before enrollment).  
Sites will follow the HIV testing algorithm for Screening included in the SSP Manual. If a 
reactive/positive/indeterminate result is obtained for any HIV test, the person is not eligible for the 
study.  Additional testing to confirm suspected HIV infection during Screening will be performed in 
accordance with local guidelines. If HIV infection is confirmed, participants will receive counseling and 
be immediately linked to care either at the study site or other qualified adolescent competent clinic, as 
necessary.   
Individuals deemed not eligible will be informed that they do not meet the elibility criteria for the study 
and will be referred for appropriate medical care, if necessary.   
Potential participants may be rescreened once at the discretion of the IoR or their designee.  Further re-
screening for administrative reasons may be permitted with the approval of the CMC. However, 
potential participants with clinically-significant cardiovascular disease as outlined in the exclusion 
criteria in Section 3.2, or any reactive HIV test, may not be re-screened. Participants with symptoms 
concerning for acute HIV infection (per IoR or designee) may be re-screened in consultation with the 
CMC, once appropriate testing has ruled out acute HIV infection.      
5.2 Enrollment  
Baseline/Enrollment/Week 0 Visit 
Both clinical and laboratory evaluations will occur at this visit, along with behavioral and acceptability 
assessments, including administration of the Patient Health Questionnaire-9 (PHQ-9). See Appendix I 
Schedule of Evaluations for Oral Phase – Step 1 for details.  
All HIV test results including testing for acute HIV from Screening, which must be performed within 14 
days of Enrollment, and at least one HIV test result from Enrollment must be available and confirmed to 
be negative/non-reactive PRIOR to provision of study product.  Results from the chemistry testing, liver 
function tests (LFTs), lipid profile, hematology testing, and urinalysis from this visit are NOT required 
prior to enrollment.   
Eligible participants will be reminded that the use of anticoagulant and/or antiplatelet medications as 
outlined in the SSP Manual are prohibited within seven days before and seven days after injections. 
Reminders will be built in to the concomitant medication history.     
Participants will meet with study staff to receive education and information about adherence during the 
oral phase, identify potential barriers to adherence for the participant, and decide on adherence support 
strategies that will facilitate adherence. During counseling, participants will be offered supportive tools 
such as discrete pill containers, mobile reminder tools including text messaging and/or mobile app alerts, 
and weekly telephone check-ins from study teams. 


 
HPTN 083-01, FINAL V3.0 
42 of 152 
2 July 2021 
All behavioral assessment measures will be programmed into CASI, with the exception of the PHQ-9, 
which is an eCRF administered only at Enrollment. Measures have been previously used either in 
adolescent biomedical prevention trials or in the Phase III adult trials of cabotegravir (HPTN 083/084).  
At the end of this visit, participants will be dispensed oral cabotegravir, with first dose directly observed 
by study staff. Study product must be dispensed with instruction to participants. 
5.3  Step 1, Oral Run-in Phase: Safety Visits   
Oral Run-in Safety Visits at Weeks 2 and 4  
There will be 2 brief follow-up visits during the oral phase of cabotegravir for the purpose of safety and 
adherence checks. Both clinical and laboratory evaluations will occur at these visits (see Appendix I 
Schedule of Evaluations for Oral Phase – Step 1). Adherence counseling will be provided at both Weeks 
2 and 4 to visit to address barriers to daily pill taking, as well as remind participants of adherence 
support options available to them. Pill counts will occur at these visits and participants will take a dose 
directly observed by study staff at each of these visits. 
Participants with pill counts resulting in less than 50% adherence at the Week 4 visit will not be allowed 
to transition to Step 2. Anyone not moving to Step 2 will be terminated from the study. 
Investigators should contact the CMC at 083-01cmc@hptn.org if a participant has missed or delayed 
week 4 visit or has not had sufficient oral drug exposure during the four-week oral run-in period to 
transition to step 2.  
5.3.1 Management of Participants with AEs during Step 1 – Oral Phase 
The oral run-in (Step 1) is included to reduce risk to participants. Participants with significant, negative 
side effects to oral study product will not continue on to Step 2, the Injection Phase.  See Table 5.1 for 
brief instruction and Appendix VI, Toxicity Management, for detailed instruction on participant 
management. All AEs are to be followed until they return to < Grade 2. 
 
Table 5.1.  Management of Participants with AEs in Step 1 
Grade of AE 
Brief Instruction 
Grade 1 AE 
Proceed with SOE and to Step 2 
Grade 2 AE, excluding ALT 
Proceed with SOE and to Step 2 
Grade 2 ALT 
At Enrollment or Week 2 → continue oral product, repeat 
ALT labs in 1 week 
At Week 4→ continue oral CAB, repeat ALT labs in 1 week 
If result is < Grade 1, participant may move to Step 2 if 
otherwise qualifies; 


 
HPTN 083-01, FINAL V3.0 
43 of 152 
2 July 2021 
If result is > Grade 2, permanently discontinue oral CAB, do 
not move to Step 2 and repeat ALT weekly until < Grade 1, 
then terminate from study 
Grade 3 AE, excluding ALT & 
CPK 
Report to CMC and if determined to be: 
• Related AE→ permanently stop oral product, follow 
until stabilizes and then terminate from study 
• NOT related AE→ follow CMC guidance 
Grade 3 ALT 
Report to CMC  
 
Permanently discontinue oral CAB, do not move to Step 2 
and repeat ALT weekly until < Grade 1, then terminate from 
study 
Grade 3 CPK + < Grade 3 ALT 
Report to CMC for adjudication 
Grade 4 AE, excluding ALT & 
CPK 
Report to CMC 
 
Permanently stop oral product, follow until stabilizes and then 
terminate from study 
Grade 4 ALT 
Report to CMC 
Regardless of CPK permanently stop oral product, repeat 
ALT labs weekly until < Grade 1, then terminate from study 
Grade 4 CPK + < Grade 3 ALT 
Report to CMC for adjudication  
5.4 Transitioning from Step 1 to Step 2 
Conditions in Step 1 that could disqualify a participant from transitioning to Step 2 are as follows: 
• Pill count suggestive of less than 50% adherence at the Week 4 visit; 
• Missed or delayed Week 4 visit; 
• Specific AEs per Table 5.1; 
• At substantial risk of HIV infection and/or qualifies for oral PrEP by local guidelines; 
• Any HIV reactive/positive test (see SSP). 
 
If any of the above conditions occur, investigators should notify the HPTN 083-01 CMC at 083-
01cmc@hptn.org within one week of awareness for final determination of fitness to enter Step 2.  


 
HPTN 083-01, FINAL V3.0 
44 of 152 
2 July 2021 
5.4.1 Early Discontinuation in Step 1 
Participants who do not enter Step 2 will discontinue study follow-up. Prior to termination, study staff 
will complete study evaluations due at the Week 4 visit in Appendix I, if possible. All appropriate 
referrals will be made to primary care service providers for sexual reproductive health and HIV 
prevention.  
5.5 Step 2, Injection Phase: Injection Visits  
Injection Phase Injection Visits at Weeks 5, 9, 17, 25, and 33  
All HIV test results from previous visits and at least one HIV test result from the current visit (from 
blood drawn that same day) must be available and confirmed to be negative/non-reactive PRIOR to 
injection of study product. The injection may NOT be given if any HIV test is reactive/positive. For 
management of participants with an HIV-positive test, see Section 5.10. 
Results from the other clinical and laboratory evaluations (e.g., chemistry, LFTs, hematology) from 
previous visits must be available and be reviewed by the IoR or their designee prior to provision of study 
product. Results from STI tests do not need to be reviewed prior to provision of study product. For 
management of participants with AEs, see Appendix VI, Toxicity Management. 
During Step 2, the injection phase of the study, all participants will have brief safety visits one week 
after each injection. Both clinical and laboratory evaluations will occur at the injection visits as well as 
CASI administration for either behavioral or acceptability assessments (see Appendix II. Schedule of 
Evaluations for Injection Phase – Step 2). 
5.6 Step 2, Injection Phase: Safety Visits  
Injection Phase Safety Visits at Week 6, 10, 18, 26, and 34 
During the injection phase of the study, all participants will have brief safety visits one week after each 
injection. Blood will also be collected at these visits to monitor drug levels of CAB. A three-month 
supply of Tenofovir/Emtricitabine [TRADE NAME: TDF/FTC, TRUVADA®]) will be provided at 
Week 34, if the participant chooses oral follow-up (vs. CAB LA). 
5.7 Step 3, Follow-up Phase 
Follow-up Phase  
All participants will be followed for 48 weeks following their last injection in Step 2 (per Appendix III 
and IV) and will have the choice of continuing on CAB LA or being provided with 
Tenofovir/Emtricitabine (Trade Name: TDF/FTC, Truvada®)  If participants would like to switch from 
TDF/FTC to CAB LA in Step 3, that is allowable, but it will not lengthen Step 3. 
Step 3 will begin with the +8 Week Visit, in which participants who received the Week 33 injection will 
return for a blood draw eight weeks afterwards, in order to complete PK monitoring of drug levels of 
CAB. Participants who do not receive the week 33 injection will have a +8 Week Visit after their last 
injection visit and continue to be followed per the Step 3 Follow-up Phase.  


 
HPTN 083-01, FINAL V3.0 
45 of 152 
2 July 2021 
Both clinical and laboratory evaluations will occur during follow-up phase visits as well as CASI 
administration for either behavioral or acceptability assessments (see Appendices III. and IV.: Schedule 
of Evaluations for Follow-up Phase – Step 3-Oral PrEP and Step 3-Injection).  
5.8 Standard of Care (SOC) Counseling for all Participants 
5.8.1 HIV and Risk Reduction Counseling 
HIV testing and risk reduction counseling will be provided at each study visit, in accordance with local 
SOC, and will include messaging about consistent condom use. Condoms will be offered to all 
participants at each study visit consistent with local standards and oral PrEP referrals made as desired.  
Post-exposure Prophylaxis (PEP) 
At any time during study participation, any participant who expresses concern about a potential HIV 
exposure will be referred for PEP services. Any participant receiving PEP will temporarily hold study 
product. Participants may qualify to resume study product dosing and remain in follow-up, after 
consultation with the HPTN 083-01 CMC at 083-01cmc@hptn.org 
5.8.2 Adherence Counseling and Monitoring 
The study will provide adherence support/counseling at baseline and at all follow-up visits for all 
participants and will be tailored to participants’ current study Step. During Step 1, participants will 
receive counseling focused on adherence to the oral CAB and messages about ensuring adequate dosing 
for safety prior to proceeding to Step 2. During Step 2, the importance of returning for injection visits on 
or as close to the scheduled date as practical will be emphasized. During Step 3, the focus will be on 
adherence to oral Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®) PrEP.  
5.9 Injection Visit Windows 
The visit windows for all visits, including injection visits, are outlined in the SSP Manual. Refer to SSP 
for instruction on managing participants who report to clinic outside of injection window. 
The target visit windows for all visits, including injection visits, are outlined in the SSP Manual. In 
brief, the target visit window for all injection visits is +/- 3 days.Visits conducted outside of the target 
visit windows are allowable without restriction and are also defined in the SSP Manual for scheduling 
guidance. Each study visit, including the injection visit, should ideally be conducted within the target 
date range. When that is not possible, visits outside of the target dates may be completed.  
5.10 
Procedures for Injectable Dosing 
Refer to Appendix VI, Toxicity Management, for general toxicity management, as well as specific 
clinical and laboratory toxicity management guidelines, including directions regarding temporary and 
permanent study product holds.        


 
HPTN 083-01, FINAL V3.0 
46 of 152 
2 July 2021 
5.11 
Participants with Suspected or Confirmed HIV Infection at Screening, Enrollment,  
 
 
or Follow-Up 
All participants with preliminary positive HIV test results at screening or throughout the study will be 
actively linked with care and treatment from their choice of primary HIV service provider. Each of the 
clinical study sites have adolescent-friendly HIV care clinics available. 
5.11.1 Screening and Enrollment 
HIV testing will be performed to identify participants with HIV infection. Individuals who have one or 
more reactive or positive HIV tests at Screening or Enrollment are not eligible to participate in this 
study. Furthermore, at Screening and Enrollment individuals with any signs or symptoms consistent 
with acute (pre-seroconversion) HIV infection will not be enrolled, unless acute HIV infection is ruled 
out with appropriate laboratory testing, in consultation with the CMC. Signs and symptoms consistent 
with acute HIV infection are included in the SSP Manual.   
5.11.2 After Study Enrollment 
Frequent testing for HIV acquisition during the study period (at all study visits specified in the schedules 
of evaluation) will help prevent dosing with the study product in a participant who may have acquired 
HIV infection, minimizing the risk that resistant virus will emerge. HIV testing will also be performed 
using an RNA test that, in the opinion of the IoR or designee, is able to detect early HIV infection. 
Whenever possible, an assay that is US FDA-cleared for early HIV diagnosis, such as the Aptima HIV-1 
RNA Qualitative Assay, should be used.   
HIV acquisition after study enrollment must be confirmed in all cases using two independent samples 
collected on different days.   
Participants who have any reactive or positive HIV test result during follow-up visits will have further 
testing to confirm infection, as described in the SSP Manual and Appendix V. Study product will be 
withheld while this further testing is performed. 
Additional samples from participants with confirmed HIV infection may be sent to a local laboratory for 
resistance testing to assist with clinical management (results from resistance testing performed in local 
laboratories should not be reported to the HPTN SDMC or the HPTN LC). If a participant has a reactive 
or positive HIV test, the participant will not receive additional doses of study products pending further 
direction regarding testing and continued participation in the study from designated study team 
members, including the HPTN LC and the CMC. Refer to the SSP Manual for further information. 
Step 1 – Oral Phase 
Participants with confirmed HIV infection prior to receipt of their first injection will have oral study 
product permanently discontinued and will be transitioned to local HIV-related care and terminated from 
the study.  
Step 2 – Injection Phase 
Participants with confirmed HIV infection during Step 2 will not receive additional injections and will 
be followed per the SOE in Appendix V quarterly for approximately 48 weeks. In addition, sites will 
have a standard operating procedure (SOP) that outlines a plan in the event that a participant becomes 


 
HPTN 083-01, FINAL V3.0 
47 of 152 
2 July 2021 
HIV-infected during any Step of the study, and in particular during Step 2 of the study, which must 
include the participant’s facilitation into locally-available ART to be started immediately, to prevent 
emergence of drug resistance. Participants who seroconvert will be referred for care; sites will not be 
responsible for the actual provision/payment of ART.  Neither ART nor funds for provision of ART will 
be provided by the study. 
Step 3 – Follow-up Phase 
Participants with confirmed HIV infection during Step 3 will not receive oral Tenofovir/Emtricitabine 
(Trade name: TDF/FTC, Truvada®) or CAB LA and will be followed per the SOE in Appendix V 
quarterly through study exit (following an initial +8 Week Visit). In addition, sites will have a standard 
operating procedure (SOP) that outlines a plan to facilitate immediate initiation of non-study ART and 
link with appropriate HIV services in the event that a participant becomes HIV-infected during any Step 
of the study, and in particular during Step 2 of the study, to prevent emergence of drug resistance. 
Participants who seroconvert will be referred for care; sites will not be responsible for the actual 
provision/payment of ART. Neither ART nor funds for provision of ART will be provided by the study. 
5.12 
STIs 
Testing for Neisseria gonorrhoeae (GC)/Chlamydia trachomatis (CT), and syphilis will occur 
throughout the study. Testing will be performed at local laboratories. Symptomatic screening for STIs 
beyond what is required by the protocol will be at a site’s discretion. Participants will be referred for 
treatment of STIs as per local standard of care.   
5.13 
HBV and HCV 
Testing for HBV and HCV will be performed at Screening (HBsAg). Persons positive for HBsAg will 
not be enrolled in the study and will be referred to their primary provider for management. Participants 
will be tested for Hepatitis B surface antibody (HBsAb), and Hepatitis B core antibody (HBcAb, total) at 
Screening or Enrollment. Participants who do not have evidence of immunity to HBV (e.g., negative 
HBsAb) will be provided HBV vaccination, starting ideally at week 2. For participants who do not have 
evidence of HBV immunity at Enrollment, HBV testing should be repeated at the discretion of the IoR 
or designee during the study if clinically indicated, if the participant has elevated AST/ALT results 
(elevated level at discretion of IoR or designee), or if the participant expresses a concern about having 
acquired HBV infection after enrollment. Refer to the SSP Manual for persons who have a positive 
result for HBcAb (total) only. For participants who are negative for HBsAb at enrollment, HBsAb and 
HBcAb (total) will be checked at the end of the study.     
HCV antibody testing will be performed at Screening (see Appendix I). Those who are HCV antibody 
positive will be referred to their primary provider for management. For participants who do not have 
HCV antibody at Enrollment, HCV antibody testing should be repeated at the discretion of the IoR or 
designee during the study if clinically indicated, if the participant has elevated AST/ALT results 
(elevated level at discretion of IoR or designee), or if the participant expresses a concern about having 
acquired HCV infection after enrollment. HCV antibody testing will be repeated in all participants at the 
end of the study. Incident HCV infection during follow-up will not mandate discontinuation of study 
product absent other requirements per Appendix VI - Toxicity Management.       


 
HPTN 083-01, FINAL V3.0 
48 of 152 
2 July 2021 
5.14 
Behavioral and Acceptability Assessments 
Behavioral assessment questions have been previously used either in adolescent biomedical prevention 
trials or in the Phase III adult trials of cabotegravir. Behavioral assessment areas include sexual risk 
behavior, substance use, study product adherence and stigma associated with HIV and prevention 
technologies. 
Acceptability assessments of CAB LA will be administered via brief behavioral surveys.  The surveys 
will include, but not be limited to, questions about participants’ attitudes/beliefs towards CAB LA as 
well as product and study-related motivations. All measures will be programmed into CASI. 
5.15 
Interim Contacts and Visits 
Interim contacts and visits (those between regularly scheduled follow up visits) may be performed at 
participant request or as deemed necessary by the investigator or designee at any time during the study.  
Some interim visits may occur for administrative reasons. For example, the participant may have 
questions for study staff. Interim visits at which no data are collected are not documented on CRFs. 
Other interim contacts and visits may occur in response to AEs experienced by study participants. When 
interim contacts or visits are completed in response to participant reports of AEs, study staff will assess 
the reported event clinically, record the event on the CRF, and provide or refer the participant to 
appropriate medical care.   
5.16 
Criteria for Early Termination of Study Participation 
Participants may voluntarily withdraw from the study for any reason at any time (or their 
parents/guardians may, if they are under the legal age of consent). In general, for participants who 
withdraw consent from the study prematurely during a study visit, the requirements for that visit should 
be completed to the extent possible except for provision of study product and will be considered their 
final visit. When possible, a plan should be made to provide final laboratory results to the participant. 
For participants who inform the site in between visits that they wish to withdraw consent from the study, 
sites should make every effort to have the participant return any unused study product. Study staff will 
record the reason(s) for all withdrawals in participants’ study records and consult procedures for early 
discontinuation.  
Site IoRs may, with the agreement of the CMC, Protocol Chairs, DAIDS MO, and study statistician, 
withdraw participants before their scheduled termination visit to protect their safety, the safety of the 
staff, and/or if participants are unable or unwilling to comply with study procedures. Participants also 
may be withdrawn if the study sponsors, government or regulatory authorities (including the OHRP and 
US FDA), or site IRBs/ECs or ViiV terminate the study prior to its planned end date.  
6.0 
SAFETY MONITORING AND AE REPORTING 
6.1 AE Definition and Reporting 
An AE is defined as any untoward medical occurrence in a clinical research participant administered an 
investigational product and which does not necessarily have a causal relationship with the 
investigational product. As such, an AE can be an unfavorable or unintended sign (including an 


 
HPTN 083-01, FINAL V3.0 
49 of 152 
2 July 2021 
abnormal laboratory finding, for example), symptom or disease temporally associated with the use of an 
investigational product, whether or not considered related to the product. 
Study participants will be provided a 24-hour telephone number and contact information and instructed 
to contact the study clinician to report any AEs they may experience. For life-threatening events, they 
will also be instructed to seek immediate emergency care. Where feasible and medically appropriate, 
participants will be encouraged to seek evaluation where the study clinician is based, and to request that 
the clinician be contacted upon their arrival. With appropriate permission of the participant, whenever 
possible, records from all non-study medical providers related to AEs will be obtained and required data 
elements will be recorded on study CRFs. All participants reporting an AE will be followed clinically, 
until the AE resolves (returns to baseline) or stabilizes. 
Study site staff will document in source documents and the appropriate CRF all AEs [Grade 1 and 
higher, and any AE that leads to a study product hold (temporary or permanent) will be captured on 
CRFs] reported by or observed in enrolled study participants, regardless of severity and presumed 
relationship to study product. AE severity will be graded per the DAIDS Table for Grading Adult and 
Pediatric Adverse Events, Corrected Version 2.1, July 2017. This version will be used for the entire 
duration of the study. 
The AE reporting period for this study is from Enrollment (Week 0) until follow-up in the study ends. 
Relatedness is an assessment made by a study clinician of whether or not the event is related to the study 
agent. The relationship of all AEs to study product will be assessed as specified in Version 2.0, January 
2010 of the DAIDS EAE Reporting Manual.   
The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected 
Version 2.1, July 2017, will be used for the entire duration of the study for determining and reporting the 
severity of AEs. The DAIDS grading table is available on the DAIDS RSC website at 
https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables.  
6.2 EAE Reporting 
After the protocol-defined AE reporting period, unless otherwise noted, only SUSARs as defined in 
Version 2.0 of the EAE Manual will be reported to DAIDS if the study staff become aware of the events 
on a passive basis (from publicly available information). 
Requirements, definitions, and methods for expedited reporting of AEs are outlined in Version 2.0 of the 
DAIDS EAE Manual, which is available at https://rsc.niaid.nih.gov/clinical-research-sites/manual-
expedited-reporting-adverse-events-daids.  
The study agents for the purposes of EAE reporting are: Oral CAB 30 mg oral tablet; CAB LA 3 mL 
(600 mg) intramuscular (IM) injectable suspension.  
6.2.1 Reporting to DAIDS 
The DAIDS Adverse Event Reporting System (DAERS), an internet-based reporting system, must be 
used for EAE reporting to DAIDS. In the event of system outages or technical difficulties, EAEs may be 


 
HPTN 083-01, FINAL V3.0 
50 of 152 
2 July 2021 
submitted via the DAIDS EAE form. For questions about DAERS, please contact 
CRMSSupport@niaid.nih.gov. Site queries may also be sent with the DAERS application itself. 
If the DAERS website or site internet is non-functional, sites will submit expedited AEs by documenting 
the information on the current DAIDS EAE form. This form is available on the DAIDS RSC website: 
https://rsc.niaid.nih.gov/clinical-research-sites/paper-eae-reporting. For questions about EAE reporting, 
please contact the DAIDS RSC at DAIDSRSCSafetyOffice@tech-res.com. 
6.2.2 Reporting Requirements for This Study 
The SAE Reporting Category, as defined in Version 2.0 of the DAIDS EAE manual, will be used for 
this study (the definition of an SAE is also included in the manual).   
In addition to SAEs, sites will report in an expedited manner the following results:   
• ALT ≥ 3xULN AND total bilirubin ≥ 2xULN (must be both in order to require expedited reporting) 
• Any seizure event 
These reporting requirements are for each study participant from Enrollment (Week 0) until follow-up in 
the study ends. After this time, sites must report serious, unexpected, clinical suspected adverse drug 
reactions if the study site becomes aware of the event on a passive basis, i.e., from publicly available 
information. 
The study agents for the purposes of EAE reporting are: Oral CAB 30 mg oral tablet; CAB LA 
injectable suspension (200 mg/mL).  
In addition to submitting EAE information to the DAIDS Safety Office via DAERS, the site investigator 
may be required to submit AE and EAE information to local regulatory agencies or other local 
authorities. 
Information on Grade 1 and higher AEs will be included in reports to the US FDA, and other 
government and regulatory authorities as applicable. Site staff will report information regarding AEs to 
their IRB in accordance with all applicable regulations and local IRB requirements. 
6.3 Safety Monitoring 
Two hundred and thirty (n=230) healthy participants from completed studies have received single or 
repeat doses of CAB LA in Phase 1 studies at doses ranging from 100-800 mg administered as single or 
split IM or SC injections. In the Phase 1 program, to date there have been no drug-related Grade 3 or 
Grade 4 clinical AEs and only one participant has been withdrawn from dosing due to mild and transient 
rash. Injection site reactions (ISR) occurred in the majority of participants following IM (77% with any 
ISR) dosing, however, the reactions were mild and moderate (overall ISR Grade 2: 14% in IM without 
any Grade 3 or 4 ISRs).32 ISRs related to CAB LA injection were common but generally mild (IM: 86%, 
SC: 99%) with no Grade 3 ISR AEs in Phase 1 studies. The most frequent ISRs for IM dosing were pain 
(71%), erythema (9%) and nodules (7%).  Median IM ISR durations were approximately 5 days for pain 
and erythema, and approximately 22 days for nodules.32 


 
HPTN 083-01, FINAL V3.0 
51 of 152 
2 July 2021 
AEs were reported at all studied doses. The most frequent (>5%) non-ISR AEs were headache (overall 
rate of 16%: 10% in oral and 27% in LA) which occurred more frequently than in placebo subjects 
(11%) and upper respiratory tract infection (overall rate of 6%: 2% in oral and 12% in LA) versus none 
in placebo subjects. CAB was well tolerated across all studies with an overall incidence of 13% of any 
drug-related AEs and few drug related withdrawals. 
The ECLAIR study, conducted at 10 US sites, screened 205 individuals in order to enroll and randomize 
127 HIV-uninfected low-risk men. Participants received daily oral CAB 30 mg or daily oral placebo in a 
randomized 5:1 ratio during the 4-week oral lead-in phase.35 One participant randomized to active study 
product (oral CAB and CAB LA) withdrew prior to the oral lead-in due to being incarcerated. During 
the oral lead-in, 11 participants withdrew prior to their first injection, all of whom were randomized to 
CAB LA, seven for AEs and four for other reasons. Ninety-four (94) participants received at least one 
injection of CAB LA 800 mg and 21 participants received at least one injection of placebo. Of those that 
started injections 95% (20 of 21) of those randomized to placebo and 93% (87 of 94) of those 
randomized to CAB LA completed all three injections. The participant in the placebo arm who did not 
complete all three injections reached a protocol-defined stopping criteria (he acquired HIV infection 
after his second injection). Four participants on the CAB LA arm withdrew after their second injection, 
citing injection tolerability as a primary reason. Three other participants discontinued study participation 
after receiving injections for non-AE and non-injection-related reasons. 
Fifteen participants experienced a Grade 1 or higher ALT and 14 experienced a Grade 1 or higher AST. 
There were no Grade 3 or 4 ALT elevations. AE events leading to withdrawal included transient 
neutropenia (three participants), transiently elevated CPK (three participants), and fatigue (one 
participant). Two SAEs were reported, one deep vein thrombosis on placebo that was considered 
possibly drug-related and one appendicitis on CAB LA that was not considered drug related. Eighteen 
participants reported Grade 3 ISR pain.  
Grade 4 treatment emergent CPK elevations with concomitant AST and/or ALT elevations were noted 
in four participants at the Week 4 visit, leading to early withdrawal in three participants.   One of the 
four participants described a new rigorous exercise regimen prior to the Week 4 study visit; a second of 
these events resolved despite ongoing exposure to study product. All four Grade 4 abnormalities were 
resolving at one-week follow-up visits and have subsequently returned to normal off study product.  
Close cooperation between the Protocol Chair, study site Investigator(s), DAIDS Medical Officer, LOC 
Clinical Research Manager, SDMC Biostatistician, SDMC Clinical Affairs Staff, HPTN LC, and other 
study team members will be necessary in order to monitor participant safety and to respond to 
occurrences of toxicity in a timely manner.  
The study site Investigators are responsible for continuous close monitoring and management of AEs. 
Sites are required to have detailed SOPs describing methods for AE reporting and toxicity management 
to ensure that AEs are reported and managed in accordance with the protocol and for alerting the CMC 
(outlined below) if unexpected concerns arise. 
A sub-group of the Protocol Team, including the Protocol Chair and Co-Chair, DAIDS Medical Officer, 
and other site investigators will serve as members of the CMC. The CMC provides support to sites 
regarding individual participant clinical management (e.g., questions related to eligibility, toxicity 
management, clinical holds of study drug, etc.).  


 
HPTN 083-01, FINAL V3.0 
52 of 152 
2 July 2021 
6.4 Clinical Data Review 
A multi-tiered safety review process will be followed for the duration of this study. The study site 
investigators are responsible for the initial evaluation and reporting of safety information at the 
participant level, and for alerting the CMC if unexpected concerns arise.   
Participant safety data is also monitored by the SDMC Clinical Affairs staff who review incoming safety 
data for completeness and consistency on an ongoing basis. Events identified as questionable, 
inconsistent, or unexplained will be queried for verification.  
AE reports submitted in an expedited manner to the DAIDS Safety Office will be forwarded to the 
DAIDS Medical Officer for review and possible reporting to the FDA as a Safety Report. 
This study will be monitored by a NIAID Data and Safety Monitoring Board (DSMB), along with the 
parent protocols, which will meet at least annually to review safety and efficacy data. More frequent or 
ad hoc reviews of safety data may be conducted by the DSMB as needed.  
6.5 Social Harms and Social Benefits Reporting 
It is possible that participants' involvement in the study could become known to others, and that a social 
harm may result (i.e., because participants could be perceived as being HIV-infected or at "high risk" for 
HIV infection). For example, participants could be treated unfairly, or could have problems being 
accepted by their families and/or communities. These are social harm events. Social harms events are 
those negative events that a participant reports as affecting them as a result of being involved in a 
research study, not the researcher’s opinion of how they perceive an event has affected a participant. A 
social harm that is reported by the participant and judged by the IoR/designee to be serious or 
unexpected will be reported to the responsible site’s IRBs at least annually, or according to their 
individual requirements.   
Social harms and benefits will be collected and reported on CRFs during regular visits. In the event that 
a participant reports a social harm, every effort will be made by study staff to provide appropriate care 
and counseling to the participant as necessary, and/or referral to appropriate resources for the safety of 
the participant. Each site will provide such care and counseling in accordance with standardized 
guidance in the SSP Manual. While maintaining participant confidentiality, study sites may engage their 
Community Advisory Board in exploring the social context surrounding instances of social harms, to 
minimize the potential occurrence of such an impact. In addition to social harms, any benefits of study 
participation, which are outcomes reported by the participant as a benefit to them as a result of being in 
the study (e.g., improvement in relationships), will also be collected and reported into the database. 
 
7.0 
STATISTICAL CONSIDERATIONS 
7.1 Review of Study Design 
This is a single arm, open label, safety, tolerability, and acceptability study of CAB LA for prevention of 
HIV-acquisition in sexually-active, HIV-uninfected adolescents (below aged 18 years old at time of 
enrollment).  


 
HPTN 083-01, FINAL V3.0 
53 of 152 
2 July 2021 
The study includes a 5-week oral CAB 30mg QD safety lead-in followed by a series of 5 intramuscular 
(IM) injections of 3 mL (600 mg) CAB LA administered at 8-week intervals after a 4-week loading dose 
(injections at weeks 5, 9, 17, 25 & 33). Follow up on study product (oral and injectable) will occur for 
34 weeks. All participants who have received at least one injection will be followed for 48 weeks after 
their last injection. Waning levels of cabotegravir (the PK tail) will be covered with locally sourced oral 
Tenofovir/Emtricitabine (TRADE NAME: TDF/FTC, TRUVADA®) for daily use or continued use of 
CAB LA for 48 weeks.  
The sample size for this study will be set to enroll approximately 50 participants. The sample size for 
this protocol (n=50) is the number of participants agreed upon by the industry sponsor and regulators in 
order to provide supplementary safety and behavioral data on adolescents in collaboration with the 
HPTN 083 and HPTN 084 adult trials. The primary aims of the study are focused on safety, tolerability, 
and acceptability of this long-acting product.  
Finally, in-depth qualitative interviews will be conducted with 10 participants (total, across all sites) 
after Week 34 to explore issues of acceptability and preference for oral tablets and/or injections. 
Additionally, up to 10 parents/guardians of participants (total, across all sites) will be asked to 
participate in in-depth interviews to explore facilitators and barriers to adolescent enrollment in 
biomedical clinical trials.  
7.2 Endpoints 
7.2.1 Primary Endpoints 
• Safety endpoint: Proportion of participants experiencing any Grade 2 or higher clinical adverse 
events (AEs) and laboratory abnormalities among participants who receive at least one injection of 
CAB LA 
• Tolerability endpoint: Proportion of participants who receive at least 1 injection and who discontinue 
receiving injections prior to the full course of injections due to intolerability of injection, frequency 
of injections or burden of study procedures 
• Acceptability endpoint: Proportion of participants who complete all scheduled injections and 
proportion of participants who receive at least one injection whom would consider using CAB LA 
for HIV prevention in the future 
7.2.2 Secondary Endpoints 
• Plasma CAB pharmacokinetics 
• Proportion of participants experiencing Grade 2 or higher clinical AEs and laboratory abnormalities 
in the oral phase and the aggregate over the entire study period   
• Proportion of injection visits that occurred “on-time”  
• Change from enrollment of self-reported sexual behavior (number of sexual partners, increased 
episodes of unprotected anal intercourse) during the study period  


 
HPTN 083-01, FINAL V3.0 
54 of 152 
2 July 2021 
7.3 Sample Size  
The sample size for this protocol (n=50) is the number of participants agreed upon by the industry 
sponsor and regulators in order to provide supplementary safety and behavioral data on adolescents in 
collaboration with the HPTN 083 and HPTN 084 adult trials. The goal of the safety evaluation for this 
study is to identify safety concerns associated with CAB LA. 
Since each of the primary endpoints is a proportion, Table S1 shows the precision (confidence interval 
width) that will be obtained for each endpoint with a sample size of 50. 
Table S1. Width of 95% confidence interval for estimated proportion as a function of the true 
proportion, assuming a sample size of 50. 
True proportion 
Width of 95% CI 
0.1 
± 0.083 
0.2 
± 0.11 
0.3 
± 0.13 
0.4 
± 0.14 
0.5 
± 0.14 
The study will recruit sufficient participants to ensure that at least 50 participants progress to the 
injection phase. 
7.4 Randomization 
There is no treatment randomization due to this study being a single arm, open label trial. 
7.5 Blinding 
Participants and site staff will be unblinded throughout the trial. 
7.6 Data and Safety Monitoring Analysis 
7.6.1 Study Monitoring Committee  
NIAID DSMB oversight is planned for this study. Monitoring guidance will be detailed in a separate 
Interim Monitoring Plan.  
In addition, approximately every six months the HPTN SMC will conduct interim reviews of study 
progress, including rates of participant accrual, visit retention, and completion of primary and main 
secondary endpoint collection. The frequency and content of SMC reviews will be determined prior to 
the start of the study as outlined in the HPTN Manual of Procedures (MOP).  


 
HPTN 083-01, FINAL V3.0 
55 of 152 
2 July 2021 
7.7 Primary Analyses 
All participants who receive at least one injection will contribute to the primary analyses. When the use 
of descriptive statistics to assess group characteristics or differences is required, the following methods 
will be used: for categorical variables, the number and percent in each category; for continuous 
variables, the mean, median, standard deviation, quartiles and range (minimum, maximum).  
7.7.1 Safety Endpoints 
The primary safety analysis will include Grade 2 or higher clinical and laboratory events that occur from 
the initial injection to 48 weeks after the last injection among participants who receive at least one 
injection.  
To assess safety, the number and the percent of participants experiencing each safety endpoint will be 
tabulated. Each participant will contribute once in each category (for example, only for the highest 
severity AE for each participant) for the calculation of event rates. Exact binomial confidence intervals 
will be calculated for each safety endpoint.   
7.7.2 Injection Site Reaction (ISR)  
The number and percentage of participants experiencing each type of injection site reaction sign or 
symptom will be tabulated by severity. For a given sign or symptom, each participant’s ISR will be 
counted once under the maximum severity for all injection visits as well as by each successive injection. 
In addition, we will report the proportion of injections (over all participants) that resulted in an ISR. A 
95% CI (using a robust variance) will be computed. 
7.7.3 AEs and Serious Adverse Events (SAEs) 
AEs will be tabulated using MedDRA preferred terms. The number and percentage of participants 
experiencing each specific AE (All AEs, Grade 2 or higher, and SAEs) will be tabulated by severity and 
by relationship to study product. For the calculations in these tables, each participant’s AEs will be 
counted once as the maximum severity and relationship to study product. AEs leading to temporarily or 
permanently stopping drug will also be summarized. AEs will be summarized for those that are 
treatment emergent during LA dosing.  
A listing of EAEs reported to the DAIDS RSC Safety Office will provide details of the events including 
severity, relationship to study product, time between onset and last injection, number of injections 
received, and a summary of the event. 
7.7.4 Tolerability 
To assess tolerability, the number and the percent of participants who receive at least one injection and 
discontinue receiving injections prior to the full course due to intolerability of injection (including but 
not limited to ISR), frequency of injections, or burden of procedures or any AE will be tabulated. 


 
HPTN 083-01, FINAL V3.0 
56 of 152 
2 July 2021 
7.7.5 Acceptability 
To assess acceptability, the number and percentage of participants who complete all scheduled injections 
will be described. Additionally, the number and the percent of participants who receive at least one 
injection that would consider using CAB LA for HIV prevention in the future will be tabulated. 
Acceptability will be assessed by age and in aggregate.  
Acceptability of CAB LA will also be assessed through administration of brief behavioral surveys and 
qualitative interviews.  The surveys will include, but not be limited to, questions about participants’ 
attitudes/beliefs towards CAB LA; product and study-related motivations. In addition, a subset of 
participants will be invited to take part in qualitative assessments of acceptability in order to provide 
more holistic and contextualized information on motivations, attitudes and experiences using injectable 
PrEP, reasons for and circumstances related to product and/or study discontinuation, and future 
intentions related to PrEP use. 
A subset of 10 willing participants will complete an in-depth interview (IDI) to be scheduled after the 
Week 34 visit. In addition, up to 10 parents of participants will be invited to participate in in-depth 
interviews that will explore facilitators and barriers to adolescent participation in biomedical HIV 
prevention trials. When conducting a qualitative exploration, the sampling method should be designed to 
include a range of possible perspectives on the phenomenon under study, thus ideal qualitative samples 
are purposive in nature. For this study, we will utilize a purposive sampling strategy, which will allow 
for consideration of the concepts of range, saturation/redundancy, and stratification in the sampling 
frame. We will ask sites to identify potential participants as well as parents/caregivers who would be 
interested in and comfortable with sharing their experiences with the study product as well as study 
procedures. Data on acceptability and factors affecting adherence will be collected during the IDI, 
including questions that explore the use and the acceptability of both the oral and injectable CAB, along 
with examination of preference for pills or injections. Additional interview topics will include 
challenges to study participation as well as product use. We will also discuss with participants the 
acceptability of parental involvement in the consent process.  
These interviews will be conducted by a trained study interviewer and will follow a semi-structured 
questionnaire guide. They will be approximately 30-60 minutes in duration and will be conducted in an 
area that maximizes participant privacy and confidentiality. Participants may be compensated for the 
completion of the in-depth interview. These interviews will be recorded for analysis and transcribed, and 
the recordings will be destroyed once all analyses are complete. 
 
7.7.6 Local Laboratory Values  
Box plots of local laboratory values will be generated for baseline values and for values measured 
during the course of the study by visit. Each box plot will show the first quartile, the median, and the 
third quartile. Outliers will also be plotted. If appropriate, horizontal lines representing boundaries for 
abnormal values will be plotted.  
The number (percentage) of participants with local laboratory values recorded as meeting Grade 2 AE 
criteria or above as specified in the DAIDS AE Grading Table will be tabulated for follow-up time 
points. Reportable clinical laboratory abnormalities without an associated clinical diagnosis will also be 
included in the tabulation of AEs described above. 


 
HPTN 083-01, FINAL V3.0 
57 of 152 
2 July 2021 
7.8 Secondary Analyses 
7.8.1 Plasma Drug-Level Concentrations  
Descriptive analyses of plasma concentration of CAB LA will be performed using mean, median, 
standard deviation, coefficient of variation (%CV) and range, for example. Graphical displays of the 
data based on appropriate techniques (e.g., boxplots, histograms, kernel density estimates, probability 
plots, scatterplots) will be generated to visually explore distributional properties of the data. Statistics 
and graphical displays will be produced for plasma concentrations within and across timepoints. In 
addition, proportion of participants with plasma CAB concentrations <LLQ, between LLQ and PA-
IC90, 1-4X PA-IC90, and >4X PA-IC90 will be calculated at pre-specified time points after the final 
injection. In addition to concentration summaries, parameters may be derived by non-compartmental 
pharmacokinetic methods.   
7.8.2 Safety Endpoints 
Secondary safety analyses will be summarized using the same method described in section 7.7.1, applied 
over the oral phase only (week 0 to week 4) and the aggregate oral+injectable+follow-up period. 
7.8.3 AEs and Serious Adverse Events (SAEs) 
AEs and SAEs will be summarized using the same method described in section 7.7.3, applied over the 
oral phase only (week 0 to week 4) and the aggregate oral+injectable+follow-up period. 
7.8.4 Injection adherence  
The number and the percent of injection visits that occur within the injection visit window will be 
tabulated.  
7.8.5 Sexual Risk Behaviors 
Change in sexual risk behavior (number of sexual partners, episodes of unprotected anal and/or vaginal 
intercourse) during the injection phase will be measured by summarizing the change from baseline by 
visit.  
7.9 Qualitative Analysis  
All qualitative interviews will be conducted by trained interviewers, digitally-recorded, transcribed and 
translated into English (as needed), and then uploaded into a qualitative software analysis program (such 
as NVivo 12.) The protocol chair and her team will follow a process of reading, coding, data display and 
data reduction in order to explore in greater depth participants’ attitudes towards and experiences with 
the product. Data coding and analysis will be both iterative and interactive processes. The team will first 
read all interview transcripts in order to increase familiarity with the data. Next, the team will assign a 
priori codes and create emergent codes. Transcripts will then be re-read to create pattern codes that 
connect subsequent concepts under larger headings. Consistent patterns in meaning, concepts, and 
themes across all interviews will be identified, and detailed memos/data matrices will be developed to 
examine how participants’ perceptions related to product use (i.e., ease of use, perceived efficacy, side 
effects) and to trial participation (i.e., motivations for participation, interactions with trial staff, impact 


 
HPTN 083-01, FINAL V3.0 
58 of 152 
2 July 2021 
on partner, parent or other social relationships) influence acceptability and interest in future use of an 
injectable PrEP product. Comparative analyses will be conducted to clarify differences that may exist 
for any subgroups of adolescents. Coding and analytic activities will be discussed during qualitative data 
analysis meetings, and discrepancies in coding and interpretation will be resolved through consensus. A 
similar analytic approach will be followed for parent/guardian interviews. All recordings will be 
destroyed, once all analyses are complete. 
8.0 
HUMAN SUBJECTS CONSIDERATIONS 
8.1 Ethical Review 
This protocol and the template informed consent/assent forms contained in the appendices will be 
reviewed and approved by the HPTN Scientific Review Committee (SRC) and DAIDS Prevention 
Science Review Committee (PSRC) with respect to scientific content and compliance with applicable 
research and human subjects regulations.  
The protocol, site-specific informed consent form, participant education and recruitment materials, and 
other requested documents — and any subsequent modifications — also will be reviewed and approved 
by the ethical review bodies responsible for oversight of research conducted at the study site.  
Subsequent to initial review and approval, the responsible IRBs/ECs will review the protocol at least 
annually. The Investigator will make safety and progress reports to the IRBs/ECs at least annually, and 
within three months of study termination or completion. These reports will include the total number of 
participants enrolled in the study, the number of participants who completed the study, all changes in the 
research activity, and must comply with the requirements of 45 CFR 46.108(a)(4) and 21 CFR 56.108b 
for promptly reporting the following: all unanticipated problems involving risks to human subjects or 
others; serious or continuing noncompliance with applicable regulations or the requirements or 
determinations of their IRBs/ECs; and any suspension of termination of IRB approval. Study sites are 
responsible for the submission of continuing review to the DAIDS Protocol Registration Office (PRO), 
in accordance with the current DAIDS Protocol Registration Policy and Procedure Manual. 
8.2 Informed Consent 
This section provides details regarding informed consent and assent requirements and procedures for 
adolescents. Site investigators and their designees will be required to determine participant age and 
ability to provide independent informed consent for study participation consistent with IRB/EC policies 
and procedures. Each site must establish SOPs, roles, and responsibilities for completing these 
determinations, and study staff involved in completing these determinations must have documented 
training in the relevant policies and procedures prior to initiating study activity.  
Written informed consent and written assent will be obtained for study participation as follows:  
• If the potential participant is of legal age or otherwise able to provide independent informed consent 
as determined by site SOPs, local laws and regulations, and consistent with site IRB/EC policies and 
procedures: The potential participant must provide written informed consent for study participation.  
• If the potential participant is not of legal age to provide independent informed consent as 
determined by site SOPs and local laws and regulations: Parent, legal guardian, or other legally 


 
HPTN 083-01, FINAL V3.0 
59 of 152 
2 July 2021 
authorized representative must provide written informed permission for study participation and the 
potential participant must provide written assent for study participation.  
Note: IRB/EC risk determinations will guide whether the consent of one or both parents may be required 
for this study. All IRB/EC requirements must be followed.  
• During study follow-up, if such a participant reaches the legal age and is able to provide 
independent informed consent as determined by site SOPs: The participant must then provide written 
informed consent to continue study participation. 
Written informed consent and assent (as applicable) for participation will be obtained before any study-
specific procedures are performed. The informed consent process will include information exchange, 
detailed discussion, and formal assessment of understanding of all required elements of informed 
consent, including the potential risks, benefits, and alternatives to study participation. The process will 
describe what is known about the safety and tolerability of the study products and participants and 
parents/guardians will be extensively counseled on the importance of adherence to the study product 
regimen and study visit schedule. The approach adopted by the site will be tailored to adolescents, 
utilizing a variety of supporting materials, and may be spread over multiple sessions to foster sufficient 
understanding of the study prior to making the decision to take part.   
Appendices VII-IX provide sample informed consent/assent forms for obtaining parent or legal guardian 
permission and adolescent assent for study participation. Appendices X-XIII provide sample informed 
consent/assent forms for adolescent qualitative interviews and parent/legal guardian interviews. 
Appendices XIV-XVI provide sample informed consent/assent forms for specimen storage and future 
use. All sample informed consent and assent forms may be modified by sites to meet IRB/EC 
requirements. If the participant, parent, or guardian (as applicable) is unable to read, the process for 
consenting illiterate participants, as defined or approved by the IRB/EC, should be followed.  
As indicated above, parental consenting requirements at each site will depend on the IRB/EC risk 
determination and all IRB/EC requirements will be followed.  
In general, each participant is expected to take part in the informed consent process and with his or her 
parent or legal guardian, if appropriate, and both the assent of the participant and the permission of the 
parent or legal guardian will be required for all consent decisions, if the participant does not self-
consent.  
Should the consenting parent (or guardian) of a participant no longer be available for any reason, sites 
should follow the guidelines and procedures described by their IRBs/ECs. Study sites may continue to 
provide care for the participant as needed and appropriate (outside of the study), consistent with local 
standard of care.  
Participants may also reach the legal age of consent during follow-up. In this case, written informed 
consent for continued participation will be obtained from participants once they reach legal age at their 
next study visit. If participants do not consent for continued study participation, they should be 
discontinued from the study.  
Each study site is responsible for developing study informed consent forms for local use that describes 
the purpose of the study, the procedures to be followed, and the risks and benefits of participation, in 


 
HPTN 083-01, FINAL V3.0 
60 of 152 
2 July 2021 
accordance with all applicable regulations. If applicable, the study site also is responsible for translating 
the template form into local languages and verifying the accuracy of the translation by performing an 
independent back-translation. 
Participants will document their provision of informed consent and assent by signing their informed 
consent forms. All participants will be offered a copy of their informed consent form. 
8.3 Incentives 
Pending IRB approval, participants will be compensated for their time and effort in this study, and/or be 
reimbursed for travel to study visits and time away from work. This includes the time and effort of 
parents or legal guardians who bring their child to the study visits. Site-specific reimbursement amounts 
will be specified in the study informed consent forms. 
8.4 Confidentiality 
All study-related information will be stored securely at the study site. All participant information will be 
stored in locked file cabinets in areas with access limited to study staff. All laboratory specimens, 
reports, study data collection, process, and administrative forms will be identified by a coded number 
only to maintain participant confidentiality. All records that contain names or other personal identifiers, 
such as locator forms and informed consent forms, will be stored separately from study records 
identified by code number. All local databases will be secured with password-protected access systems. 
Forms, lists, logbooks, appointment books, and any other listings that link participant ID numbers to 
other identifying information will be stored in a separate, locked file in an area with limited access. 
Participant’s study information will not be released without the written permission of the participant, 
except as necessary for monitoring by the NIAID and/or its contractors; representatives of the HPTN 
LOC, HPTN SDMC, and/or HPTN LC; site IRBs/ECs; other local, US, or international regulatory 
authorities; (including the OHRP and US FDA); or ViiV.  
8.5 Communicable Disease and Statutory Rape Reporting Requirements 
Study staff will comply with all applicable local requirements to report communicable diseases 
identified among study participants to local health authorities and will comply with applicable state laws 
regarding the reporting requirements of sexual activity of minors that can be considered statutory rape. 
Participants will be made aware of all reporting requirements during the study informed consent process. 
8.6 Study Discontinuation 
The study also may be discontinued at any time by NIAID, the HPTN, the study sponsors, government 
or regulatory authorities (including the OHRP and US FDA), site IRBs/ECs or if appropriate, or ViiV. 
This would be done primarily due to safety concerns for the patients or due to an earlier-than-expected 
indication of product efficacy or study futility. 
9.0 
LABORATORY SPECIMENS AND BIOHAZARD CONTAINMENT 
Laboratory procedures are described below and in Appendices I to IV. Refer to Appendix V for any 
participant who has a reactive or positive HIV test after Enrollment. 


 
HPTN 083-01, FINAL V3.0 
61 of 152 
2 July 2021 
9.1 Local Laboratory Specimens 
The following types of tests will be performed at the local laboratory:  
• HIV testing (see SSP Manual) 
• HBV and HCV testing to include HBsAg, HBsAb, HBcAb, HCV antibody tests   
• Complete blood count (CBC) with differential  
• Chemistry testing (blood-urea nitrogen (BUN) or urea, creatinine, CPK, glucose, calcium, 
phosphorous, amylase, lipase) 
• LFTs (AST, ALT, TBili, alkaline phosphatase) 
• Fasting lipid profile (total cholesterol, high-density lipoprotein (HDL), triglycerides, low-density 
lipoprotein (LDL)) – calculated or measured  
• Syphilis serologic testing 
• Urine (protein and glucose) 
• Urine for GC/CT NAAT testing 
• Rectal swabs for GC/CT NAAT testing; 
• Oral pharyngeal swabs for GC/CT NAAT testing; 
• Plasma storage 
• DBS storage 
• HIV viral load (if HIV-infected) 
• CD4 cell count (if HIV-infected) 
• Real-time resistance testing for clinical management, if indicated and available (if HIV-infected) 
If the HIV testing algorithm includes HIV rapid testing, that testing may be performed in the clinic or 
laboratory.  
 
Each study site should adhere to standards of Good Clinical Laboratory Practice (GCLP), the HPTN 
Manual of Operations (MOP), the SSP Manual and local SOPs for proper collection, processing, 
labeling, transport, and storage of specimens to the local laboratory. Specimen collection, testing, and 
storage at the local laboratory will be documented using the HPTN Laboratory Data Management 
System (LDMS) as described in the SSP Manual. 
All specimens will be shipped in accordance with International Air Transport Association (IATA) 
specimen shipping regulations. All shipments will be documented using the HPTN LDMS as described 
in the SSP Manual.  
9.2 Stored Specimens 
Plasma will be stored at the local site throughout the study and afterwards, until discard approval is 
given by DIADS, the Principal Investigator (PI), and the HPTN LC. A subset of the stored samples will 


 
HPTN 083-01, FINAL V3.0 
62 of 152 
2 July 2021 
be shipped to the HPTN LC (located in the US) for Quality Assurance (QA) and other assessments. As 
indicated below, testing on stored samples will be performed by the HPTN LC or another laboratory 
designated by the HPTN LC. 
9.3 Virology 
The HPTN LC will perform QA testing, including testing to determine HIV infection status in selected 
cases. Additional assays may be performed at the HPTN LC or a laboratory designated by the HPTN 
LC. This testing may include the following tests for participants who acquire HIV infection: HIV viral 
load, HIV resistance testing, HIV subtyping, and other tests to characterize HIV viruses and/or the host 
response to HIV infection. Results will not be returned to the sites or study participants, with the 
exception of HIV diagnostic testing (if results obtained at the HPTN LC do not agree with site results).  
Resistance testing will be performed at the HPTN LC or a laboratory designated by the HPTN LC. This 
testing will be performed periodically during the study. Results of this testing will not be returned to 
study sites. Because real-time resistance testing may be needed for clinical management in the event of 
HIV infection, each site will have an SOP as to how they will accomplish real-time local or regional 
resistance testing to assist with clinical decision making; separate specimens should be collected for that 
testing.   
9.4 Pharmacology 
Blood samples will be collected throughout the study from all participants and assayed for plasma CAB 
concentrations.  PK sample times include predose trough samples at W5, W9, W17, W25, and W33, 
(final concentration in injection phase) and 1-week post injection samples at W6, W10, W18, W26, 
W34.  In addition, follow-up samples will be collected for 48 weeks(Appendix II and Appendix III or 
IV) and at HIV confirmatory visit (Appendix V).   
Plasma samples will be processed and frozen locally for subsequent shipment to the HPTN LC 
following procedures outlined in the SSP Manual. Pharmacology testing will be performed at the HPTN 
LC or at an outside laboratory designated by the HPTN LC. The primary pharmacologic assessments 
will be performed using assays that have been validated in accordance with regulatory requirements. 
Results will not be returned to the study participants or study sites. 
Plasma and DBS samples will be processed and frozen locally for subsequent shipment to the HPTN LC 
following procedures outlined in the SSP Manual. Pharmacology testing will be performed at the HPTN 
LC or at an outside laboratory designated by the HPTN LC. The primary pharmacologic assessments 
will be performed using assays that have been validated and approved by the Clinical Pharmacology 
Quality Assurance (CPQA) Committee (reference assay validation report). Results will not be returned 
to the study participants or study sites. Plasma and DBS will be collected in Step 3 and if a study 
participant seroconverts for potential pharmacologic analysis of plasma TFV and DBS TFV-DP 
concentrations, respectively, to assess PrEP adherence.   
Stored plasma may also be tested for the presence of other ARV drugs or other concomitant 
medications. 


 
HPTN 083-01, FINAL V3.0 
63 of 152 
2 July 2021 
9.5 Quality Control and Quality Assurance Procedures 
Study sites will document that their laboratories are certified under the Clinical Laboratory Improvement 
Amendments Act of 1988 (CLIA-certified) and/or participate in an External Quality Assurance (EQA) 
program. HPTN LC staff will conduct periodic visits to each site to assess the implementation of on-site 
laboratory quality control (QC) procedures, including proper maintenance of laboratory testing 
equipment and use of appropriate reagents. HPTN LC staff will follow up directly with site staff to 
resolve any QC or QA problems identified through proficiency testing and/or on-site assessments. 
9.6 QC for HIV Diagnostic Testing 
Local laboratories will perform testing for HIV diagnosis at Screening, Enrollment, and follow-up visits. 
Algorithms for HIV diagnostic testing are provided in the SSP Manual. 
Throughout the course of the study, the sites will ship an aliquot per visit per participant quarterly, per 
the SSP schedule. The HPTN LC with guidance from the SDMC will select a random sample of stored 
specimens to test for QA purposes. The total number of specimens undergoing QA testing will follow 
the QA processes as described in the HPTN MOP and at the discretion of the HPTN LC. 
The HPTN LC will test the specimens for evidence of HIV infection and compare the results of their 
tests with the results obtained by the local labs. HPTN LC staff will follow-up directly with site staff to 
resolve any QA problems identified through this process. 
9.7 Quality Assurance for General Laboratory Testing 
Local laboratories will perform hematology, chemistry, liver function, lipids, hepatitis, STI, CD4, RNA 
and urinalysis testing as indicated in each relevant SOE.  
9.8 Quality Assurance for CD4 Cell Count Testing 
Local laboratories may also perform CD4 cell count testing as indicated in Appendix II.  
9.9 Quality Assurance for HIV RNA Testing 
Local laboratories may also perform HIV RNA/viral load testing (platform and test kit approved by the 
HPTN LC) as indicated in Appendix II or for evaluation of possible acute HIV infection.  
9.10 
Specimen Storage and Possible Future Research Testing 
Study sites will store specimens collected in this study at least through the end of the study (completion 
of all study-related testing, including testing at the HPTN LC, which is typically one year post main 
paper publication). In addition, study participants will be asked to provide written informed consent for 
the collected samples to be stored after the end of the study, for possible future non-protocol listed 
testing. The specimens of participants who do not consent to long-term storage and additional testing 
will be collected and remain stored as planned, and then be destroyed after all of the protocol specified 
testing (including assessments at the HPTN LC) has been completed and approval from the protocol 
team and network leadership is provided. 


 
HPTN 083-01, FINAL V3.0 
64 of 152 
2 July 2021 
Samples from participants who did not successfully enroll in the study may be discarded once sample 
lists are provided by the HPTN LC in consultation with the HPTN SDMC. 
9.11 
Biohazard Containment 
As the transmission of HIV and other blood-borne pathogens can occur through contact with 
contaminated needles, blood, and blood products, appropriate blood and secretion precautions will be 
employed by all personnel in the drawing of blood and shipping and handling of all specimens for this 
study, as currently recommended by the US CDC. All infectious specimens will be transported in 
accordance with United States regulations (42 CFR 72) and in accordance with IATA. 
10.0 
ADMINISTRATIVE PROCEDURES 
10.1 
Protocol Registration 
Initial Registration of the protocol by the DAIDS PRO is required prior to implementation of this 
protocol. As part of this process, each site must have the protocol and protocol informed consent form(s) 
(ICFs) approved, as appropriate, by their IRB/EC and any other applicable regulatory entity (RE). Upon 
receiving final approval, sites will submit all required protocol registration documents to the DAIDS 
PRO at the DAIDS RSC. The DAIDS PRO will review the submitted protocol registration packet to 
ensure that all of the required documents have been received. In the case of Initial Registration, site-
specific ICFs WILL be reviewed and approved by the DAIDS PRO. Sites will receive an Initial 
Registration Notification from the DAIDS PRO that indicates successful completion of the protocol 
registration process. A copy of the Initial Registration Notification should be retained in the site's 
regulatory files. 
Following Initial Registration, any full protocol amendments require submission of a protocol 
registration packet to the DAIDS PRO as described above; however, the DAIDS PRO WILL NOT 
review and approve site-specific ICFs. Upon receiving final IRB/EC and any other applicable RE 
approval(s) for an amendment, sites should implement the amendment immediately. Sites will receive a 
Registration Notification when the DAIDS PRO receives a complete registration packet. A copy of the 
Amendment Registration Notification should be retained in the site’s regulatory files.   
There may be cases where a site submits as their Initial Registration a protocol amendment (Version 2.0 
or higher of a protocol); in such cases, the instructions for Initial Registration will be followed. 
For additional information on the protocol registration process and specific documents required for 
initial and amendment registrations, refer to the current version of the DAIDS Protocol Registration 
Manual, which can be found at https://rsc.niaid.nih.gov/clinical-research-sites/daids-protocol-
registration-policy-and-procedures-manual.  
10.2 
Study Activation 
Pending successful protocol registration and submission of all required documents, the HPTN LOC staff 
will “activate” a site. Study implementation may not be initiated until a study activation notice is 
provided to the site by the HPTN LOC. In addition, if study “activation” is determined to be necessary 
for any subsequent amendments, study implementation may not be initiated until a study activation 
notice is provided to the site by the HPTN LOC. 


 
HPTN 083-01, FINAL V3.0 
65 of 152 
2 July 2021 
10.3 
Study Coordination 
DAIDS holds the Investigational New Drug (IND) application for this study. Copies of all regulatory 
documents submitted to this IND by DAIDS will be forwarded to ViiV Healthcare for cross-referencing 
with the company’s other INDs for the study product(s). Assignment of all sponsor responsibilities for 
this study will be specified in a Clinical Trials Agreement executed between DAIDS and ViiV 
Healthcare. 
Study implementation will be directed by this protocol as well as the SSP Manual. The SSP Manual, 
which will include links to the DAIDS SOPs for Source Documentation and Essential Documents, as 
well as links to the Manual for Expedited Reporting of AEs to DAIDS and the DAIDS Toxicity Tables, 
will outline procedures for conducting study visits; data and forms processing; AE assessment, 
management and reporting; dispensing study products and documenting product accountability; and 
other study operations. 
Study CRFs will be developed by the study team and HPTN SDMC.  Data will be transferred to the 
HPTN SDMC, entered, and cleaned using the MediData Rave electronic data management system.  
Queries routinely will be generated and distributed to the study sites for verification and resolution. 
Close coordination between protocol team members will be necessary to track study progress, respond 
to queries about proper study implementation, and address other issues in a timely manner. Rates of 
accrual, adherence, follow-up, and AE incidence will be monitored closely by the team as well as the 
HPTN SMC. The protocol team’s CMC will address issues related to study eligibility and AE 
management and reporting as needed to assure consistent case management, documentation, and 
information-sharing across sites. 
10.4 
Study Monitoring 
On-site study monitoring will be performed in accordance with DAIDS policies. Study monitors will 
visit the site to: 
• verify compliance with human subjects and other research regulations and guidelines;  
• assess adherence to the study protocol, study-specific procedures manual, and local counseling 
practices; and 
• confirm the quality and accuracy of information collected at the study site and entered into the study 
database. 
Site investigators will allow study monitors to inspect study facilities and documentation (e.g., informed 
consent forms, clinic and laboratory records, other source documents, CRFs), as well as observe the 
performance of study procedures. Investigators also will allow inspection of all study-related 
documentation by authorized representatives of the HPTN LOC, HPTN SDMC, HPTN LC, NIAID 
and/or its contractors; NICHD and/or its contractors (including Westat); site IRBs/ECs; other local, US, 
or international regulatory authorities (including the OHRP and US FDA); or, if appropriate, the 
HPTN’s sIRB, Advarra, or ViiV. A site visit log will be maintained at each study site to document all 
visits. 


 
HPTN 083-01, FINAL V3.0 
66 of 152 
2 July 2021 
Monitoring visits may be conducted on-site or remotely. Remote visits may include remote source 
document verification using methods specified for this purpose by NIAID. Remote monitoring visits 
may be performed in place of, or in addition to onsite visits to ensure the safety of study participants and 
data integrity.41 The site will make available study documents for site monitors to review utilizing a 
secure platform that is HIPAA and 21 CFR Part 11 compliant. Potential platform options include: Veeva 
SiteVault, site-controlled SharePoint or cloud-based portal, direct access to Electronic Medical Record 
(EMR), and Medidata Rave Imaging Solution. Other secure platforms that are 21 CFR Part 11 compliant 
may be utilized, as allowed by the DAIDS Office of Clinical Site Oversight (OCSO). 
10.5 
Protocol Compliance 
The study will be conducted in full compliance with the protocol. The protocol will not be amended 
without prior written approval by the Protocol Chair and DAIDS Medical Officer. All protocol 
amendments must be submitted to and approved by the relevant IRB(s) and the DAIDS RSC prior to 
implementing the amendment. 
10.6 
Investigator's Records 
The IoR will maintain, and store in a secure manner, complete, accurate, and current study records 
throughout the study. In accordance with Federal regulations, for each of the investigational products 
tested, the IoR will retain all study records for at least two years following the date of marketing 
approval for the study product for the indication in which it was studied, or if other applicable laws, 
regulations, policies, or other requirements (e.g., State, country-specific, and local laws, and sponsor or 
institutional policies) exist, the most stringent retention period will be followed. European Medicines 
Authority (EMA) requirements, which will apply to the parent protocol (HPTN 083), were the most 
demanding identified by DAIDS at the study-wide level. Based upon EMA requirements, sites should 
therefore plan to retain files (and any other study documentation) for more than 15 years from the end of 
data collection, or longer if required by local regulations.  
If no marketing application is filed, or if the application is not approved, the records must be retained for 
two years after the US FDA is notified that the IND is discontinued, or if other applicable laws, 
regulations, policies, or other requirements (e.g., State, country-specific, and local laws, and sponsor or 
institutional policies) exist, the most stringent retention period will be followed.  
Study records include administrative documentation — including protocol registration documents and 
all reports and correspondence relating to the study, as well as documentation related to each participant 
screened and/or enrolled in the study. This includes informed consent forms, locator forms, CRFs, 
notations of all contacts with the participant, and all other source documents. 
Completion of a clinical research study occurs when the following activities have been completed: 
• All research-related interventions or interactions with human subjects (e.g. when all 
subjects are off study);  
• All protocol-required data collection of identifiable private information described in the 
IRB/EC-approved research plan;  
• All analysis of identifiable private information described in the IRB/EC-approved 
research plan;  


 
HPTN 083-01, FINAL V3.0 
67 of 152 
2 July 2021 
• Primary analysis of either identifiable private or de-identified information.  
10.7 
Use of Information and Publications 
Publication of the results of this study will be governed by HPTN policies.  Any presentation, abstract, 
or manuscript will be submitted by the Investigator to the HPTN Manuscript Review Committee 
(MRC), DAIDS, and ViiV Healthcare for review prior to submission. 


 
HPTN 083-01, FINAL V3.0 
68 of 152 
2 July 2021 
11.0 
REFERENCES 
 
1. 
World Health Organization. Department of Maternal Newborn Child and Adolescent Health. 
Health for the world’s adolescents: A second chance in the second decade. Summary. Geneva, 
Switzerland: WHO, Department of Maternal, Newborn, Child and Adolescent Health;2014. 
2. 
UNICEF. Towards an AIDS-free Generation -- Children and AIDS: Sixth stocktaking report, 
2013. New York, New York: UNICEF. 
3. 
UNAIDS. The Gap Report – July 2014 Geneva: Switzerland.2014. 
4. 
WHO. Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key 
populations. . Geneva, Switzerland.2014. 
5. 
CDC. HIV among Youth Fact Sheet. . Atlanta, Georgia, United States. March 2014 2014. 
6. 
McKinnon LR, Gakii G, Juno JA, et al. High HIV risk in a cohort of male sex workers from 
Nairobi, Kenya. Sexually Transmitted Infections. 2013:[8] p. 
7. 
Hosek SG, Rudy B, Landovitz R, et al. An HIV Preexposure Prophylaxis Demonstration Project 
and Safety Study for Young MSM. JAIDS Journal of Acquired Immune Deficiency Syndromes. 
2017;74(1):21-29. 
8. 
Hosek S, Landovitz R, Rudy B, et al. The adolescent trials network for HIV/AIDS interventions 
(ATN). An HIV pre-exposure prophylaxis (PrEP) demonstration project and safety study for 
adolescent MSM ages 15–17 in the United States (ATN 113). Paper presented at: International 
AIDS Conference.; July 19 2016., 2016; Durban, South Africa. 
9. 
Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in 
men who have sex with men. N Engl J Med. 2010;363(27):2587-2599. 
10. 
Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection in 
injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, 
double-blind, placebo-controlled phase 3 trial. The Lancet. 2013;381(9883):2083-2090. 
11. 
Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral Preexposure Prophylaxis for 
Heterosexual HIV Transmission in Botswana. New England Journal of Medicine. 
2012;367(5):423-434. 
12. 
Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in 
heterosexual men and women. N Engl J Med. 2012;367(5):399-410. 
13. 
McCormack S, Dunn DT, Desai M, et al. Pre-exposure prophylaxis to prevent the acquisition of 
HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label 
randomised trial. The Lancet. 2016;387(10013):53-60. 
14. 
Grant RM, Anderson PL, McMahan V, et al. Uptake of pre-exposure prophylaxis, sexual 
practices, and HIV incidence in men and transgender women who have sex with men: a cohort 
study. The Lancet Infectious Diseases. 2014;14(9):820-829. 
15. 
WHO. Guideline on when to start Antiretroviral Therapy and on Pre-Exposure Prophylaxis for 
HIV. 2015. 
16. 
U.S. Public Health Service. Preexposure prophylaxis for the prevention of HIV infection in the 
United States - 2017 update. A clinical practice guideline. . 2018. 
17. 
LaGreca AM, Schuman W. Adherence to prescribed medical regimens.  . In: Roberts MC, ed. 
Handbook of Pediatric Psychology. 2nd ed. New York, NY, USA.: Guilford Press.; 1995. 
18. 
Murphy DA, Wilson CM, Durako SJ, Muenz LR, Belzer M. Antiretroviral medication adherence 
among the REACH HIV-infected adolescent cohort in the USA. AIDS Care. 2001;13(1):27-40. 
19. 
Rome E. Use of long-acting reversible contraceptives to reduce the rate of teen pregnancy. 
Cleveland Clinic Journal of Medicine. 2015;82(suppl 1):S8-S12. 


 
HPTN 083-01, FINAL V3.0 
69 of 152 
2 July 2021 
20. 
Rosenberg MJ, Waugh MS, Meehan TE. Use and misuse of oral contraceptives: Risk indicators 
for poor pill taking and discontinuation. Contraception. 1995;51(5):283-288. 
21. 
Bureau PR. 2019 Family Planning Data Sheet. . Washington, DC, USA.2019. 
22. 
Reece M, Herbenick D, Schick V, Sanders SA, Dodge B, Fortenberry JD. Condom Use Rates in 
a National Probability Sample of Males and Females Ages 14 to 94 in the United States. The 
Journal of Sexual Medicine. 2010;7:266-276. 
23. 
Biello KB, Hosek S, Drucker MT, et al. Preferences for Injectable PrEP Among Young U.S. 
Cisgender Men and Transgender Women and Men Who Have Sex with Men. Archives of Sexual 
Behavior. 2017;47(7):2101-2107. 
24. 
Biello K, Hosek S, Coffey-Esquivel J, et al. Acceptability of and Preference for Injectable PrEP 
among Young U.S. Men, Transgender Women and Transgender Men who Have Sex with Men. . 
Paper presented at: HIV R4P Conference.2016; Chicago, IL, USA. 
25. 
Spreen WR, Margolis DA, Pottage JC. Long-acting injectable antiretrovirals for HIV treatment 
and prevention. Current Opinion in HIV and AIDS. 2013;8(6):565-571. 
26. 
Hume M, Lewis LL, Nelson RM. Meeting the goal of concurrent adolescent and adult licensure 
of HIV prevention and treatment strategies. J Med Ethics. 2017;43(12):857-860. 
27. 
Bekker LG, Slack C, Lee S, Shah S, Kapogiannis B. Ethical issues in adolescent HIV research in 
resource-limited countries. J Acquir Immune Defic Syndr. 2014;65 Suppl 1:S24-28. 
28. 
Shah SK, Allison SM, Kapogiannis BG, Black R, Dawson L, Erbelding E. Advancing 
independent adolescent consent for participation in HIV prevention research. J Med Ethics. 
2018;44(7):431-433. 
29. 
Glidden DV, Amico KR, Liu AY, et al. Symptoms, Side Effects and Adherence in the iPrEx 
Open-Label Extension. Clin Infect Dis. 2016;62(9):1172-1177. 
30. 
Spinner CD, Boesecke C, Zink A, et al. HIV pre-exposure prophylaxis (PrEP): a review of 
current knowledge of oral systemic HIV PrEP in humans. Infection. 2016;44(2):151-158. 
31. 
Mujugira A, Baeten J, Kidoguchi L, et al. High levels of viral suppression among East African 
HIV-infected women and men in serodiscordant partnerships initiating antiretroviral therapy 
with high CD4 counts and during pregnancy. AIDS Res Hum Retroviruses. 2018;34(2):140-147. 
32. 
Radzio J, Spreen W, Yueh YL, et al. The long-acting integrase inhibitor GSK744 protects 
macaques from repeated intravaginal SHIV challenge. Science Translational Medicine. 
2015;7(270):270ra275-270ra275. 
33. 
Andrews CD, Spreen WR, Mohri H, et al. Long-Acting Integrase Inhibitor Protects Macaques 
from Intrarectal Simian/Human Immunodeficiency Virus. Science. 2014;343(6175):1151-1154. 
34. 
Min S, DeJesus E, McCurdy L, et al. Pharmacokinetics (PK) and safety in healthy and HIV-
infected subjects and short-term antiviral efficacy of S/GSK 1265744, a next generation once 
daily HIV integrase inhibitor [Abstract no. H-1228]. Paper presented at: 9th Interscience 
Conference on Antimicrobial Agents and Chemotherapy 2009; San Francisco, CA. 
35. 
Spreen W, Min S, Ford SL, et al. Pharmacokinetics, safety, and monotherapy antiviral activity of 
GSK1265744, an HIV integrase strand transfer inhibitor. HIV clinical trials. 2013;14(5):192-
203. 
36. 
Margolis D, Brinson C, Eron J, et al. 744 and Rilpivirine as Two-Drug Oral Maintenance 
Therapy: LAI116482 (LATTE) Week 48 Results. Abstract 91LB. Paper presented at: 21st 
Conference on Retrovirus and Opportunistic Infections 2014; Boston, MA. 
37. 
Landovitz R DD, Clement M, et al. HPTN083 interim results: Pre-exposure prophylaxis (PrEP) 
containing long-acting injectable cabotegravir (CAB-LA) is safe and highly effective for 


 
HPTN 083-01, FINAL V3.0 
70 of 152 
2 July 2021 
cisgender men and transgender women who have sex with men (MSM,TGW)  AIDS 2020.; 
2020; Virtual. 
38. 
Landovitz RJ, Eron JJ, Grinsztein G, al. e. Tail-phase safety, tolerability and pharmacokinetics of 
long-acting injectable cabotegravir in HIV-uninfected individuals: HPTN 077 final results. . 
Paper presented at: HIV Research for Prevention (HIV R4P). October 21-25 2018., 2018; 
Madrid, Spain. 
39. 
Hill A, Waters L, Pozniak A. Are new antiretroviral treatments increasing the risks of clinical 
obesity? J Virus Erad. 2019;5(1):41-43. 
40. 
Landovitz RJ, Zangeneh SZ, Chau G, et al. Cabotegravir is Not Associated with Weight Gain in 
HIV-uninfected Individuals in HPTN 077. Clin Infect Dis. 2019. 
41. 
FDA Guidance on Conduct of Clinical Trials of Medical Products During the COVID-19 Public 
Health Emergency: Guidance for Industry, Investigators, and Institutional Review Boards, 
March 2020, Updated on January 27, 2021. 
 


 
HPTN 083-01, FINAL V3.0 
71 of 152 
2 July 2021 
12.0 
APPENDICES I – XVI  


 
HPTN 083-01, FINAL V3.0 
 
 
 
 
 
72 of 152 
2 July 2021 
12.1 
APPENDIX I. SCHEDULE OF EVALUATIONS – ORAL PHASE (STEP 1) 
 
WEEKS in Study 
(Shaded column = dispense oral product) 
 
Screening 
WEEK 0 
Enrollment 
WEEK 2 
WEEK 4 
ADMINISTRATIVE, BEHAVIORAL, REGULATORY 
Informed consent  
X 
 
 
 
Locator information 
X 
X 
X 
X 
Demographic information1 
X 
X 
 
 
HIV prevention counseling  
X 
X 
X 
X 
Offer condoms  
X 
X 
X 
X 
Patient Health Questionnaire-9 (PHQ-9) 
 
X 
 
 
Behavioral/Acceptability Assessment (CASI)  
 
X 
 
X 
CLINICAL EVALUATIONS & PROCEDURES 
Dispense study product (enough for 5 weeks) 
 
X 
 
 
Observe participant take oral study product2 
 
X 
X 
X 
Adherence counseling/pill count (pill count Weeks 2 and 4 only) 
 
X 
X 
X 
Medical history, con meds, targeted physical exam3 
X 
X 
X 
X 
Hep B vaccination (if needed)4 
 
 
X 
 
Blood collection 
X 
X 
X 
X 
Urine collection  
X 
X 
 
 
Rectal swab collection 
X 
 
 
 
LOCAL LABORATORY EVALUATIONS & PROCEDURES 
HIV testing5 
X 
X 
X 
X 
HBV and HCV testing6 
X 
X 
 
 
CBC with differential 
X 
X 
X 
X 
Chemistry testing7 
X 
X 
X 
X 
Liver function tests8 
X 
X 
 
X 
Fasting lipid profile9 
 
X 
 
 
Syphilis testing 
X 
 
 
 
GC/CT testing (urine, rectal, and oral pharyngeal swabs) 
X 
 
 
 
Urinalysis (protein and glucose; this test can be done at either the clinic or in the local 
laboratory) 
 
X 
 
 
Plasma storage10  
X 
X 
X 
X 
 
FOOTNOTES FOR APPENDIX I: 
1 Demographics may be collected and reported at either Screening or Enrollment. 
2 Staff are required to observe participants take one pill at Enrollment. If participants return with their pills at Weeks 2 & 4, staff will observe participant take one pill then as well, 
unless the participant has already taken oral study product that day. Participants must not be asked to take a second dose of oral study product for the sake of observation.  


 
HPTN 083-01, FINAL V3.0 
 
 
 
 
 
73 of 152 
2 July 2021 
3  Full physical exam is to be conducted during Enrollment.  A targeted physical exam will be done at all other visits. Participant pulse, blood pressure and weight must be recorded 
at every visit.  BMI must be calculated.  
4 The initial dose of the Hep B vaccination will ideally be given at Week 2, though there is flexibility around the timing of the vaccination.  Subsequent doses may be given at 
different visits than indicated in this SOE, as long as sites follow manufacturer guideline timing. 
5 The HIV testing algorithm is provided in the SSP Manual. Testing for acute HIV must be negative and must be performed within the 14 days prior to enrollment of the 
participant. If HIV rapid testing is indicated, this testing may be performed in the clinic or the laboratory.  At least one HIV assay result must be available and reviewed the same 
day as sample collection and before product is administered.  
6 Participants will be tested for Hepatitis B surface antibody (HBsAb), and Hepatitis B core antibody (HBcAb, total) at Screening or Enrollment. HbsAg and HCV Ab must be 
resulted and reviewed prior to enrollment.      
7 At Screening: Creatinine. At and after enrollment: BUN/urea, creatinine, CPK, calcium, phosphorous, glucose, amylase, and lipase. 
8 At Screening: ALT and TBili. At and after Enrollment: AST, ALT, total bilirubin, and alkaline phosphatase.  
9 Total cholesterol, HDL, triglycerides, and LDL (either calculated or measured). Participants must have fasted for at least 8 hours, preferably 12 hours, prior to sample collection. 
Do not collect or test if <8 hours fasting. 
10 Stored plasma will be used for Quality Assurance testing and other assessments at the HPTN LC (see Section 9). Assessments will be performed retrospectively; results will not 
be returned to study sites or participants, except as noted in SSP. Samples cannot be used by site or other lab for local purposes without specific instructions from the LC w/ CMC 
consult. 
 
 
 
  
 


 
HPTN 083-01, FINAL V3.0 
74 of 152 
2 July 2021 
12.2 
APPENDIX II. SCHEDULE OF EVALUATIONS – INJECTION PHASE (STEP 2) 
 
WEEKS in Study  
(shaded column = injection 
visit) 
Wk 
5 
Wk 
6 
Wk 
9 
Wk 
10 
Wk 
17 
Wk 
18 
Wk 
25 
Wk 
26 
Wk 
33 
Wk 
34 
ADMINISTRATIVE, BEHAVIORAL, REGULATORY 
Locator information 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HIV prevention counseling 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Condoms per local SOC 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Behavioral/Acceptability 
assessment (CASI) 
X 
 
X 
 
X 
 
X 
 
X 
 
Qualitative interviews begin 
(approximately) 
 
 
 
 
 
 
 
 
 
X 
CLINICAL EVALUATIONS & PROCEDURES 
Adherence, risk reduction 
counseling 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medical history1, concomitant 
medications, targeted physical 
exam 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hep B vaccination (if needed) 2 
 
X 
 
 
 
 
 
 
X 
 
Blood collection 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine collection  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Rectal swab collection 
 
 
 
 
X 
 
 
 
X 
 
Injections for all participants 
X 
 
X 
 
X 
 
X 
 
X 
 
ISR evaluation  
 
X 
 
X 
 
X 
 
X 
 
X 
Step 3 product choice 
discussion 
 
 
 
 
 
 
 
 
X 
X 
Interviewer administered 
product choice assessment 
 
 
 
 
 
 
 
 
 
X 
If product chosen is oral 
PrEP: Provision of 
Tenofovir/Emtricitabine 
(Trade name: TDF/FTC, 
Truvada®) (3 months’ worth) 
 
 
 
 
 
 
 
 
 
X 
LOCAL LABORATORY EVALUATIONS & PROCEDURES 
HIV testing3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CBC with differential 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chemistry testing4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Liver function testing5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Fasting lipid profile6 
 
 
 
 
 
 
 
 
 
X 
Syphilis testing 
 
 
 
 
 
 
 
 
X 
 
GC/CT testing (urine, rectal, 
and oral pharyngeal swabs) 
 
 
 
 
X 
 
 
 
X 
 
Urinalysis (protein, glucose; at 
the clinic or local lab) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Plasma storage7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 


 
HPTN 083-01, FINAL V3.0 
75 of 152 
2 July 2021 
FOOTNOTES FOR APPENDIX II: 
1 Medical history must include pulse, blood pressure, weight and Body Mass Index (BMI) calculated at each visit 
2  The initial dose of the HBV vaccination is ideally given at Week 2, though there is flexibility around the timing of the 
vaccination.  Subsequent doses may be given at different visits than indicated in this SOE, as long as sites follow 
manufacturer guideline timing. 
3 The HIV testing algorithm is provided in the SSP Manual. If HIV rapid testing is indicated, this testing may be performed in 
the clinic or the laboratory. At least one HIV assay result must be available and reviewed the same day as sample collection 
and before product is administered.  
4 BUN/urea, creatinine, CPK, calcium, phosphorous, glucose, amylase, and lipase. 
5 AST, ALT, TBili, and alkaline phosphatase.  
6 Total cholesterol, HDL, triglycerides, and LDL (either calculated or measured). Participants must have fasted for at least 8 
hours, preferably 12 hours, prior to sample collection. Do not collect or test if <8 hours fasting. For participants who switch 
to Step 3 early (without having completed all 5 injections), the fasting lipid profile will be taken at the first visit after they 
transition off injections.  
7  Stored plasma will be used for Quality Assurance testing and other assessments at the HPTN LC (see Section 9), including 
potential assay for plasma CAB concentrations.. Assessments will be performed retrospectively; results will not be returned 
to study sites or participants, except as noted in the SSP Manual. Samples cannot be used by site or other lab for local 
purposes without specific instructions from the LC w/ CMC consult. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
HPTN 083-01, FINAL V3.0 
76 of 152 
2 July 2021 
12.3 
APPENDIX III. SCHEDULE OF EVALUATIONS –FOLLOW-UP PHASE (STEP 3-
ORAL PrEP)     
 
WEEKS SINCE LAST INJECTION  
Wk 
+8 
Wk 
+12 
Wk 
+24 
Wk 
+36 
Wk 
+48 
Early 
Discontinuation 
ADMINISTRATIVE, BEHAVIORAL, REGULATORY 
 
Locator information 
X 
X 
X 
X 
X 
X 
HIV prevention & risk reduction counseling 
X 
X 
X 
X 
X 
X 
Condoms per local SOC 
X 
X 
X 
X 
X 
X 
Behavioral/Acceptability assessment (CASI) 
 
X 
X 
X 
X 
X 
CLINICAL EVALUATIONS & PROCEDURES 
 
Qualitative interviews continue 
(approximately) 
 
X 
X 
 
 
 
Medical history1, concomitant medications, 
targeted physical exam 
 
X 
X 
X 
X 
 
Hep B vaccination (if needed) 2 
 
 
 
 
 
X 
Blood collection 
X 
X 
X 
X 
X 
 
Urine collection 
 
 
X 
 
X 
X 
Rectal swab collection 
 
 
X 
 
X 
 
Provision of Tenofovir/Emtricitabine (Trade 
name: TDF/FTC, Truvada®) (3 months’ 
worth) 
 
X 
X 
X 
 
X 
LOCAL LABORATORY EVALUATIONS & PROCEDURES 
 
HIV testing3 
 
X 
X 
X 
X 
 
CBC with differential 
 
 
X 
 
X 
X 
Chemistry testing4 
 
X 
X 
X 
X 
X 
Liver function testing5 
 
X 
X 
X 
X 
X 
Syphilis testing 
 
 
X 
 
 
X 
GC/CT testing (urine, rectal, and oral 
pharyngeal swabs) 
 
 
X 
 
X 
 
Urinalysis (protein, glucose; at the clinic or 
local lab) 
 
 
X 
 
X 
X 
Plasma storage6 
X 
X 
X 
X 
X 
 
DBS storage 
 
X 
X 
 
X 
 
HBsAb and HBcAb7 
 
 
 
 
X 
X 
HCVAb 
 
 
 
 
X 
X 
 
FOOTNOTES FOR APPENDIX III: 
1 Medical history must include pulse, blood pressure, weight and Body Mass Index (BMI) calculated at each visit  
2  The initial dose of the HBV vaccination is ideally given at Week 2, though there is flexibility around the timing of the 
vaccination. Subsequent doses may be given at different visits than indicated in this SOE, as long as sites follow 
manufacturer guideline timing. 
3 The HIV testing algorithm is provided in the SSP Manual. If HIV rapid testing is indicated, this testing may be performed in 
the clinic or the laboratory. At least one HIV assay result must be available and reviewed the same day as sample collection 
and before product is administered. 
4 Creatinine only (for Step 3-Oral PrEP).. 
5 AST, ALT, TBili, and alkaline phosphatase. 


 
HPTN 083-01, FINAL V3.0 
77 of 152 
2 July 2021 
6 Stored plasma will be used for Quality Assurance testing and other assessments at the HPTN LC (see Section 9) including 
potential assay for plasma CAB concentrations. Assessments will be performed retrospectively; results will not be returned to 
study sites or participants, except as noted in SSP. Samples cannot be used by site or other lab for local purposes without 
specific instructions from the LC w/ CMC consult. 
7 HBsAb and HBcAb will be tested in participants who received the HBV vaccine. 


 
HPTN 083-01, FINAL V3.0 
78 of 152 
2 July 2021 
12.4 
APPENDIX IV. SCHEDULE OF EVALUATIONS – FOLLOW-UP PHASE (STEP  
3-INJECTION) 
 
WEEKS SINCE LAST INJECTION  
Wk 
+8 
Wk 
+16 
Wk 
+24 
Wk 
+32 
Wk 
+40 
Wk 
+48 
Early 
Discontinuation 
ADMINISTRATIVE, BEHAVIORAL, REGULATORY 
Locator information 
X 
X 
X 
X 
X 
X 
X 
HIV prevention & risk reduction counseling 
X 
X 
X 
X 
X 
X 
X 
Condoms per local SOC 
X 
X 
X 
X 
X 
X 
X 
Behavioral/Acceptability assessment (CASI) 
 
X 
X 
X 
X 
X 
X 
CLINICAL EVALUATIONS & PROCEDURES 
Qualitative interviews continue 
(approximately) 
 
X 
X 
 
 
 
 
Medical history1, concomitant medications, 
targeted physical exam 
 
X 
X 
X 
X 
X 
 
Hep B vaccination (if needed) 2 
 
 
 
 
 
 
X 
Blood collection 
X 
X 
X 
X 
X 
X 
 
Urine collection  
 
 
X 
 
 
X 
X 
Rectal swab collection 
 
 
X 
 
 
X 
 
Injections (CAB LA) 
X 
X 
X 
X 
X 
X 
X 
ISR evaluation 
X 
X 
X 
X 
X 
X 
X 
Adherence counselling 
X 
X 
X 
X 
X 
X 
X 
LOCAL LABORATORY EVALUATIONS & PROCEDURES 
HIV testing3 
X 
X 
X 
X 
X 
X 
X 
CBC with differential 
 
 
X 
 
 
X 
 
Chemistry testing4 
X 
 
X 
 
 
X 
X 
Liver function testing5 
X 
 
X 
 
 
X 
X 
Syphilis testing 
 
 
X 
 
 
 
X 
GC/CT testing (urine, rectal, and oral 
pharyngeal swabs) 
 
 
X 
 
 
X 
X 
Plasma storage6 
X 
X 
X 
X 
X 
X 
 
DBS storage 
 
X 
X 
 
X 
X 
 
HBsAb and HBcAb7 
 
 
 
 
 
X 
X 
HCVAb 
 
 
 
 
 
X 
X 
 
FOOTNOTES FOR APPENDIX IV: 
1 Medical history must include pulse, blood pressure, weight and Body Mass Index (BMI) calculated at each visit. 
2  The initial dose of the HBV vaccination is ideally given at Week 2, though there is flexibility around the timing of the 
vaccination. Subsequent doses may be given at different visits than indicated in this SOE, as long as sites follow 
manufacturer guideline timing. 
3 The HIV testing algorithm is provided in the SSP Manual. If HIV rapid testing is indicated, this testing may be performed in 
the clinic or the laboratory. At least one HIV assay result must be available and reviewed the same day as sample collection 
and before product is administered. 
4 BUN/urea, creatinine, CPK, calcium, phosphorous, glucose, amylase, and lipase. 
5 AST, ALT, TBili, and alkaline phosphatase. 
6 Stored plasma will be used for Quality Assurance testing and other assessments at the HPTN LC (see Section 9) including 
potential assay for plasma CAB concentrations. Assessments will be performed retrospectively; results will not be returned to 


 
HPTN 083-01, FINAL V3.0 
79 of 152 
2 July 2021 
study sites or participants, except as noted in SSP. Samples cannot be used by site or other lab for local purposes without 
specific instructions from the LC w/ CMC consult. Blood collected for plasma storage must be collected prior to injection. 
7 HBsAb and HBcAb will be tested in participants who received the HBV vaccine. 
 
 


 
HPTN 083-01, FINAL V3.0 
80 of 152 
2 July 2021 
12.5 
APPENDIX V: SCHEDULE OF ADDITIONAL PROCEDURES FOR 
REACTIVE/POSITIVE HIV TESTS 
(For enrolled participants) 
 
Note 1: The procedures listed for the HIV Confirmation Visit apply to participants who acquire HIV 
infection at any time during the study. The procedures listed for Weeks 12, 24, 36, and 48 apply to 
participants who acquire HIV infection after having one or more injections. Participants who acquire 
HIV in Step 3 may undergo similar procedures as listed in Weeks 12, 24, 36, and 48, and will be 
determined by the members of the protocol team. Note that participants who acquire HIV-infection 
during Step 1 will permanently discontinue study product, will be terminated from the study, and be 
referred for HIV-related care.   
 
FOOTNOTES FOR APPENDIX V: 
1 The HIV confirmatory visit must be held on a different day from the visit where the participant had their initial 
reactive/positive HIV test.  The testing algorithm for the HIV Confirmation Visit is provided in the SSP Manual. If HIV rapid 
testing is included in the HIV testing algorithm, this testing may be performed in the clinic or the laboratory.     
Participants who acquire HIV infection in Injection and Follow-up Phase only 
 
HIV 
Confirmation 
Visit 
Week 12 
Week 24 
Week 36 
Week 48 
ADMININISTRATIVE, BEHAVIORAL, REGULATORY 
Locator information 
X 
X 
X 
X 
X 
Offer condoms 
X 
X 
X 
X 
X 
HIV counseling 
X 
 
 
 
 
CLINICAL EVALUATIONS AND PROCEDURES 
History, con meds, targeted 
physical exam 
X 
X 
X 
X 
X 
Blood collection 
X 
X 
X 
X 
X 
LOCAL LABORATORY EVALUATIONS 
HIV testing1 
X 
 
 
 
 
CD4 cell count 
X 
 
X 
 
X 
HIV viral load testing 
X 
 
X 
 
X 
HIV resistance testing2 
X 
 
 
 
 
Chemistry testing3 
 
X 
X 
X 
X 
Liver function testing4 
 
X 
X 
X 
X 
Plasma storage5 
X 
X 
X 
X 
X 
DBS storage 
X 
 
 
 
 


 
HPTN 083-01, FINAL V3.0 
81 of 152 
2 July 2021 
2 Sites may collect specimens for resistance testing at a local laboratory to assist with clinical management; results from 
resistance testing performed at local laboratories will not be reported to the SDMC.  Stored plasma may not be used real-
time/local resistance testing; additional samples must be collected for this testing.   
3 Required chemistry testing: BUN/urea, creatinine, CPK, calcium, phosphorous, glucose, amylase, and lipase.  
4 Required LFTs: AST, ALT, total bilirubin, and alkaline phosphatase.  
5 Stored plasma will be used for Quality Assurance testing and other assessments at the HPTN LC (see Section 9), including 
potential assay for plasma CAB concentrations. Assessments will be performed retrospectively; results will not be returned to 
study sites or participants, except as noted in Section 9.0. Samples cannot be used by site or other lab for local purposes 
without specific instructions from the LC w/ CMC consult. 
 


 
HPTN 083-01, FINAL V3.0 
82 of 152 
2 July 2021 
12.6 
APPENDIX VI: TOXICITY MANAGEMENT 
Toxicity Management General Guidance 
In general, the IoR has the discretion to hold study product at any time if she/he feels that continued 
product use would be harmful to the participant or interfere with treatment deemed clinically necessary 
according to the judgment of the IoR. In addition, a CMC has been established for this study. The 
CMC’s responsibilities will include consultation and decision-making regarding management of 
toxicities and study product administration, including product resumption following the occurrence of 
certain types of toxicities and/or permanent discontinuation. Throughout this appendix are examples of 
AEs that require consultation with the CMC; in all such cases, the CMC should be notified as soon as 
possible and ideally within 72 hours of site awareness of the AE in question. IoRs also should consult 
the CMC for further guidance in restarting study product or progressing to permanent discontinuation.  
The following general guidance refers to all AEs except for ALT. Refer to the table below for specific 
guidance for ALT. 
Grade 1 or 2 
In general, participants who develop a Grade 1 or 2 AE regardless of relatedness to study product, and 
that is not specifically addressed elsewhere in the protocol or in the Tables below may continue use of 
the study product per protocol.             
Grade 3 
For participants who develop a Grade 3 AE or toxicity that is not specifically addressed elsewhere in the 
protocol or in the Tables below and is judged to be related to study product by the IoR, study product 
use should be temporarily discontinued in consultation with the CMC. In general, and unless otherwise 
decided in consultation with the CMC, the IoR should re-evaluate the participant until resolution of the 
toxicity.  
Related: 
For Grade 3 AEs deemed related to study product, the study product should be 
permanently discontinued if improvement to severity ≤ Grade 2 cannot be 
documented within 4 weeks of receipt of the initial result. If study product is resumed 
and the same Grade 3 AE recurs at any time, the IoR must consult the CMC for 
further guidance on holding of study product, frequency of reevaluation or 
progression to permanent discontinuation of the study product.   
 
Unrelated: 
For Grade 3 AEs deemed unrelated to study product, the CMC should be consulted 
for further management recommendations.  
Grade 4 
Participants who develop a Grade 4 AE or toxicity that is not specifically addressed elsewhere in the 
protocol or in the Tables below (regardless of relationship to study product) must have the study product 
temporarily discontinued. The IoR must consult the CMC and continue the temporary study product 
hold until a recommendation is obtained from the CMC.  
 
In general, study product use will not be resumed if the Grade 4 AE is considered related to study 


 
HPTN 083-01, FINAL V3.0 
83 of 152 
2 July 2021 
product use. If, in consultation with the CMC, study product use is resumed and the same Grade 4 AE 
recurs at Grade 4 level at any time, study product must then be permanently discontinued. 
General Criteria for Discontinuation of Study Product 
Participants may voluntarily discontinue the study product for any reason at any time.   IoRs will 
permanently discontinue participants from study product per protocol for any of the specific criteria 
below, which may be further clarified in the SSP Manual. IoRs also may permanently discontinue 
participants for reasons not shown here or in the SSP Manual (e.g., to protect participants’ safety and/or 
if participants are unable or unwilling to comply with study product use procedures). In such cases, the 
IoR or designee must first query the CMC for review. The CMC will provide a written response to the 
site indicating whether the CMC has recommended permanent discontinuation of study product based 
on careful review of all relevant data. It should be noted that the safety of the participant should always 
take precedence, and therefore, an IoR may determine that study product be permanently discontinued 
before the CMC has time to respond. This is acceptable, and in such cases, the CMC should be notified 
as soon as possible regarding the nature of the case and the course of action taken.   
The criteria for permanent discontinuation of study product use for an individual participant are: 
• Study product-related toxicity requiring permanent discontinuation of study product per the 
guidelines above and below 
• Completion of regimen as defined in the protocol 
• Request by participant to terminate study product 
• Clinical reasons determined by the IoR  
• Acquires HIV infection or HBV infection   
Study product will be temporarily withheld from a participant for any of the following reasons: 
• Report of use of prohibited concomitant medications as described in Protocol Section 4.4.  Study 
product use may resume upon consultation with the CMC and when the participant reports that he is 
no longer taking the prohibited medication, provided other reasons for temporary study product 
hold/permanent discontinuation do not apply. The CMC should be consulted in all cases where a 
participant reports taking a prohibited product during the course of the study.   
• The participant is unable or unwilling to comply with required study procedures such as HIV testing 
and routine laboratory assessments, or otherwise might be put at undue risk to their safety and well-
being by continuing study product use, according to the judgment of the IoR. The IoR must consult 
the CMC on all temporary study product holds instituted for this reason for further guidance on 
resuming study product use, continuing the temporary hold, or progressing to permanent 
discontinuation.   
• The participant has one or more reactive HIV test results or expresses a concern about having acute 
HIV infection. Criteria for resuming use of study product in these circumstances are defined in the 
protocol and SSP Manual. 


 
HPTN 083-01, FINAL V3.0 
84 of 152 
2 July 2021 
Oral Phase: 
Participants who temporarily or permanently discontinue study product during the Step 1, Oral Run-in 
Phase, will be instructed to return all study products as soon as possible.   
Injection Phase: 
Participants who have received at least one injection and refuse further injections or discontinue due to 
an AE will be transitioned to quarterly follow-up. 
 
 
 


 
HPTN 083-01, FINAL V3.0 
85 of 152 
2 July 2021 
GUIDANCE ON TOXICITY MANAGEMENT FOR SPECIFIED TOXICITIES: 
Nausea, Vomiting, and Diarrhea 
CONDITION AND 
SEVERITY 
IMMEDIATE 
ACTION 
FOLLOW-UP AND MANAGEMENT 
Nausea, Vomiting, and Diarrhea 
Grade 1 and 2 
Continue study 
product  
Treat symptomatically with hydration, oral 
antiemetic therapies or antiemetic suppositories 
at the discretion of the IoR. The IoR should 
order any clinically relevant laboratory 
analyses (per judgment of the IoR). 
Grade ≥ 3  
Discontinue study 
product 
temporarily 
Participants with Grade  3 nausea, vomiting, 
or diarrhea, for which an alternative etiology is 
not established, must discontinue the study 
product temporarily until Grade 2 or lower and 
be treated symptomatically. Should 
condition(s) not improve to Grade ≤ 2 within 7 
days, the IoR should consult the CMC for 
guidance on continuing the temporary 
discontinuation or progressing to permanent 
discontinuation of study product. 
 


 
HPTN 083-01, FINAL V3.0 
86 of 152 
2 July 2021 
GUIDANCE ON TOXICITY MANAGEMENT FOR SPECIFIED TOXICITIES: 
ALT 
Note for all Grades:  
All study participants will be negative for HBsAg at study entry, and participants who enter the study 
without evidence of immunity to HBV will be provided HBV vaccination. Therefore, pre-existing HBV 
infection is not likely to be a cause of AST/ALT elevations. 
Careful assessments should be done to rule out the use of alcohol, lactic acidosis syndrome, non-study 
medication-related product toxicity, herbal medications/supplements, or viral hepatitis as the cause of 
elevation in AST or ALT of any Grade. The participant must be carefully assessed for any symptoms or 
signs of hepatotoxicity, including fatigue, malaise, anorexia and nausea, jaundice, acholic stools, right 
upper quadrant pain, or hepatomegaly. If the AST/ALT elevation is considered most likely to be due to 
concomitant illness or medication, standard management, including discontinuation of the likely 
causative agent, if possible, should be undertaken. If symptoms or signs of clinical hepatitis are present, 
study product must be held or discontinued. In addition, all participants with elevated values should be 
considered for testing for hepatitis A, B, and C infection.   
Note the following for cases of exercise-induced CPK abnormalities:   
Note the following for cases of exercise-induced CPK abnormalities: Cases of CPK abnormality > 
Grade 3 or higher, presumed to be exercise induced, accompanied by < Grade 3 ALT must be brought to 
the attention of the CMC for adjudication of further management and further administration of study 
product. Grades 3 and 4 elevations in ALT, regardless of CK elevation will prompt permanent 
discontinuation of study product and the participant will be followed annually for HIV testing only until 
the conclusion of Step 2 of the study. All such cases must be reported to the CMC.   
 
 
 
 
 
 
 
 
 
 
 


 
HPTN 083-01, FINAL V3.0 
87 of 152 
2 July 2021 
GUIDANCE ON TOXICITY MANAGEMENT FOR SPECIFIED TOXICITIES: 
CONDITION AND 
SEVERITY 
FOLLOW-UP AND MANAGEMENT 
ELEVATIONS in ALT  
Grade 2 and higher – 
Oral Phase 
Oral phase: A Grade 2 ALT abnormality reported at Week 2 or Week 4, 
regardless of relatedness to the study product, should be confirmed within 
one week. Oral study drug may continue until the confirmatory results are 
available; no injections should be administered until confirmatory results 
are available during consideration of the Week 4 ALT value. If the repeat 
value is < Grade 2 at Week 3, study drug may continue to Week 4. If the 
repeat value is < Grade 2 at Week 4, the participant may proceed to the 
injection phase. If the repeat value is Grade 2 or higher at Week 4, study 
product should be stopped, and the participant will be discontinued from the 
study. All such cases must be reported to the CMC. In addition, participants 
will be followed with weekly ALT assessments until they return to < Grade 
1.   
 
Grade 3 and higher – 
Oral Phase 
Oral Phase: A Grade 3 or higher ALT abnormality, regardless of 
relatedness to the study product, will result in permanent study product 
discontinuation and will prohibit a participant from entering the injection 
phase of the study. All such cases must be reported to the CMC. In addition, 
participants will be followed with weekly ALT assessments until they 
return to < Grade 1.   


 
HPTN 083-01, FINAL V3.0 
88 of 152 
2 July 2021 
CONDITION AND 
SEVERITY 
FOLLOW-UP AND MANAGEMENT 
ELEVATIONS in ALT  
Grade 2 and higher – 
Injection Phase 
Injection phase: The CMC should be notified as soon as possible.  
 
For a Grade 2 ALT, the CMC will determine whether further injections may 
be given in cases where levels are ≤ Grade 2 prior to the next scheduled 
injection. Unless otherwise specified by the CMC, for Grade 2 ALT, 
repeat testing should be performed weekly until levels are ≤ Grade 1.   
 
Grade 3 and higher – 
Injection Phase 
Injection Phase: For Grade 3 and higher ALT, study product will be 
permanently discontinued. For Grade 3 and 4 ALT, repeat testing should be 
performed as soon as possible, and participants should be followed weekly 
until levels are ≤ Grade 1. Participants who are permanently discontinued 
from study product should continue to be followed 48 weeks post-last 
injection. 


 
HPTN 083-01, FINAL V3.0 
89 of 152 
2 July 2021 
GUIDANCE ON TOXICITY MANAGEMENT FOR SPECIFIED TOXICITIES: 
Creatinine Clearance 
CONDITION AND 
SEVERITY 
IMMEDIATE 
ACTION 
FOLLOW-UP AND MANAGEMENT 
CREATININE CLEARANCE 
Estimated CrCl< 60 
mL/min 
Discontinue study 
product temporarily 
If the calculated creatinine clearance is 
<60mL/min, it should be confirmed within 1 
week of the receipt of the results, and the 
CMC should be consulted. 
Confirmed CrCl< 60 
mL/min  
Permanently 
discontinue study 
product  
If the calculated creatinine clearance is 
confirmed to be <60 mL/min, the CMC must 
be notified and the study product must be 
discontinued.  Participants who fail to have a 
confirmed test within 2 weeks of receiving the 
initial result, should be discontinued from use 
of the study product until CMC adjudication 
and recommendation for further testing and 
follow-up. 
Re-testing result is             
≥60 mL/min 
Consult CMC for 
guidance 
If re-testing yields a result ≥ 60 mL/min, the 
IoR must consult the CMC for further 
guidance on resuming study product use, 
continuing the hold temporarily, or 
progressing to permanent discontinuation. 
If the IoR, in consultation with the CMC, has 
determined that the case has stabilized, it may 
be possible to decrease the frequency of 
follow-up laboratory testing in addition to 
resumption of study product.  
 


 
HPTN 083-01, FINAL V3.0 
90 of 152 
2 July 2021 
GUIDANCE ON TOXICITY MANAGEMENT FOR SPECIFIED TOXICITIES: 
Creatine Phosphokinase (CPK) 
Note the following for cases of exercise-induced CPK abnormalities:   
Note the following for cases of exercise-induced CPK abnormalities: Cases of CPK abnormality > 
Grade 3 or higher, presumed to be exercise induced, accompanied by < Grade 3 ALT must be brought to 
the attention of the CMC for adjudication of further management and further administration of study 
product. Grades 3 and 4 elevations in ALT, regardless of CK elevation will prompt permanent 
discontinuation of study product and the participant will be followed for 48 weeks post-last injection. 
All such cases must be reported to the CMC.   
 
CONDITION AND 
SEVERITY 
IMMEDIATE ACTION 
FOLLOW-UP AND MANAGEMENT 
Creatine Phosphokinase 
Grade 3  
Continue study product 
until repeat test results are 
available 
A Grade 3 or higher elevation in CPK 
should result in a repeat assessment 
within 2-4 weeks to ensure the result is 
transient or due to exercise and will not 
require a change in study treatment. A 
history regarding use of products known 
to cause increase of CPK (such as 
statins), physical activity, or exercise 
preceding the CPK evaluation should be 
obtained.  
Grade 4 
Continue study product 
until repeat test results are 
available if the elevation is 
thought to be possibly or 
probably related to study 
product. 
Grade 4 elevations in CPK should have a 
repeat assessment after the subject has 
abstained from exercise for >24 hours. 
For persistent Grade 4 CPK elevations 
that are considered possibly or probably 
related to the study product, study 
product should be discontinued and the 
participant should be followed on 
study/off study product.   


 
HPTN 083-01, FINAL V3.0 
91 of 152 
2 July 2021 
GUIDANCE ON TOXICITY MANAGEMENT FOR SPECIFIED TOXICITIES: 
Guidance for Injection Site Reactions (ISRs) 
The CMC must be informed of all Grade 3 or 4 ISRs to determine etiology and assess appropriate 
continued study participation. ISR discomfort can be managed symptomatically (e.g. cold/warm 
compress, acetaminophen, ibuprofen) if the reaction is interfering with the participant’s ability to 
perform activities of daily living.  
Guidance for Allergic Reactions 
Participants may continue to receive oral or injectable study product for Grade 1 or 2 allergic reactions 
at the discretion of the IoR or designee. The participant should be advised to contact the study site staff 
immediately if there is any worsening of symptoms or if further systemic signs or symptoms develop. 
Antihistamines, topical corticosteroids, or antipruritic agents may be prescribed.  
Participants with Grade ≥3 allergic reactions that are considered to be related to study product should 
permanently discontinue study product and continue to be followed quarterly. Participants should be 
treated as clinically appropriate and followed until resolution of the AE. 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
92 of 152 
2 July 2021 
12.7 
APPENDIX VII: INFORMED CONSENT FOR PARENTS/LEGAL GUARDIANS 
AND ASSENT FOR ADOLESCENT PARTICIPANTS AGES 14 – AGE OF MAJORITY 
 
Sponsor / Study Title: 
  
Division of AIDS (DAIDS), United States (US) National 
Institute of Allergy and Infectious Diseases (NIAID), Eunice 
Kennedy Shriver National Institute of Child Health and 
Human Development (NICHD), US National Institutes of 
Health (NIH) / “HPTN 083-01: Safety, Tolerability and 
Acceptability of Long-Acting Cabotegravir (CAB LA) for 
the Prevention of HIV among Adolescent Males – A sub-
study of HPTN 083” 
 
Protocol Number: 
 
HPTN 083-01 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
 
If you are a parent or legal guardian of a child participating on this study, throughout this document 
“you(r)” = “your child.” 
 
Key Information: 
 
The first two pages of this document include summary information about this study that will help 
you decide whether or not you should participate. More detailed information is provided after this 
summary section. 
 
 
About this research  
You are being asked to join a research study. Scientists do research to answer important questions which 
might help change or improve the way we do things in the future. This form explains the research study 
and your part in the study. Please read it carefully and take as much time as you need. Ask your study 
doctor or the study team to explain any words or information that you do not understand. You may take 
this description home and discuss it with your family or friends to help you decide.  
 
Taking part in this research study is voluntary 
You may choose not to take part in the study or may choose to leave the study at any time. Deciding not 
to participate, or deciding to leave the study later, will not result in any penalty or loss of benefits to 
which you are entitled and will not affect your relationship with the study site. 
 
Important Information  


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
93 of 152 
2 July 2021 
This information gives you an overview of the research. More information about these topics may be 
found in the pages that follow.  
 
1. Why is this research being done? 
There is a new drug called cabotegravir (CAB) that can treat people who have human 
immunodeficiency virus (HIV) infection. CAB is also being tested to see if it can protect people 
from getting HIV and has been found to be effective at preventing HIV among adult men and 
transgender women. In this study, we want to know if it is safe and acceptable for adolescents who 
do not have HIV to take CAB. For more information, please see the What is this Study About section 
below.  
 
2. What will happen to me during the study? 
You will move through the study in 3 steps: 
• Step 1: You will take one CAB pill every day for five weeks 
• Step 2: You will receive a total of 5 CAB injections over 6 months 
• Step 3: You will come to the clinic for study visits for up to one year. 
 
Different procedures are done at different study visits. The procedures include: 
• Physical examinations – We will examine you to check on your health by measuring height, 
weight, temperature and blood pressure.  
• Questions – We will ask general questions about your age, living situation, medical health, 
and as well as beliefs about HIV, opinions about taking pills and getting injections, sexual 
behavior, and any alcohol or drug use. 
• Counselling – We will discuss ways to protect you from getting HIV and offer condoms. We 
will discuss any challenges you have taking the CAB pill or attending study visits. 
• CAB pills or injection – During Step 1, we will explain how to take the study pills, watch you 
take a study pill, and explain any side effects the pills may cause. In Step 2 and Step 3 (if 
chosen), the CAB injection will be given into your buttock.  
• Laboratory tests – We will collect blood, urine, rectal swabs, and oral pharyngeal swabs to 
test for HIV, Hepatitis, liver and kidney health, cholesterol, and sexually transmitted 
infections (STIs). If you have an STI, you will be told so, and referred for appropriate 
treatment. 
• HIV Prevention – We will offer you Tenofovir/Emtricitabine (Trade name: TDF/FTC, 
Truvada®) tablets as pre-exposure prophylaxis (PrEP) after you stop the CAB injections. 
You may, instead, choose to stay on CAB LA injections. 
 
For more information on each procedure and when it happens, please see the What Will I have to Do 
in the Study section below.  
 
3. How long will I participate in the study? 
If you decide to join the study, participation will last about 1.5 years and include a maximum of 18 
study visits at this clinic. 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
94 of 152 
2 July 2021 
4. Will I benefit from the study? 
It is possible that you may benefit from taking part in this study.. The study drug being used has 
been shown to prevent HIV infections among some adults. You will get information about your 
health and the results of the tests, as well as treatment for sexually transmitted infections. The 
counseling you get during this study may help you avoid HIV and other sexually transmitted 
infections. For more information, please see the What are the Potential Benefits of Taking Part in the 
Study section below.  
 
5. Will taking part in the study expose me to risks? 
Taking part in this research may expose you to risks. We may not know or understand all the risks at 
this time. Some people may experience side effects or discomfort, some of which may be serious. It 
is very important that you understand the risks in this research study before you decide whether you 
will participate. For details and a list of risks you should know about, please see the What Are the 
Risks of Taking Part in the Study section below. 
 
6. Will I be paid to participate? 
Payment for your time or travel is available if you decide that you will take part in this study. For 
more information, please see the What Will I Get for Taking Part in this Study section below.  
 
7. Will it cost me anything to participate? 
There is no cost to you for taking part in this study. 
  
Please review the rest of this document for details about these topics and additional things you 
should know before making a decision about whether you will participate in this research.  
 
INTRODUCTION 
We invite you to take part in a research study about PrEP for Human Immunodeficiency Virus (HIV). 
PrEP is short for Pre-Exposure Prophylaxis. Pre-exposure means before being exposed to HIV. 
Prophylaxis is the way people prevent a disease from infecting them. With PrEP for HIV, medications 
are being developed to prevent people from getting infected if they are exposed to HIV.  
 
This form gives information about what it means to join the study. Please read it and ask any questions 
that you may have. You can take as much time as you need to fully understand the study. We will ask 
questions to see if we have explained the study clearly. After you understand the study, if you decide 
that you will take part, we will ask you to sign and date this form. You will be offered a copy to keep. 
Because you are still a minor, we must have permission from a parent or guardian for you to take part. 
This process is called “informed consent.” 
 
WHAT IS THIS STUDY ABOUT? 
In this study, we want to know if it is safe and acceptable for adolescents who do not have HIV to take 
an anti-HIV drug called cabotegravir (CAB). We would also like to look at the tolerability, or side 
effects, of CAB. CAB is a new drug that is still being studied and is not yet approved by the FDA, or 
U.S. Food and Drug Administration, and is therefore considered experimental. Other studies showed 
that CAB can treat people who have HIV infection and it has recently been shown as a way to prevent 
HIV infection. The only other ways to prevent getting HIV from sex is to use condoms and/or take one 
of two PrEP pills, called Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®) or Tenofovir 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
95 of 152 
2 July 2021 
Alafenamide/Emtricitabine (Trade name: TAF/FTC, Descovy®), every day. But some people have a 
hard time remembering to take a pill every day, so it is a good idea to have other HIV prevention 
options. With CAB, people would get injections every 8 weeks and would not have to remember to take 
a pill every day. It is important that we learn what happens when adolescents use CAB for HIV 
prevention and whether it is safe and acceptable. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov. This Web site will 
not include information that can identify you. At most, the Web site will include a summary of the 
results. You can search this Web site at any time. 
 
DO I HAVE TO JOIN THIS STUDY? 
You do not have to be in this study. The study staff can tell you about other places where you can get the 
care you need even if you do not join the study. If you join the study today, you can still change your 
mind later and leave the study at any time for any reason without penalty. If you decide not to take part 
in this study, you can join another study at a later time if one is available and you qualify for it. 
 
You can’t join this study if you are taking part in another study of drugs, HIV vaccines, or medical 
devices. You must tell the study staff about any other studies you are taking part in or thinking of taking 
part in. This is very important for your safety. [Some sites may have biometric fingerprint screening 
and, if so, sites should add information regarding that here.] 
 
HOW LONG WILL THE STUDY LAST? 
If you decide to join the study, participation will last about 1.5 years and include about 18 study visits at 
this clinic. You will move through the study in 3 steps: 
• Step 1: You will take one CAB pill every day for five weeks 
• Step 2: You will receive a total of 5 CAB injections over 6 months 
• Step 3: You will come to the clinic for study visits for up to one year 
 
WHAT WILL I HAVE TO DO IN THE STUDY? 
If you want to be in this study, you will sign and date this form before you begin the study.  
 
Study Visit Schedule 
• Screening (1 visit) – First, we will find out if you qualify to be in the study.  
• Step 1 (3 visits) – If you qualify and decide to join the study, you will swallow 1 CAB tablet 
every day for 5 weeks starting at the Entry, or Enrollment, Visit. Step 1 is done to make sure 
your body is tolerating the CAB well, so you should take the tablets every day. You will come 
back for a medical check-up at weeks 2 and 4. If Step 1 goes well for you, then you will move to 
Step 2. 
• Step 2 (10 visits) – If you qualify, you will get the first CAB injection at week 5, then again at 
weeks 9, 17, 25 and 33 (5 injection visits). You will come back to the study clinic for a brief 
check-up 1 week after each injection at weeks 6, 10, 18, 26 and 34 (5 safety visits).  
• Step 3 (5 or 6 visits) – After a blood draw 8 weeks after your last injection, you will come to the 
clinic (every 2 or 3 months) for 1 year to check how you are doing and to see how long CAB 
remains in your body after your last injection (+8, +12, +24, +36, +48 weeks). In most people, 
CAB disappears from the body slowly over 6 months, but it may last for a year or so. During this 
Step, you will be provided with Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®) to 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
96 of 152 
2 July 2021 
take daily or continue on CAB LA, so we will be following you to see how well things are going 
on oral PrEP, doing bloodwork, as well as HIV and other STI testing. 
 
You will be in the study for the about 1.5 years. Your parent/guardian does not need to come with you to 
the study visits. The study visits will take from 1 to 4 hours each [sites to modify accordingly]. It is 
important that you attend all of these study visits. If you do not come for a scheduled visit or if a test 
result comes back abnormal, study staff will contact you or visit you. We will ask for your address and 
contact information so that we will be able to get in touch with you. You should not join the study if it’s 
not okay for study staff to contact you and visit you where you stay. If at any time you feel sick, you 
should let the study staff know right away and we may ask you to come back for a check-up.  
 
Study Visit Procedures 
Different procedures are done at different study visits. We will now explain each of the procedures and 
then show you which ones are done at which visits.  
• Physical examinations – We will examine you to check on your health by measuring height, 
weight, temperature and blood pressure. At each study visit, we will check on whether CAB may 
be causing side effects. We will also tell you what to do if you have side effects. 
• Questions – We will ask general questions about your age, living situation, medical health, and 
any medications or vitamins that you take. At some visits, you will also answer questions on a 
computer about your beliefs about HIV, opinions about taking pills and getting injections, sexual 
behavior, and any alcohol or drug use (we call these questions “CASI” for computer-assisted 
self-interview).  
• Counselling – We will discuss ways to protect you from getting HIV and offer condoms. We will 
discuss any challenges you have about taking the CAB pill or attending study visits. 
• CAB pills or injection – During Step 1, we will explain how to take the study pills, watch you 
take a study pill, and explain any side effects the pills may cause. In Step 2 and Step 3 (if 
chosen), the CAB injection will be given into your buttock.  
• Laboratory tests – We will collect blood and urine. Some of these tests are done right away and 
we will tell you the results when they are available. The HIV results will be available before you 
are given CAB each time. Other tests are stored and then done later in a batch. More details are 
shown in the table below this section. Some tests are done in laboratories in other states, so your 
samples may be shipped there for testing. The laboratory tests are done for the following reasons: 
o Blood – To check for infections (HIV, hepatitis B and C, Syphilis), your general health, 
the health of the liver and kidneys, the amount of cholesterol (a fatty substance in your 
blood) and the amount of the study drug that is in your blood. How much blood is taken 
depends on which tests are due at each visit and is between 1 and 4 teaspoons each time 
(5-20mL). Study staff will tell you more about fasting before the cholesterol test. The 
study staff may be required by law to report any positive result of the HIV, Hepatitis, and 
syphilis tests to the local health authority. 
o Urine – To test if there is sugar or protein in your urine and for sexually transmitted 
infections. 
• Hepatitis B vaccination – At Week 2 or soon thereafter, you will be given the hepatitis B 
vaccination if testing shows you are not already immune. Additional vaccination (boosters) will 
be given at approximately Weeks 6 and 33).  
• HIV Prevention –The amount of CAB remaining in the body disappears slowly after you stops 
the CAB injections – it can last in the body for about one year, so you must use other ways of 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
97 of 152 
2 July 2021 
preventing HIV if you are at risk of infection. For this reason, we will offer you 
Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®) tablets as PrEP after you stop the 
CAB injections or allow you to stay on CAB LA injections, if chosen. Before you leave the 
study, we will help you find a place where you can continue getting HIV prevention care [sites to 
add information here or elsewhere in the consent form].  
 
Tables of Study Visit Procedures 
 
Step 1 – to see if your body is tolerating the CAB well 
 
 
screening 
entry 
Week 2 
Week 4 
Receive CAB pills (5 weeks’ worth) 
 
√ 
 
 
Pill count 
 
 
√ 
√ 
Questions/CASI 
√ 
√ 
√ 
√ 
Counselling 
√ 
√ 
√ 
√ 
Physical exam 
√ 
√ 
√ 
√ 
Blood 
√ 
√ 
√ 
√ 
Urine 
√ 
√ 
 
 
Rectal and oral pharyngeal swabs 
√ 
 
 
 
 
Step 2 – to give you the CAB injections and check your health (grey columns mean injection weeks)  
 
 
Week 
5 
Week 
6 
Week 
9 
Week 
10 
Week 
17 
Week 
18 
Week 
25 
Week 
26 
Week 
33 
Week 
34 
Questions/CASI 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
Counselling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Brief physical 
exam 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Blood 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Urine 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Rectal and oral 
pharyngeal 
swabs 
 
 
 
 
√ 
 
 
 
√ 
 
CAB injection 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
PrEP pills 
offered 
 
 
 
 
 
 
 
 
 
√ 
Step 3 drug 
choice 
discussions 
 
 
 
 
 
 
 
 
√ 
√ 
 
Step 3: your choice of moving to oral PrEP or remaining on CAB LA injections. 
 
Step 3-Oral PrEP Follow-Up Visits – to see how long the CAB remains in your body 
 
 
+8 Weeks +12 Weeks +24 Weeks +36 Weeks +48 Weeks 
Questions/CASI 
 
√ 
√ 
√ 
√ 
Counselling 
√ 
√ 
√ 
√ 
√ 
Brief physical exam 
 
√ 
√ 
√ 
√ 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
98 of 152 
2 July 2021 
Blood 
√ 
√ 
√ 
√ 
√ 
Urine 
 
 
√ 
 
√ 
Rectal and oral pharyngeal swabs 
 
 
√ 
 
√ 
PrEP pills offered 
 
√ 
√ 
√ 
 
 
OR: 
 
Step 3-Injection Follow-Up Visits – remain on CAB LA, instead of switching to oral PrEP 
 
 
+8 
Weeks 
+16 
Weeks 
+24 
Weeks 
+32 
Weeks 
+40 
Weeks 
+48 
Weeks 
Questions/CASI 
 
√ 
√ 
√ 
√ 
√ 
Counselling 
√ 
√ 
√ 
√ 
√ 
√ 
Brief physical exam 
 
√ 
√ 
√ 
√ 
√ 
Blood 
√ 
√ 
√ 
√ 
√ 
√ 
Urine 
 
 
√ 
 
 
√ 
Rectal and oral pharyngeal 
swabs 
 
 
√ 
 
 
√ 
CAB LA injections 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
Permanently Stopping Study Drug 
CAB pills are only given in Step 1, and then stopped permanently. If you need to leave the study before 
you receive any CAB injections, we’d still like to do a final study visit, which will include the same 
activities as the Step 3 Follow-Up Visits. If you permanently stop taking CAB after you had at least 1 
CAB injection, then you will move straight to Step 3 follow-up visits, if you agree to stay in the study. If 
you choose oral PrEP for Step 3, then 3 months’ supply of Truvada will be provided at Week 34. 
 
WHAT IF I BECOME INFECTED WITH HIV? 
Being in this study will not cause HIV infection, but you could become infected with HIV through sex 
or other activities while in this study. If you get HIV infection in Step 1, you will stop using oral CAB 
and exit the study, but if you get HIV infection in Steps 2 or 3, you will continue on study with no 
injections,  to make sure that you are doing okay. The study staff will counsel you and refer you for HIV 
treatment and other available services, but the study will not pay for this treatment. We will share any 
test results that will help you get the treatment you need. Testing, which will take an additional 1-3 mL 
of blood, will be done to see if your HIV is resistant to any drugs that are used to treat HIV infection. 
This testing will help select the best drugs to treat your HIV infection. 
 
Tables of Study Visit Procedures if you become infected with HIV during Step 2 or Step 3 
If you become infected with HIV infection before your first injection, you will have the oral CAB 
stopped permanently and will be referred to local HIV-related care and exit from the study. 
 
HIV 
Confirmation 
Visit 
+12 
weeks 
+24 weeks 
+36 weeks 
+48 weeks 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
99 of 152 
2 July 2021 
 
WHAT OTHER TESTS WILL BE DONE? 
After all the laboratory tests mentioned above for this study have been done, there may be some of your 
samples left over. We want to keep these in storage for future tests related to HIV and other infections, 
including testing for the drugs used in this study and other anti-HIV medications, or tests about your 
genes. There is a separate form with more information about this. We will not use DNA from your 
stored samples to study your whole genetic sequence (also called your "genome"). If you agree to this 
future research, identifiers might be removed from your identifiable private information or identifiable 
biospecimens collected during this study. That information could then be used for future research studies 
or distributed to another investigator for future research studies without additional informed consent. 
 
WHAT ARE THE RISKS OF TAKING PART IN THIS STUDY? 
Taking part in this study may involve some risks and discomfort. 
 
Risk from Blood Draws – The needle can cause pain, swelling, bruising, or bleeding from the needle 
site. Drawing blood can cause fainting or infection, but this is very rare. 
 
Risk from Receiving CAB Injections – People who got CAB injections in other studies had pain, skin 
irritation, skin redness, bumps, swelling, itching, or bruising at the spot where they got the shot. Most 
reactions go away in a week or less but sometimes they can last a long time. The injection could be 
given too deeply or not deeply enough, missing the muscle and entering your skin, blood, or a nerve. 
Everything possible will be done to decrease this risk, including watching you for problems during the 
study. If we think that the injection was not given the right way, you might be asked to stay in the clinic 
up to 2 hours after the injection to watch how you are doing. Receiving injections can cause some 
people to feel lightheaded or feel like they might pass out, or 'faint'. This is called a 'vasovagal reaction' 
and it can occur with many medical procedures but usually resolves quickly. 
 
Risk of CAB Side Effects – All drugs can cause side effects. Some side effects are minor; others can be 
severe. Some side effects are common; others are rare. Some people who take the study drug have some 
of the side effects. Other people have different side effects, or no side effects. The most common side 
effects for CAB are listed below. It is not known if CAB, other drugs or the participant’s other health 
problems caused these side effects. There may be other side effects that we do not know about now. This 
may be especially true for adolescents, because this is the first study of CAB in adolescents.  
  
Very Common Side Effects of CAB 
Common Side Effects of CAB 
Questions/CASI 
√ 
√ 
√ 
√ 
√ 
Counselling  
√ 
 
 
 
 
Brief physical exam 
√ 
√ 
√ 
√ 
√ 
Blood  
√ 
√ 
√ 
√ 
√ 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
100 of 152 
2 July 2021 
• Nausea (feeling sick to the stomach) 
• Diarrhea or loose stools 
• Runny nose, sore throat/Upper 
respiratory tract infection 
• Headache 
• Fever 
• Lack of energy 
 
• Rash 
• Itching  
• Vomiting (being sick) 
• Stomach pain and discomfort  
• Problems sleeping  
• Abnormal dreams/nightmares 
• Feeling light headed 
• Depression 
• Passing gas or wind 
• Joint or muscle pain 
• Increase in the level of enzymes made in the muscles 
(creatine phosphokinase) 
 
Some of the people who received CAB in other studies also had abnormal liver tests. In most people, 
this was explained by other things such as a new virus infection with Hepatitis. Very few people did not 
have another possible reason, so it is possible that a mild form of liver damage happened from taking 
CAB. In those people, the liver tests got better after stopping CAB, showing that any damage was 
temporary. Seizures have been seen (rarely) in people who had CAB. They are not thought to be caused 
by CAB, but the study staff will ask you about them. We have an information sheet about CAB and its 
side effects for you to keep. 
 
Allergic Reaction Risks – As with taking any drug, there is a risk of allergic reaction.  If you have a very 
serious allergic reaction, you may be at risk of death.  Some symptoms of allergic reactions are: 
• Rash 
• Wheezing and difficulty breathing 
• Dizziness and fainting 
• Swelling around the mouth, throat or eyes 
• A fast pulse 
• Sweating 
 
Please seek treatment immediately and tell the study doctor and study staff if you have any of these 
symptoms. 
 
Risk of HIV Resistance to CAB – We do not know if using CAB for PrEP will mean that CAB will not 
work to treat the HIV if you get infected with HIV during the study or in the future (this is called drug 
resistance). Drug resistance usually occurs when the amount of a drug in the body is too low to kill the 
virus. You will have low levels of CAB in the body for about one year after the last injection, or if you 
don’t get the injections when they are due. This is why it is very important that you use other methods to 
protect against HIV infection whenever you are at risk, like using condoms and, if you are no longer 
receiving CAB, using Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®) PrEP pills.  
 
Risks potentially related to Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®) for PrEP - Like 
all other drugs, you may have symptoms or side effects while taking PrEP. These symptoms or side 
effects may be due to participation in the study or due to illnesses that have no relation to the study, like 
a cold or flu. You should tell the study staff at the study clinic about any symptoms that you feel while 
you are participating in the study. In past PrEP research studies, nausea and diarrhea were the most 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
101 of 152 
2 July 2021 
common side effects, and happened in about 10% or 1 in 10 people. Nausea and diarrhea mainly 
happened in the first month and then went away. A small number (less than 1% or 1 out of 100 people) 
in PrEP studies showed a small decrease in how their kidneys work, but this stopped when the people 
stopped taking the study drug. Other side effects were very rare and usually resolved when the study 
drug was stopped.  
 
Risks of Asking Sensitive Questions – You may feel uncomfortable when we ask personal questions. 
You do not have to answer any question that you do not want to and you can stop answering the 
questions at any time.  
 
Risk of Disclosure of Private Information – We will make every effort to keep your information private 
and confidential. It is possible that others may learn that you are part of this study and they may think 
that you are infected with HIV or are at high risk for HIV. Because of this you may feel stigma, stress or 
embarrassment. We will not share any information about you or your health with anyone, even your 
parent/guardian, without talking to you first, except when [sites to insert relevant information about any 
legal obligations for disclosure, for example…your life is thought to be in danger]. 
 
Risks of Rectal Swabs – You may have mild discomfort when the swab is performed, particularly if you 
have hemorrhoids. In some cases, a very small amount of bleeding may occur. If you are already having 
pain in the rectal area, be sure to let the study staff know. 
 
Risks of Oral Pharyngeal Swabs – There are no risks or complications associated with this collection 
procedure. The procedure may cause momentary gagging because the back of the throat is a sensitive 
area, but it shouldn’t be painful.  
 
Other Risks – There may be uncommon or previously unknown risks that might occur. You should 
report any problems to the study staff immediately. 
 
WHAT ARE THE BENEFITS OF TAKING PART IN THIS STUDY? 
You may get direct benefit from being in this study. CAB LA has been shown to prevent HIV infections 
among adult men and transgender women. You will get information about your health and the results of 
the tests, as well as treatment for sexually transmitted infections. The counseling you get during this 
study may help you avoid HIV and other sexually transmitted infections. You or others in your 
community may benefit from this study later. The information gathered during this study may help to 
prevent the spread of HIV. This may be beneficial to you and your community.  
 
ARE THERE ANY COSTS TO ME FOR TAKING PART IN THIS STUDY? 
You will pay no money to be in the study. The study drug CAB will be provided and study procedures 
will be performed at no additional cost to you and/or your insurance company.  
 
WHAT OTHER CHOICES DO I HAVE? 
It is possible that Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®) or Tenofovir 
Alafenamide/Emtricitabine (Trade name: TAF/FTC, Descovy®) for PrEP are available in your local 
area for HIV prevention. If you prefer to take PrEP instead of joining the study, ask the study staff to 
refer you for HIV prevention medical services.  
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
102 of 152 
2 July 2021 
[Sites to include/amend the following if applicable: There may be other studies going on here or in the 
community that you may be eligible for. If you wish, we will tell you about other studies that we know 
about. There also may be other places where you can go for HIV counseling and testing. We will tell you 
about those places if you wish.] 
 
WILL I BE TOLD IF THERE IS NEW INFORMATION? 
You will be told about any new information learned during the course of the study that might cause you 
to change your mind about being in the study. At the end of the study, you will be told when study 
results may be available and how we will let you know about the results. 
 
COMMERCIAL PROFIT 
Your biospecimens collected during this study will not be used for commercial profit. 
 
CLINICALLY RELEVANT RESULTS  
Research results that are clinically relevant, including individual research results, will be disclosed to 
you under these conditions:  
• HIV diagnostic testing results 
• Any results that affect the treatment of HIV  
 
ARE THERE ANY REASONS WHY I MAY BE ASKED TO STOP TAKING PART IN THIS 
STUDY? 
You may be withdrawn from the study if any of the following occur:  
• Your parent/guardian decides that they do not want you to participate anymore (if still under the 
legal age of consent). 
• You are unable or unwilling to attend clinic visits and/or follow all of the study procedures or 
instructions.  
• You could be harmed by continuing to take the pills or getting an injection. 
• The study is stopped or canceled. 
• The study doctor feels that staying in the study would be harmful to you. 
• Other reasons, as decided by the study staff.  
 
WHAT WILL I GET FOR TAKING PART IN THIS STUDY? 
 
You will be paid up to a total of $xx.xx if you complete this study. You will be paid for the visits you 
complete according to the following schedule: 
• $xx.xx for Visits xxx.  
• $xx.xx for Visits xxx.  
• $xx.xx for Visits xxx.  
 
If you do not complete the study, for any reason, you will be paid for each study visit you do complete.  
 
You will be paid ___________ [“after each visit,” “annually,” “bi-weekly,” etc.] 
 
If you have any questions regarding your compensation for participation, please contact the study staff.   
 
HOW WILL MY PRIVACY BE PROTECTED? 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
103 of 152 
2 July 2021 
To keep your information private, your samples will be labeled with a code that can only be traced back 
to the study clinic. Your name, where you live, and other personal information will be protected by the 
study clinic. The results of any tests done will not be included in your health records without your 
permission. Every effort will be made to keep your personal information confidential, but we cannot 
guarantee absolute confidentiality. Your records may be reviewed, under guidelines of the United States 
Federal Privacy Act, by the United States Food and Drug Administration (FDA); the sponsor of the 
study (United States National Institutes of Health [NIH]), other US, local and international regulatory 
entities may also review your study records, as well as the Advarra Institutional Review Board (IRB), 
Ethics Committees (EC), study staff, study monitors, the company that makes CAB, and other local 
authorities. Groups that oversee the study include:  
• Advarra IRB 
• [insert name of other site regulatory entities] 
• Representatives of the HPTN  
• The United States National Institutes of Health and its study monitors (including NICHD and its 
monitor, Westat) 
• The United States Food and Drug Administration 
• The United States Office for Human Research Protections 
• Other U.S., local, and international regulatory entities 
• ViiV Healthcare (the company that makes CAB) 
 
The study staff and these groups are required to keep study records private and confidential. The results 
of the study may be presented publicly or published. However, no presentation or publication will use 
your name or identify you personally. Your study information may be given to other authorities if 
required by law, including diagnoses of sexually transmitted infections. For example, we are required to 
follow state laws and report any risk of harm to you or others. This would include sexual activity with an 
adult while you are a minor. 
 
In addition to the efforts made by the study staff to help keep your personal information confidential, we 
have obtained a Certificate of Confidentiality from the U.S. Federal Government. This Certificate 
protects researchers from being forced to tell people who are not connected with this study about your 
participation. The Certificate of Confidentiality does not prevent you from releasing information about 
yourself and your participation in the study. The Certificate cannot be used to resist a demand for 
information from personnel of the United States Government that is used for auditing or evaluation of 
federally funded projects or for information that must be disclosed in order to meet the requirements of 
the federal Food and Drug Administration (FDA). Even with the Certificate of Confidentiality, if the 
study staff learns of possible child abuse and/or neglect or a risk of harm to you or others, we will tell 
the proper authorities. 
 
WHAT HAPPENS IF I AM INJURED DURING THE STUDY? 
Your health is important to us. We will make every effort to protect your well-being and minimize risks. 
It is possible, however, that you could have an illness or injury that is study-related. This means that the 
illness or injury occurred as a direct result of the study procedures or the study drug.  
 
If a study-related illness or injury occurs, we will treat you or tell you where you can get treatment. The 
cost for this treatment may be charged to you or your insurance company. There is no program for 
compensation either through the study site or the U.S. National Institutes of Health. 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
104 of 152 
2 July 2021 
 
By signing and dating this document, you will not lose any of your legal rights or release anyone 
involved in the research from responsibility for mistakes. 
 
WHOM TO CONTACT ABOUT THIS STUDY 
During the study, if you experience any medical problems, suffer a research-related injury, or have 
questions, concerns or complaints about the study, please contact the study doctor at the telephone 
number listed on the first page of this consent document. If you seek emergency care, or hospitalization 
is required, alert the treating physician that you are participating in this research study.  
 
An institutional review board (IRB) is an independent committee established to help protect the rights of 
research participants. If you have any questions about your rights as a research participant, and/or 
concerns or complaints regarding this research study, contact: 
 
• By mail: 
Study Subject Adviser 
Advarra IRB 
6940 Columbia Gateway Drive, Suite 110 
Columbia, MD 21046 
• or call toll free:    877-992-4724 
• or by email:          adviser@advarra.com 
 
Please reference the following number when contacting the Study Subject Adviser: Pro00040790. 
 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
105 of 152 
2 July 2021 
SCREENING AND ENROLLMENT CONSENT 
 
Your signature and date on this form means that: 
• You understand the information given to you in this form,  
• You accept the provisions in the form, on behalf of your child, and  
• You agree to permit your child to join the study  
 
You will not give up any of you or your child’s legal rights by signing and dating this consent form. 
 
CONSENT FOR MINOR TO TAKE PART IN THIS STUDY 
In consideration of all of the above, I give my consent for my child to participate in this research study. I 
will be given a copy of this document to keep for my records. I agree to let my child take part in this 
study. 
 
______________________________ 
 
Name of Participant (print) 
 
 
 
 
 
 
 
 
 
PARENT/GUARDIAN INFORMED CONSENT                
 
________________________ 
Relationship to participant 
 
 
 
 
 
 
 
____________________________________ 
Name (print)  
 
 
 
Signature and Date 
 
ASSENT TO TAKE PART IN THIS STUDY FOR ADOLESCENT PARTICIPANTS AGES 14 
YEARS – AGE OF MAJORITY 
I have read this form. I know that this is a research study. I have been told about the risks and potential 
benefits of taking part in the study. I have asked all the questions I have about the study and have gotten 
answers to my questions. I know that I am free to quit the study at any time without any penalties or loss 
of benefits. I will tell the study doctor, the study staff or my parent(s)/guardian(s), if I choose to stop the 
study so that I can stop in the best way to not harm my health. I will be given a signed and dated copy of 
this form to keep.  
 
I agree to take part in this research study. 
 
 
 
 
 
 
 
____________________________________ 
Participant’s Name (print) 
 
 
Signature and Date 
 
 
 
 
 
 
 
 
____________________________________ 
Study Staff Conducting 
 
 
Study Staff Signature and Date 
Consent Discussion (print) 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
106 of 152 
2 July 2021 
12.8 
APPENDIX VIII: INFORMED CONSENT FOR ADOLESCENT PARTICIPANTS 
ABLE TO CONSENT FOR THEMSELVES (SELF-CONSENT) AND PARTICIPANTS WHO 
REACH THE AGE OF MAJORITY 
 
 
Sponsor / Study Title: 
  
Division of AIDS (DAIDS), United States (US) National 
Institute of Allergy and Infectious Diseases (NIAID), Eunice 
Kennedy Shriver National Institute of Child Health and 
Human Development (NICHD), US National Institutes of 
Health (NIH) / “HPTN 083-01: Safety, Tolerability and 
Acceptability of Long-Acting Cabotegravir (CAB LA) for 
the Prevention of HIV among Adolescent Males – A sub-
study of HPTN 083” 
 
Protocol Number: 
 
HPTN 083-01 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
 
 
Key Information: 
 
The first two pages of this document include summary information about this study that will help 
you decide whether or not you should participate. More detailed information is provided after this 
summary section. 
 
 
About this research  
You are being asked to join a research study. Scientists do research to answer important questions which 
might help change or improve the way we do things in the future. This form explains the research study 
and your part in the study. Please read it carefully and take as much time as you need. Ask your study 
doctor or the study team to explain any words or information that you do not understand. You may take 
this description home and discuss it with your family or friends to help you decide.  
 
Taking part in this research study is voluntary 
You may choose not to take part in the study or may choose to leave the study at any time. Deciding not 
to participate, or deciding to leave the study later, will not result in any penalty or loss of benefits to 
which you are entitled and will not affect your relationship with the study site. 
 
Important Information  


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
107 of 152 
2 July 2021 
This information gives you an overview of the research. More information about these topics may be 
found in the pages that follow.  
 
1. Why is this research being done? 
There is a new drug called cabotegravir (CAB) that can treat people who have human 
immunodeficiency virus (HIV) infection. CAB is also being tested to see if it can protect people 
from getting HIV and has been found to be effective at preventing HIV among adult men and 
transgender women. In this study, we want to know if it is safe and acceptable for adolescents who 
do not have HIV to take CAB. For more information, please see the What is this Study About section 
below.  
 
2. What will happen to me during the study? 
You will move through the study in 3 steps: 
• Step 1: You will take one CAB pill every day for five weeks 
• Step 2: You will receive a total of 5 CAB injections over 6 months 
• Step 3: You will come to the clinic for study visits for up to one year. 
 
Different procedures are done at different study visits. The procedures include: 
• Physical examinations – We will examine you to check on your health by measuring height, 
weight, temperature and blood pressure.  
• Questions – We will ask general questions about your age, living situation, medical health, 
and as well as beliefs about HIV, opinions about taking pills and getting injections, sexual 
behavior, and any alcohol or drug use. 
• Counselling – We will discuss ways to protect you from getting HIV and offer condoms. We 
will discuss any challenges you have taking the CAB pill or attending study visits. 
• CAB pills or injection – During Step 1, we will explain how to take the study pills, watch you 
take a study pill, and explain any side effects the pills may cause. In Steps 2 and 3, if you 
decide to stay on CAB LA, the CAB injection will be given into your buttock.  
• Laboratory tests – We will collect blood, urine, rectal swabs, and oral pharyngeal swabs to 
test for HIV, Hepatitis, liver and kidney health, cholesterol, and sexually transmitted 
infections (STIs). If you have an STI, you will be told so, and referred for appropriate 
treatment. 
• HIV Prevention – We will offer you Tenofovir/Emtricitabine (Trade name: TDF/FTC, 
Truvada®) tablets as pre-exposure prophylaxis (PrEP) after you stop the CAB injections. 
You may, instead, choose to remain on CAB LA injections. 
 
For more information on each procedure and when it happens, please see the What Will I have to Do 
in the Study section below.  
 
3. How long will I participate in the study? 
If you decide to join the study, participation will last about 1.5 years and include a maximum of 18 
study visits at this clinic. If you reach the age of majority while already on study, you will continue 
participation along your original schedule (and not a new 1.5 years). 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
108 of 152 
2 July 2021 
4. Will I benefit from the study? 
It is possible that you may benefit from taking part in this study. The study drug being used has been 
shown to prevent HIV infections among some adults. You will get information about your health and 
the results of the tests, as well as treatment for sexually transmitted infections. The counseling you 
get during this study may help you avoid HIV and other sexually transmitted infections. For more 
information, please see the What are the Potential Benefits of Taking Part in the Study section 
below.  
 
5. Will taking part in the study expose me to risks? 
Taking part in this research may expose you to risks. We may not know or understand all the risks at 
this time. Some people may experience side effects or discomfort, some of which may be serious. It 
is very important that you understand the risks in this research study before you decide whether you 
will participate. For details and a list of risks you should know about, please see the What Are the 
Risks of Taking Part in the Study section below. 
 
6. Will I be paid to participate? 
Payment for your time or travel is available if you decide that you will take part in this study. For 
more information, please see the What Will I Get for Taking Part in this Study section below.  
 
7. Will it cost me anything to participate? 
There is no cost to you for taking part in this study. 
  
Please review the rest of this document for details about these topics and additional things you 
should know before making a decision about whether you will participate in this research.  
 
INTRODUCTION 
We invite you to take part in a research study about PrEP for Human Immunodeficiency Virus (HIV). 
PrEP is short for Pre-Exposure Prophylaxis. Pre-exposure means before being exposed to HIV. 
Prophylaxis is the way people prevent a disease from infecting them. With PrEP for HIV, medications 
are being developed to prevent people from getting infected if they are exposed to HIV.  
 
This form gives information about what it means to join the study. Please read it and ask any questions 
that you may have. You can take as much time as you need to fully understand the study. We will ask 
questions to see if we have explained the study clearly. After you understand the study, if you decide 
that you will take part, we will ask you to sign and date this form. You will be offered a copy to keep. 
This process is called “informed consent.” 
 
WHAT IS THIS STUDY ABOUT? 
In this study, we want to know if it is safe and acceptable for adolescents who do not have HIV to take 
an anti-HIV drug called cabotegravir (CAB). We would also like to look at the tolerability, or side 
effects, of CAB. CAB is a new drug that is still being studied and is not yet approved by the FDA, or 
U.S. Food and Drug Administration. Other studies showed that CAB can treat people who have HIV 
infection, and it has recently been shown as a way to protect people from getting HIV. First, we must 
study if CAB is safe for people who do not have HIV. CAB comes in the form of a pill and also as an 
injection. CAB pills and injections are not yet approved for the treatment or prevention of HIV infection 
by the United States Food and Drug Administration (FDA) and are therefore considered experimental. 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
109 of 152 
2 July 2021 
Recently, the FDA asked for more information about how the CAB pills and injections are manufactured 
and agreed that studies that investigate CAB should continue while they complete their review.  
 
You are being invited to join this study because you live in the United States, where 21% of new HIV 
infections occur among young people ages 13 to 24. Most of these infections occur due to sexual activity 
and about half of the youth who have HIV don’t know it. This study will be offered to about 50 young 
men under 18 years old across several study sites in the US. The person in charge of the study at the 
study site is listed on the first page of this form. The United States National Institutes of Health is paying 
for the study. 
 
Some of the questions that we want to answer with this study are: 
Is it safe for adolescents to take CAB pills and CAB injections? 
Is it acceptable and tolerable for adolescents to use CAB for HIV prevention? 
Are adolescents able to make it to the clinic for injection appointments? 
What do parents/guardians think about their sons using CAB for HIV prevention? (if applicable) 
 
This study will not show us if CAB prevents new infections with HIV. There are other studies being 
done that will answer that question, but those studies only involve adults. Currently, the only known 
way to prevent HIV infection from sex is to use condoms and/or take one of the two PrEP pills available 
called Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®) or Tenofovir 
Alafenamide/Emtricitabine (Trade name: TAF/FTC, Descovy®) every day. But some people have a 
hard time remembering to take a pill every day, so it is a good idea to have other HIV prevention 
options. With CAB, people would get injections every 8 weeks and would not have to remember to take 
a pill every day. It is important that we learn what happens when adolescents use CAB for HIV 
prevention and whether it is safe and acceptable. 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov. This Web site will 
not include information that can identify you. At most, the Web site will include a summary of the 
results. You can search this Web site at any time. 
 
DO I HAVE TO JOIN THIS STUDY? 
You do not have to be in this study. The study staff can tell you about other places where you can get the 
care you need even if you do not join the study. If you join the study today, you can still change your 
mind later and leave the study at any time for any reason without penalty. If you decide not to take part 
in this study, you can join another study at a later time if one is available and you qualify for it. 
 
You can’t join this study if you are taking part in another study of drugs, HIV vaccines, or medical 
devices. You must tell the study staff about any other studies you are taking part in or thinking of taking 
part in. This is very important for your safety. [Some sites may have biometric fingerprint screening 
and, if so, sites should add information regarding that here.] 
 
HOW LONG WILL THE STUDY LAST? 
If you decide to join the study, participation will last about 1.5 years and include about 18 study visits at 
this clinic. You will move through the study in 3 steps: 
Step 1: You will take one CAB pill every day for five weeks 
Step 2: You will receive a total of 5 CAB injections over approximately 6 months 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
110 of 152 
2 July 2021 
Step 3: You will come to the clinic for study visits for up to one year 
 
WHAT WILL I HAVE TO DO IN THE STUDY? 
If you want to be in this study, you will sign and date this form before you begin the study.  
 
Study Visit Schedule 
Screening (1 visit) – First, we will find out if you qualify to be in the study.  
Step 1 (3 visits) – If you qualify and decide to join the study, you will swallow 1 CAB tablet every 
day for 5 weeks starting at the Entry, or Enrollment, Visit. Step 1 is done to make sure your body 
is tolerating the CAB well, so you should take the tablets every day. You will come back for a 
medical check-up at weeks 2 and 4. If Step 1 goes well for you, then you will move to Step 2. 
Step 2 (10 visits) – If you qualify, you will get the first CAB injection at week 5, then again at weeks 
9, 17, 25 and 33 (5 injection visits). You will come back to the study clinic for a brief check-up 1 
week after each injection at weeks 6, 10, 18, 26 and 34 (5 safety visits).  
Step 3 (5 or 6 visits) – After a blood draw 8 weeks after your last injection, you will come to the 
clinic (every 2 or 3 months) for 1 year to check how you are doing and to see how long CAB 
remains in your body after your last injection (+8, +12, +24, +36, +48 weeks). In most people, 
CAB disappears from the body slowly over 6 months, but it may last for a year or so. During this 
Step, you will be provided with Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®) to 
take daily or have the opportunity to continue on CAB LA injections, so we will be following 
you to see how well things are going, doing bloodwork, as well as HIV and other STI testing. 
 
You will be in the study for the about 1.5 years. The study visits will take from 1 to 4 hours each [sites 
to modify accordingly]. It is important that you attend all of these study visits. If you do not come for a 
scheduled visit or if a test result comes back abnormal, study staff will contact you or visit you. We will 
ask for your address and contact information so that we will be able to get in touch with you. You 
should not join the study if it’s not okay for study staff to contact you and visit you where you stay. If at 
any time you feel sick, you should let the study staff know right away and we may ask you to come back 
for a check-up.  
 
Study Visit Procedures 
Different procedures are done at different study visits. We will now explain each of the procedures and 
then show you which ones are done at which visits.  
Physical examinations – We will examine you to check on your health by measuring height, weight, 
temperature and blood pressure. At each study visit, we will check on whether CAB may be 
causing side effects. We will also tell you what to do if you have side effects. 
Questions – We will ask general questions about your age, living situation, medical health, and any 
medications or vitamins that you take. At some visits, you will also answer questions on a 
computer about your beliefs about HIV, opinions about taking pills and getting injections, sexual 
behavior, and any alcohol or drug use (we call these questions “CASI” for computer-assisted 
self-interview).  
Counselling – We will discuss ways to protect you from getting HIV and offer condoms. We will 
discuss any challenges you have about taking the CAB pill or attending study visits. 
CAB pills or injection – During Step 1, we will explain how to take the study pills, watch you take a 
study pill, and explain any side effects the pills may cause. In Steps 2 and 3, if you decide to stay 
on CAB LA, the CAB injection will be given into your buttock.  


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
111 of 152 
2 July 2021 
Laboratory tests – We will collect blood and urine. Some of these tests are done right away and we 
will tell you the results when they are available. The HIV results will be available before you are 
given CAB each time. Other tests are stored and then done later in a batch. More details are 
shown in the table below this section. Some tests are done in laboratories in other states, so your 
samples may be shipped there for testing. The laboratory tests are done for the following reasons: 
Blood – To check for infections (HIV, hepatitis B and C, Syphilis), your general health, the 
health of the liver and kidneys, the amount of cholesterol (a fatty substance in your 
blood) and the amount of the study drug that is in your blood. How much blood is taken 
depends on which tests are due at each visit and is between 1 and 4 teaspoons each time 
(5-20mL). Study staff will tell you more about fasting before the cholesterol test. The 
study staff may be required by law to report any positive results of the HIV, Hepatitis, 
and syphilis tests to the local health authority.  
Urine – To test if there is sugar or protein in your urine and for sexually transmitted 
infections. 
Hepatitis B vaccination – At Week 2 or soon thereafter, you will be given the hepatitis B vaccination 
if testing shows you are not already immune. Additional vaccination (boosters) will be given at 
approximately Weeks 6 and 33).  
HIV Prevention – We do not know for sure if CAB will protect you from getting HIV. Also, the 
amount of CAB remaining in the body disappears slowly after you stops the CAB injections – it 
can last in the body for about one year, so you must use other ways of preventing HIV if you are 
at risk of infection. For this reason, we will offer you Tenofovir/Emtricitabine (Trade name: 
TDF/FTC, Truvada®) tablets as PrEP after you stop the CAB injections or allow you to stay on 
CAB LA injections, if chosen. Before you leave the study, we will help you find a place where 
you can continue getting HIV prevention care [sites to add information here or elsewhere in the 
consent form].  
 
Tables of Study Visit Procedures 
 
Step 1 – to see if your body is tolerating the CAB well 
 
 
screening 
entry 
Week 2 
Week 4 
Receive CAB pills (5 weeks’ worth) 
 
√ 
 
 
Pill count 
 
 
√ 
√ 
Questions/CASI 
√ 
√ 
√ 
√ 
Counselling 
√ 
√ 
√ 
√ 
Physical exam 
√ 
√ 
√ 
√ 
Blood 
√ 
√ 
√ 
√ 
Urine 
√ 
√ 
 
 
Rectal and oral pharyngeal swabs 
√ 
 
 
 
 
Step 2 – to give you the CAB injections and check your health (grey columns mean injection weeks)  
 
 
Week 
5 
Week 
6 
Week 
9 
Week 
10 
Week 
17 
Week 
18 
Week 
25 
Week 
26 
Week 
33 
Week 
34 
Questions/CASI 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
Counselling 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
112 of 152 
2 July 2021 
Brief physical 
exam 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Blood 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Urine 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Rectal and oral 
pharyngeal 
swabs 
 
 
 
 
√ 
 
 
 
√ 
 
CAB injection 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
Step 3 drug 
choice 
discussions 
 
 
 
 
 
 
 
 
√ 
√ 
 
Step 3: your choice of moving to oral PrEP or remaining on CAB LA injections. 
 
Step 3- Oral PrEP Follow-Up Visits – to see how long the CAB remains in your body 
 
 
+8 Weeks +12 Weeks +24 Weeks +36 Weeks +48 Weeks 
Questions/CASI 
 
√ 
√ 
√ 
√ 
Counselling 
√ 
√ 
√ 
√ 
√ 
Brief physical exam 
 
√ 
√ 
√ 
√ 
Blood 
√ 
√ 
√ 
√ 
√ 
Urine 
 
 
√ 
 
√ 
Rectal and oral pharyngeal swabs 
 
 
√ 
 
√ 
PrEP pills offered 
 
√ 
√ 
√ 
 
 
OR: 
 
Step 3-Injection Follow-Up Visits – remain on CAB LA, instead of switching to oral PrEP 
 
 
+8 
Weeks 
+16 
Weeks 
+24 
Weeks 
+32 
Weeks 
+40 
Weeks 
+48 
Weeks 
Questions/CASI 
 
√ 
√ 
√ 
√ 
√ 
Counselling 
√ 
√ 
√ 
√ 
√ 
√ 
Brief physical exam 
 
√ 
√ 
√ 
√ 
√ 
Blood 
√ 
√ 
√ 
√ 
√ 
√ 
Urine 
 
 
√ 
 
 
√ 
Rectal and oral pharyngeal 
swabs 
 
 
√ 
 
 
√ 
CAB LA injections 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
Permanently Stopping Study Drug 
CAB pills are only given in Step 1, and then stopped permanently. If you need to leave the study before 
you receive any CAB injections, we’d still like to do a final study visit, which will include the same 
activities as the Step 3 Follow-Up Visits. If you permanently stop taking CAB after you had at least 1 
CAB injection, then you will move straight to Step 3 follow-up visits, if you agree to stay in the study. If 
you choose oral PrEP for Step 3, then 3 months’ supply of Truvada will be provided at Week 34. 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
113 of 152 
2 July 2021 
WHAT IF I BECOME INFECTED WITH HIV? 
Being in this study will not cause HIV infection, but you could become infected with HIV through sex 
or other activities while in this study. If you get HIV infection in Step 1, you will stop using oral CAB 
and exit the study, but if you get HIV infection in Steps 2 or 3, you will continue on study with no 
injections, to make sure that you are doing okay. The study staff will counsel you and refer you for HIV 
treatment and other available services, but the study will not pay for this treatment. We will share any 
test results that will help you get the treatment you need. Testing, which will take an additional 1-3 mL 
of blood, will be done to see if your HIV is resistant to any drugs that are used to treat HIV infection. 
This testing will help select the best drugs to treat your HIV infection. 
 
Tables of Study Visit Procedures if you become infected with HIV during Step 2 or Step 3 
If you become infected with HIV infection before your first injection, you will have the oral CAB 
stopped permanently and will be referred to local HIV-related care and exit from the study. 
 
 
WHAT OTHER TESTS WILL BE DONE? 
After all the laboratory tests mentioned above for this study have been done, there may be some of your 
samples left over. We want to keep these in storage for future tests related to HIV and other infections, 
including testing for the drugs used in this study and other anti-HIV medications, or tests about your 
genes. There is a separate form with more information about this. We will not use DNA from your 
stored samples to study your whole genetic sequence (also called your "genome"). If you agree to this 
future research, identifiers might be removed from your identifiable private information or identifiable 
biospecimens collected during this study. That information could then be used for future research studies 
or distributed to another investigator for future research studies without additional informed consent. 
 
WHAT ARE THE RISKS OF TAKING PART IN THIS STUDY? 
Taking part in this study may involve some risks and discomfort. 
 
Risk from Blood Draws – The needle can cause pain, swelling, bruising, or bleeding from the needle 
site. Drawing blood can cause fainting or infection, but this is very rare. 
 
Risk from Receiving CAB Injections – People who got CAB injections in other studies had pain, skin 
irritation, skin redness, bumps, swelling, itching, or bruising at the spot where they got the shot. Most 
reactions go away in a week or less but sometimes they can last a long time. The injection could be 
given too deeply or not deeply enough, missing the muscle and entering your skin, blood, or a nerve. 
Everything possible will be done to decrease this risk, including watching you for problems during the 
study. If we think that the injection was not given the right way, you might be asked to stay in the clinic 
up to 2 hours after the injection to watch how you are doing. Receiving injections can cause some 
HIV 
Confirmation 
Visit 
+12 
weeks 
+24 weeks 
+36 weeks 
+48 weeks 
Questions/CASI 
√ 
√ 
√ 
√ 
√ 
Counselling  
√ 
 
 
 
 
Brief physical exam 
√ 
√ 
√ 
√ 
√ 
Blood  
√ 
√ 
√ 
√ 
√ 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
114 of 152 
2 July 2021 
people to feel lightheaded or feel like they might pass out, or 'faint'. This is called a 'vasovagal reaction' 
and it can occur with many medical procedures but usually resolves quickly. 
 
Risk of CAB Side Effects – All drugs can cause side effects. Some side effects are minor; others can be 
severe. Some side effects are common; others are rare. Some people who take the study drug have some 
of the side effects. Other people have different side effects, or no side effects. The most common side 
effects for CAB are listed below. It is not known if CAB, other drugs or the participant’s other health 
problems caused these side effects. There may be other side effects that we do not know about now. This 
may be especially true for adolescents, because this is the first study of CAB in adolescents.  
  
Very Common Side Effects of CAB 
Common Side Effects of CAB 
• Nausea (feeling sick to the stomach) 
• Diarrhea or loose stools 
• Runny nose, sore throat/Upper 
respiratory tract infection 
• Headache 
• Fever 
• Lack of energy 
 
• Rash 
• Itching  
• Vomiting (being sick) 
• Stomach pain and discomfort  
• Problems sleeping  
• Abnormal dreams/nightmares 
• Feeling light headed 
• Depression 
• Passing gas or wind 
• Joint or muscle pain 
• Increase in the level of enzymes made in the muscles 
(creatine phosphokinase) 
 
Some of the people who received CAB in other studies also had abnormal liver tests. In most people, 
this was explained by other things such as a new virus infection with Hepatitis. Very few people did not 
have another possible reason, so it is possible that a mild form of liver damage happened from taking 
CAB. In those people, the liver tests got better after stopping CAB, showing that any damage was 
temporary. Seizures have been seen (rarely) in people who had CAB. They are not thought to be caused 
by CAB, but the study staff will ask you about them. We have an information sheet about CAB and its 
side effects for you to keep. 
 
Allergic Reaction Risks – As with taking any drug, there is a risk of allergic reaction.  If you have a very 
serious allergic reaction, you may be at risk of death.  Some symptoms of allergic reactions are: 
• Rash 
• Wheezing and difficulty breathing 
• Dizziness and fainting 
• Swelling around the mouth, throat or eyes 
• A fast pulse 
• Sweating 
 
Please seek treatment immediately and tell the study doctor and study staff if you have any of these 
symptoms. 
 
Risk of HIV Resistance to CAB – We do not know if using CAB for PrEP will mean that CAB will not 
work to treat the HIV if you get infected with HIV during the study or in the future (this is called drug 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
115 of 152 
2 July 2021 
resistance). Drug resistance usually occurs when the amount of a drug in the body is too low to kill the 
virus. You will have low levels of CAB in the body for about one year after the last injection, or if you 
don’t get the injections when they are due. This is why it is very important that you use other methods to 
protect against HIV infection whenever you are at risk, like using condoms and, if you are no longer 
receiving CAB, using Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®) PrEP pills.  
 
Risks potentially related to Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®) for PrEP - Like 
all other drugs, you may have symptoms or side effects while taking PrEP. These symptoms or side 
effects may be due to participation in the study or due to illnesses that have no relation to the study, like 
a cold or flu. You should tell the study staff at the study clinic about any symptoms that you feel while 
you are participating in the study. In past PrEP research studies, nausea and diarrhea were the most 
common side effects, and happened in about 10% or 1 in 10 people. Nausea and diarrhea mainly 
happened in the first month and then went away. A small number (less than 1% or 1 out of 100 people) 
in PrEP studies showed a small decrease in how their kidneys work, but this stopped when the people 
stopped taking the study drug. Other side effects were very rare and usually resolved when the study 
drug was stopped.  
 
Risks of Asking Sensitive Questions – You may feel uncomfortable when we ask personal questions. 
You do not have to answer any question that you do not want to and you can stop answering the 
questions at any time.  
 
Risk of Disclosure of Private Information – We will make every effort to keep your information private 
and confidential. It is possible that others may learn that you are part of this study and they may think 
that you are infected with HIV or are at high risk for HIV. Because of this you may feel stigma, stress or 
embarrassment. We will not share any information about you or your health with anyone, even your 
parent/guardian, without talking to you first, except when [sites to insert relevant information about any 
legal obligations for disclosure, for example…your life is thought to be in danger]. 
 
Risks of Rectal Swabs – You may have mild discomfort when the swab is performed, particularly if you 
have hemorrhoids. In some cases, a very small amount of bleeding may occur. If you are already having 
pain in the rectal area, be sure to let the study staff know. 
 
Risks of Oral Pharyngeal Swabs – There are no risks or complications associated with this collection 
procedure. The procedure may cause momentary gagging because the back of the throat is a sensitive 
area, but it shouldn’t be painful.  
 
Other Risks – There may be uncommon or previously unknown risks that might occur. You should 
report any problems to the study staff immediately. 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
116 of 152 
2 July 2021 
 
WHAT ARE THE BENEFITS OF TAKING PART IN THIS STUDY? 
You may get direct benefit from being in this study. CAB LA has been shown to prevent HIV infections 
among adult men and transgender women. You will get information about your health and the results of 
the tests, as well as treatment for sexually transmitted infections. The counseling you get during this 
study may help you avoid HIV and other sexually transmitted infections. You or others in your 
community may benefit from this study later. The information gathered during this study may help to 
prevent the spread of HIV. This may be beneficial to you and your community.  
 
ARE THERE ANY COSTS TO ME FOR TAKING PART IN THIS STUDY? 
You will pay no money to be in the study. The study drug CAB will be provided and study procedures 
will be performed at no additional cost to you and/or your insurance company.  
 
WHAT OTHER CHOICES DO I HAVE? 
It is possible that Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®) or Tenofovir 
Alafenamide/Emtricitabine (Trade name: TAF/FTC, Descovy®) for PrEP are available in your local 
area for HIV prevention. If you prefer to take PrEP instead of joining the study, ask the study staff to 
refer you for HIV prevention medical services.  
 
[Sites to include/amend the following if applicable: There may be other studies going on here or in the 
community that you may be eligible for. If you wish, we will tell you about other studies that we know 
about. There also may be other places where you can go for HIV counseling and testing. We will tell you 
about those places if you wish.] 
 
WILL I BE TOLD IF THERE IS NEW INFORMATION? 
You will be told about any new information learned during the course of the study that might cause you 
to change your mind about being in the study. At the end of the study, you will be told when study 
results may be available and how we will let you know about the results. 
 
COMMERCIAL PROFIT 
Your biospecimens collected during this study will not be used for commercial profit. 
 
CLINICALLY RELEVANT RESULTS  
Research results that are clinically relevant, including individual research results, will be disclosed to 
you under these conditions:  
• HIV diagnostic testing results 
• Any results that affect the treatment of HIV  
 
ARE THERE ANY REASONS WHY I MAY BE ASKED TO STOP TAKING PART IN THIS 
STUDY? 
You may be withdrawn from the study if any of the following occur:  
You are unable or unwilling to attend clinic visits and/or follow all of the study procedures or 
instructions.  
You could be harmed by continuing to take the pills or getting an injection. 
The study is stopped or canceled. 
The study doctor feels that staying in the study would be harmful to you. 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
117 of 152 
2 July 2021 
Other reasons, as decided by the study staff.  
 
WHAT WILL I GET FOR TAKING PART IN THIS STUDY? 
 
You will be paid up to a total of $xx.xx if you complete this study. You will be paid for the visits you 
complete according to the following schedule: 
• $xx.xx for Visits xxx.  
• $xx.xx for Visits xxx.  
• $xx.xx for Visits xxx.  
 
If you do not complete the study, for any reason, you will be paid for each study visit you do complete.  
 
You will be paid ___________ [“after each visit,” “annually,” “bi-weekly,” etc.] 
 
If you have any questions regarding your compensation for participation, please contact the study staff.   
 
HOW WILL MY PRIVACY BE PROTECTED? 
To keep your information private, your samples will be labeled with a code that can only be traced back 
to the study clinic. Your name, where you live, and other personal information will be protected by the 
study clinic. The results of any tests done will not be included in your health records without your 
permission. Every effort will be made to keep your personal information confidential, but we cannot 
guarantee absolute confidentiality. Your records may be reviewed, under guidelines of the United States 
Federal Privacy Act, by the United States Food and Drug Administration (FDA); the sponsor of the 
study (United States National Institutes of Health [NIH]), other US, local and international regulatory 
entities may also review your study records, as well as the Advarra Institutional Review Board (IRB), 
Ethics Committees (EC), study staff, study monitors, the company that makes CAB, and other local 
authorities. Groups that oversee the study include:  
• Advarra IRB 
• [insert name of other site regulatory entities] 
• Representatives of the HPTN  
• The United States National Institutes of Health and its study monitors (including NICHD and 
its monitor, Westat) 
• The United States Food and Drug Administration 
• The United States Office for Human Research Protections 
• Other U.S., local, and international regulatory entities 
• ViiV Healthcare (the company that makes CAB) 
 
The study staff and these groups are required to keep study records private and confidential. The results 
of the study may be presented publicly or published. However, no presentation or publication will use 
your name or identify you personally. Your study information may be given to other authorities if 
required by law, including diagnoses of sexually transmitted infections. For example, we are required to 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
118 of 152 
2 July 2021 
follow state laws and report any risk of harm to you or others. This would include sexual activity with an 
adult while you are a minor. 
 
In addition to the efforts made by the study staff to help keep your personal information confidential, we 
have obtained a Certificate of Confidentiality from the U.S. Federal Government. This Certificate 
protects researchers from being forced to tell people who are not connected with this study about your 
participation. The Certificate of Confidentiality does not prevent you from releasing information about 
yourself and your participation in the study. The Certificate cannot be used to resist a demand for 
information from personnel of the United States Government that is used for auditing or evaluation of 
federally funded projects or for information that must be disclosed in order to meet the requirements of 
the federal Food and Drug Administration (FDA). Even with the Certificate of Confidentiality, if the 
study staff learns of possible child abuse and/or neglect or a risk of harm to you or others, we will tell 
the proper authorities. 
 
WHAT HAPPENS IF I AM INJURED DURING THE STUDY? 
Your health is important to us. We will make every effort to protect your well-being and minimize risks. 
It is possible, however, that you could have an illness or injury that is study-related. This means that the 
illness or injury occurred as a direct result of the study procedures or the study drug.  
 
If a study-related illness or injury occurs, we will treat you or tell you where you can get treatment. The 
cost for this treatment may be charged to you or your insurance company. There is no program for 
compensation either through the study site or the U.S. National Institutes of Health. 
 
By signing and dating this document, you will not lose any of your legal rights or release anyone 
involved in the research from responsibility for mistakes. 
 
WHOM TO CONTACT ABOUT THIS STUDY 
During the study, if you experience any medical problems, suffer a research-related injury, or have 
questions, concerns or complaints about the study, please contact the study doctor at the telephone 
number listed on the first page of this consent document. If you seek emergency care, or hospitalization 
is required, alert the treating physician that you are participating in this research study.  
 
An institutional review board (IRB) is an independent committee established to help protect the rights of 
research participants. If you have any questions about your rights as a research participant, and/or 
concerns or complaints regarding this research study, contact: 
 
• By mail: 
Study Subject Adviser 
Advarra IRB 
6940 Columbia Gateway Drive, Suite 110 
Columbia, MD 21046 
• or call toll free:    877-992-4724 
• or by email:          adviser@advarra.com 
 
Please reference the following number when contacting the Study Subject Adviser: Pro00040790. 
 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
119 of 152 
2 July 2021 
SCREENING AND ENROLLMENT CONSENT 
 
Your signature and date on this form means that: 
• You understand the information given to you in this form,  
• You accept the provisions in the form, and  
• You agree to join the study  
 
You will not give up any of your legal rights by signing and dating this consent form. 
 
I have read this form. I know that this is a research study. I have been told about the risks and potential 
benefits of taking part in the study. I have asked all the questions I have about the study and have gotten 
answers to my questions. I know that I am free to quit the study at any time without any penalties or loss 
of benefits. I will tell the study doctor or the study staff if I choose to stop the study so that I can stop in 
the best way to not harm my health. I will be given a signed and dated copy of this form to keep.  
 
I agree to take part in this research study. 
 
 
 
 
 
 
 
____________________________________ 
Participant’s Name (print) 
 
 
Signature and Date 
 
CONSENT TO TAKE PART IN THIS STUDY FOR ADOLESCENT PARTICIPANTS WHO 
HAVE REACHED THE AGE OF MAJORITY 
I have read this form. I know that this is a research study. I have been told about the risks and potential 
benefits of taking part in the study. I have asked all the questions I have about the study and have gotten 
answers to my questions. I know that I am free to quit the study at any time without any penalties or loss 
of benefits. I will tell the study doctor or the study staff if I choose to stop the study so that I can stop in 
the best way to not harm my health. I will be given a signed and dated copy of this form to keep.  
 
I agree to take part in this research study. 
 
 
 
 
 
 
 
____________________________________ 
Participant’s Name (print) 
 
 
Signature and Date 
 
 
 
 
 
 
 
 
 
 
____________________________________ 
Study Staff Conducting 
 
 
Study Staff Signature and Date 
Consent Discussion (print) 
 
 
 
 
 
 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
120 of 152 
2 July 2021 
12.9 APPENDIX IX: INFORMATION SHEET AND ASSENT FOR ADOLESCENT 
PARTICIPANTS AGES 10-13 
 
Sponsor / Study Title: 
  
Division of AIDS (DAIDS), United States (US) National 
Institute of Allergy and Infectious Diseases (NIAID), Eunice 
Kennedy Shriver National Institute of Child Health and 
Human Development (NICHD), US National Institutes of 
Health (NIH) / “HPTN 083-01: Safety, Tolerability and 
Acceptability of Long-Acting Cabotegravir (CAB LA) for 
the Prevention of HIV among Adolescent Males – A sub-
study of HPTN 083” 
 
Protocol Number: 
 
HPTN 083-01 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
 
About this research  
We are scientists doing a research study that we’d like you to join. This form explains what the study is 
about and what will happen if you decide to join. Please read it carefully. You can take as much time as 
you need to decide. Take the form home if you like. Ask the study team to explain any words or 
information that you do not understand. We will ask questions to see if we have explained the study 
clearly. After you understand the study, if you decide that you will take part, we will ask you to sign and 
date this form. You will be offered a copy to keep.  
 
Because you are still a minor, we must have permission from a parent or guardian for you to take part. 
This process is called “informed consent.” You don’t have to join the study, even if your parent or 
guardian says you should. You can also quit the study at any time, and it won’t change how you are 
treated here at the clinic.  
 
This study is about PrEP for HIV (Human Immunodeficiency Virus).  
• PrEP is short for Pre-Exposure Prophylaxis.  
• Pre-exposure means before being exposed to HIV.  
• Prophylaxis is the way people prevent a disease from infecting them. 
• With PrEP for HIV, medications are being developed to prevent people from getting HIV if they 
are exposed to it.  
• The usual PrEP medication is a pill called Truvada® that works well if taken every day. 
• Some people have a hard time remembering to take a pill every day, so it is a good idea to have 
choices. 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
121 of 152 
2 July 2021 
We’re testing a new drug called cabotegravir (CAB) to see if it can be used as PrEP to protect 
people from getting HIV. 
• CAB comes in the form of a pill and also as an injection (or ‘shot’) that’s given every 8 weeks. 
• In this study, about 50 men under 18 who do not have HIV will take CAB. We want to know: 
o Is it safe for adolescents to take CAB pills and CAB injections? 
o Is it acceptable and tolerable for adolescents to use CAB for HIV prevention? 
o Are adolescents able to make it to the clinic for injection appointments? 
o What do parents/guardians think about their sons using CAB for HIV prevention? 
• You can’t join this study if you are taking part in another study of drugs, HIV vaccines, or 
medical devices. You must tell the study staff about any other studies you are taking part in or 
thinking of taking part in. This is very important for your safety. 
 
If you join, you will complete about 18 study visits over the next 1½ years. You will move through 
the study in 3 steps: 
• Step 1: You will take one CAB pill every day for five weeks. 
• Step 2: You will receive a total of 5 CAB injections in your butt over 6 months. 
• Step 3: You will come to the clinic for study visits every 3 months for up to one year. You can 
choose either to continue CAB LA in this step, or choose to start taking the Truvada® PrEP pill 
instead. 
Different procedures are done at different study visits. The procedures include: 
• Physical examinations – We will examine you to check on your health by measuring height, 
weight, temperature and blood pressure.  
• Questions – We will ask general questions about your age, living situation, medical health, and 
as well as beliefs about HIV, opinions about taking pills and getting injections, sexual behavior, 
and any alcohol or drug use. 
• Counselling – We will discuss ways to protect you from getting HIV and offer condoms. We will 
discuss any challenges you have taking the CAB pill or attending study visits. 
• CAB pills or injection – During Step 1, we will explain how to take the study pills, watch you 
take a study pill, and explain any side effects the pills may cause. In Step 2, the CAB injection 
will be given into your butt using a needle and syringe – this will probably be painful, just like 
any other shot.  
• Laboratory tests – We will collect blood, urine, rectal swabs, and oral pharyngeal (throat) swabs 
to test for HIV, Hepatitis, liver and kidney health, cholesterol, and sexually transmitted 
infections (STIs). The needle stick can cause pain where it enters the skin and the swabs can be 
uncomfortable when they’re collected. The study staff may be required by law to report the result 
of the HIV and Hepatitis tests to the local health authority. 
• HIV Prevention – We will offer you Tenofovir/Emtricitabine (Trade name: TDF/FTC, 
Truvada®) tablets as pre-exposure prophylaxis (PrEP) after you stop the CAB injections or you 
may be able to join another CAB study.  
 
Your parent or guardian does not need to come with you to the study visits. The study visits will take 
from 1 to 4 hours each. It is important that you attend all of these study visits. If you do not come for a 
scheduled visit or if a test result comes back abnormal, study staff will contact you or visit you. We will 
ask for your address and contact information so that we will be able to get in touch with you. You 
should not join the study if it’s not okay for study staff to contact you and visit you where you stay. If at 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
122 of 152 
2 July 2021 
any time you feel sick, you should let the study staff know right away and we may ask you to come back 
for a check-up. 
 
You may benefit from taking part in this study, but there is no guarantee that it will help you. 
Being in this study may expose you to risks.   
• We may not know all the risks of CAB. 
• Some people may have bad effects or discomfort, some may be serious.  
• The most common bad effects include nausea, diarrhea, headaches and flu-like symptoms. You 
should tell the study staff whenever you don’t feel well. 
• We’ll discuss in more detail about these risks with your parent or guardian through the informed 
consent session before you decide whether you will join the study.  
• You may feel uncomfortable when we ask personal questions. You do not have to answer any 
question that you do not want to and you can stop answering the questions at any time. 
• If others find out that you are on this study, they may think you have HIV and you may feel bad.  
 
It doesn’t cost you anything to be in the study. We will cover your transport costs to come to the 
study clinic.  
 
«Compensation» 
 
You will be given $XX each time you complete a study visit. 
 
If you get HIV while you are in Step 1 of this study, you will stop using oral CAB, will exit from the 
study, and will be referred to start HIV treatment. If you get HIV while in Steps 2 or 3, you will continue 
on study with no injections and should still come for the study visits to make sure that you are doing 
okay.  
 
You might be able to get Truvada® PrEP in your local area for HIV prevention. If you prefer to take 
PrEP instead of joining the study, ask the study staff to refer you for HIV prevention medical services.  
 
We won’t tell anyone else that you are in the study.  
• We won’t share anything we find out about you with anyone, even your parent or guardian, 
without talking to you first. 
• We use a code number instead of your name on all the study forms.  
 
Have I explained the study clearly to you? Now you should ask the study staff any questions you 
have. 
 
If you have more questions later, or have any problems or complaints about the study, please 
contact the study doctor. If you are seen at another clinic for anything, let them know that you’re in 
this study and we can call them to share details.  
 
 
 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
123 of 152 
2 July 2021 
ASSENT TO TAKE PART IN THIS STUDY FOR ADOLESCENT PARTICIPANTS AGES 10-
13 
 
I have read this form. I know that this is a research study. I have been told about the risks and potential 
benefits of taking part in the study. I have asked all the questions I have about the study and have gotten 
answers to my questions. I know that I am free to quit the study at any time without any penalties or loss 
of benefits. I will tell the study doctor, the study staff or my parent(s)/guardian(s) if I choose to stop the 
study so that I can stop in the best way to not harm my health. I will be given a signed and dated copy of 
this form to keep.  
 
I agree to take part in this research study. 
 
 
 
 
 
 
 
____________________________________ 
Participant’s Name (print) 
 
 
Signature and Date 
 
 
 
 
 
 
 
____________________________________ 
Study Staff Conducting 
 
 
Study Staff Signature and Date 
Assent Discussion (print) 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
124 of 152 
2 July 2021 
12.10 APPENDIX X: INFORMED CONSENT FOR ADOLESCENT INTERVIEW FOR 
PARENTS/LEGAL GUARDIANS AND ASSENT FOR ADOLESCENT PARTICIPANTS 
AGES 14 – AGE OF MAJORITY 
 
Sponsor / Study Title: 
  
Division of AIDS (DAIDS), United States (US) National Institute 
of Allergy and Infectious Diseases (NIAID), Eunice Kennedy 
Shriver National Institute of Child Health and Human 
Development (NICHD), US National Institutes of Health (NIH) / 
“HPTN 083-01: Safety, Tolerability and Acceptability of Long-
Acting Cabotegravir (CAB LA) for the Prevention of HIV among 
Adolescent Males – A sub-study of HPTN 083” 
 
Protocol Number: 
 
HPTN 083-01 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
 
If you are a parent or legal guardian of a child participating on this study, throughout this document 
“you(r)” = “your child.” 
 
INTRODUCTION 
You are being asked to take part in an interview as part of the research study listed above. Participating 
in this interview is voluntary. You may refuse to join, or you may withdraw your consent to be 
interviewed for any reason. Before you decide whether to take part in the interview, we would like to 
explain the purpose of the interview, the risks and benefits to you and what is expected of you.  
 
This consent form gives information about taking part in the interview. We will help you to understand 
the form and answer your questions before you sign and date this form. Once you understand the details 
about taking part in the interview, and if you agree to take part, you will be asked to sign your name and 
date this form. You will be offered a copy of this form to keep. If you are a child, your parent/guardian 
must also give their permission.  
 
Participation is voluntary 
Before you learn about the interview, it is important that you know the following: 
 
Your participation is voluntary. You do not have to take part in this interview if you do not want to. You 
may decide not to take part in the interview, or you may decide to leave the interview at any time 
without losing your regular medical care. 
 
You are not required to participate in this interview in order to remain in the rest of the main study. 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
125 of 152 
2 July 2021 
About the interview 
The main study is being done to find out if it is safe and acceptable for adolescents who do not have 
HIV to take an experimental HIV drug called cabotegravir (CAB) as PrEP to prevent HIV. The 
interview portion will ask young men what they like and do not like about getting CAB injections. We 
will also ask questions to find out what makes some adolescents more or less interested in starting PrEP. 
Finally, we will ask about difficulties you had getting CAB injections and things that made that easier. 
 
Entering the interview 
In order to understand better what makes it easier or harder for young people in this study to get CAB 
injections as directed, we will be doing interviews with up to 10 young people at participating sites. You 
have been selected to take part in one interview sometime after your last Step 2 CAB injection.  
 
What will happen during the interview 
The interview will be led by a member of the research team that you do not work with during the study. 
It should take about 1 hour and your parent/guardian will not be there. [To be modified to reflect site 
practices: The interview will take place in a location that the study staff have determined will provide 
you with privacy and confidentiality such as the clinic, or another appropriate place. The study team 
will talk with you about this so you know where to go for the interview].  
 
During the interview we will ask you questions about:  
• How and when you decided to join the study 
• Whether you feel that you personally are at risk of HIV 
• How you made daily pill-taking part of your routine in Step 1 
• Where you kept your CAB pills 
• Whether you talked to your family members, peers, or partner(s) about being in this study or 
getting CAB injections in Step 2 
• If you had any bad effects from the CAB injections, and if this influenced your decision to keep 
getting the injections 
• If you are taking daily Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®) pills, how 
you feel about being on oral PrEP 
• Other related topics 
 
If any of the questions make you upset, either you or the interviewer may stop the interview at any time. 
You will also be provided with contact and referral information if any of the questions raise issues that 
you would like to talk about later. 
 
Benefits of taking part in the interview 
There may be no benefit from being interviewed. You may not receive any other direct benefit from 
being in this part of the study; however, you or others in your community may benefit from this study 
later.  
 
Risk of taking part in the interview 
There is little risk from the interview. To minimize any discomfort and to protect your privacy, the 
interview will be conducted in a private area that will allow you to speak comfortably without being 
overheard. Although we hope that you will be comfortable answering all of the questions openly and 
honestly, please keep in mind that you may refuse to answer any of the questions, or stop the interview 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
126 of 152 
2 July 2021 
completely, at any time. The greatest risk may involve your privacy and confidentiality. The steps that 
the study team have taken to protect your privacy are described below.  
 
Other information about the interview 
Privacy – Every effort will be made to keep your personal information confidential. Your personal 
information (name, address, phone number) will be protected by the research clinic. Your name, or 
anything else that might identify you personally, will not be used in any publication of information 
about this study.  
 
To help assure that we get the best understanding possible from your answers during the interview, the 
entire interview will be audio-recorded. After the interview is finished, the recording will be typed 
(called a transcript) by people who know how to do this. All identifying information will be removed 
from the transcript. Your name will not be included on the transcript. These recordings will be destroyed 
after all analysis is completed. 
 
Your records may be reviewed by the following groups, involved with the study: 
• Advarra Institutional Review Board 
• [insert name of other site regulatory entities] 
• Representatives of the HPTN  
• The United States National Institutes of Health and its study monitors (including NICHD and its 
monitor, Westat) 
• The United States Food and Drug Administration 
• The United States Office for Human Research Protections 
• Other U.S., local, and international regulatory entities 
• ViiV Healthcare (the company that makes CAB) 
 
If the study staff learns that you are at risk of harm, we will tell the proper authorities as we are required 
to do by the law. We are also required to follow state laws regarding reporting of sexual activity of 
minors with adults.  
 
New Information – You will be told any new information learned during this study that might affect 
your willingness to stay in the study. You will also be told when the results of the study may be 
available, and how to learn about them.  
 
Alternatives to participating 
You can talk to the study staff at any time about your experiences in the study, without taking part in the 
interview. 
 
There are no costs to you for being interviewed  
There will be no cost to you for participating in the in-depth interview.  
 
«Compensation» 
 
You will receive $XX for being interviewed.  You will be paid ___________ [“after each visit,” 
“annually,” “bi-weekly,” etc.] 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
127 of 152 
2 July 2021 
If you have any questions regarding your compensation for participation, please contact the study staff.   
 
Whom to contact 
If you have questions about the interview, please contact the study staff listed on page 1 of this 
document. 
 
If you have a research-related injury, please contact: [insert name of site contact] 
 
An institutional review board (IRB) is an independent committee established to help protect the rights of 
research participants. If you have any questions about your rights as a research participant, and/or 
concerns or complaints regarding this research study, contact: 
 
• By mail: 
Study Subject Adviser 
Advarra IRB 
6940 Columbia Gateway Drive, Suite 110 
Columbia, MD 21046 
• or call toll free:    877-992-4724 
• or by email:          adviser@advarra.com 
 
Please reference the following number when contacting the Study Subject Adviser: Pro00040790. 
 
 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
128 of 152 
2 July 2021 
SIGNATURE PAGE 
ADOLESCENT IN-DEPTH INTERVIEW INFORMED CONSENT FORM  
 
If you decide to join this interview portion of the main study, sign and date below. Before deciding 
whether to be interviewed, make sure you have read this form, or had it read to you, and that all of your 
questions have been answered. You should feel that you understand the study, its risks and benefits, and 
what is expected of you if you decide to join. You can ask questions or request more information at any 
time. You do not give up any rights by signing and dating this form. 
 
ADOLESCENT ASSENT FOR PARTICIPANTS AGES 14 – AGE OF MAJORITY 
 
Write your initials and sign and date below. 
 
________ 
I agree to be interviewed for the study and to have the interview audiotaped. 
 
 
________________________ 
 
____________________________________ 
Name of Participant (print) 
 
 
Signature and Date 
 
 
 
 
 
 
 
 
 
 
 
 
PARENT/GUARDIAN INFORMED CONSENT     
                           
 
________________________ 
Relationship to participant 
 
 
 
 
 
 
 
 
____________________________________ 
Name (print)  
 
 
 
Signature and Date 
 
 
 
 
 
 
 
 
____________________________________ 
Study Staff Conducting 
 
 
Study Staff Signature and Date 
Consent Discussion (print) 
 
  


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
129 of 152 
2 July 2021 
12.11 
APPENDIX XI: INFORMED CONSENT FOR ADOLESCENT INTERVIEW FOR 
ADOLESCENT PARTICIPANTS ABLE TO CONSENT FOR THEMSELVES (SELF-
CONSENT) AND PARTICIPANTS WHO REACH THE AGE OF MAJORITY  
 
Sponsor / Study Title: 
  
Division of AIDS (DAIDS), United States (US) National Institute 
of Allergy and Infectious Diseases (NIAID), Eunice Kennedy 
Shriver National Institute of Child Health and Human 
Development (NICHD), US National Institutes of Health (NIH) / 
“HPTN 083-01: Safety, Tolerability and Acceptability of Long-
Acting Cabotegravir (CAB LA) for the Prevention of HIV among 
Adolescent Males – A sub-study of HPTN 083” 
 
Protocol Number: 
 
HPTN 083-01 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
 
INTRODUCTION 
You are being asked to take part in an interview as part of the research study listed above. Participating 
in this interview is voluntary. You may refuse to join, or you may withdraw your consent to be 
interviewed for any reason. Before you decide whether to take part in the interview, we would like to 
explain the purpose of the interview, the risks and benefits to you and what is expected of you.  
 
This consent form gives information about taking part in the interview. We will help you to understand 
the form and answer your questions before you sign and date this form. Once you understand the details 
about taking part in the interview, and if you agree to take part, you will be asked to sign your name and 
date this form. You will be offered a copy of this form to keep.  
 
Participation is voluntary 
Before you learn about the interview, it is important that you know the following: 
 
Your participation is voluntary. You do not have to take part in this interview if you do not want to. You 
may decide not to take part in the interview, or you may decide to leave the interview at any time 
without losing your regular medical care. 
 
You are not required to participate in this interview in order to remain in the rest of the main study. 
 
About the interview 
The main study is being done to find out if it is safe and acceptable for adolescents who do not have 
HIV to take an experimental HIV drug called cabotegravir (CAB) as PrEP to prevent HIV. The 
interview portion will ask adolescents what they like and do not like about getting CAB injections. We 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
130 of 152 
2 July 2021 
will also ask questions to find out what makes some adolescents more or less interested in starting PrEP. 
Finally, we will ask about difficulties you had getting CAB injections and things that made that easier. 
 
Entering the interview 
In order to understand better what makes it easier or harder for young people in this study to get CAB 
injections as directed, we will be doing interviews with up to 10 young people at participating sites. You 
have been selected to take part in one interview sometime after your last Step 2 CAB injection.  
 
What will happen during the interview 
The interview will be led by a member of the research team that you do not work with during the study. 
It should take about 1 hour. [To be modified to reflect site practices: The interview will take place in a 
location that the study staff have determined will provide you with privacy and confidentiality such as 
the clinic, or another appropriate place. The study team will talk with you about this so you know where 
to go for the interview].  
 
During the interview we will ask you questions about:  
• How and when you decided to join the study 
• Whether you feel that you personally are at risk of HIV 
• How you made daily pill-taking part of your routine in Step 1 
• Where you kept your CAB pills 
• Whether you talked to your family members, peers, or partner(s) about being in this study or 
getting CAB injections in Step 2 
• If you had any bad effects from the CAB injections, and if this influenced your decision to keep 
getting the injections 
• If you are taking daily Tenofovir/Emtricitabine (Trade name: TDF/FTC, Truvada®) pills, how 
you feel about being on oral PrEP 
• Other related topics 
 
If any of the questions make you upset, either you or the interviewer may stop the interview at any time. 
You will also be provided with contact and referral information if any of the questions raise issues that 
you would like to talk about later. 
 
Benefits of taking part in the interview 
There may be no benefit from being interviewed. You may not receive any other direct benefit from 
being in this part of the study; however, you or others in your community may benefit from this study 
later.  
 
Risk of taking part in the interview 
There is little risk from the interview. To minimize any discomfort and to protect your privacy, the 
interview will be conducted in a private area that will allow you to speak comfortably without being 
overheard. Although we hope that you will be comfortable answering all of the questions openly and 
honestly, please keep in mind that you may refuse to answer any of the questions, or stop the interview 
completely, at any time. The greatest risk may involve your privacy and confidentiality. The steps that 
the study team have taken to protect your privacy are described below.  
 
Other information about the interview 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
131 of 152 
2 July 2021 
Privacy – Every effort will be made to keep your personal information confidential. Your personal 
information (name, address, phone number) will be protected by the research clinic. Your name, or 
anything else that might identify you personally, will not be used in any publication of information 
about this study.  
 
To help assure that we get the best understanding possible from your answers during the interview, the 
entire interview will be audio-recorded. After the interview is finished, the recording will be typed 
(called a transcript) by people who know how to do this. All identifying information will be removed 
from the transcript. Your name will not be included on the transcript. These recordings will be destroyed 
after all analysis is completed. 
 
Your records may be reviewed by the following groups, involved with the study: 
• Advarra Institutional Review Board 
• [insert name of other site regulatory entities] 
• Representatives of the HPTN  
• The United States National Institutes of Health and its study monitors (including NICHD and its 
monitor, Westat) 
• The United States Food and Drug Administration 
• The United States Office for Human Research Protections 
• Other U.S., local, and international regulatory entities 
• ViiV Healthcare (the company that makes CAB) 
 
If the study staff learns that you are at risk of harm, we will tell the proper authorities as we are required 
to do by the law. We are also required to follow state laws regarding reporting of sexual activity of 
minors with adults.  
 
New Information – You will be told any new information learned during this study that might affect 
your willingness to stay in the study. You will also be told when the results of the study may be 
available, and how to learn about them.  
 
Alternatives to participating 
You can talk to the study staff at any time about your experiences in the study, without taking part in the 
interview. 
 
There are no costs to you for being interviewed  
There will be no cost to you for participating in the in-depth interview.  
 
«Compensation» 
 
You will receive $XX for being interviewed.  You will be paid ___________ [“after each visit,” 
“annually,” “bi-weekly,” etc.] 
 
If you have any questions regarding your compensation for participation, please contact the study staff.   
 
Whom to contact 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
132 of 152 
2 July 2021 
If you have questions about the interview, please contact the study staff listed on page 1 of this 
document. 
 
If you have a research-related injury, please contact: [insert name of site contact] 
 
An institutional review board (IRB) is an independent committee established to help protect the rights of 
research participants. If you have any questions about your rights as a research participant, and/or 
concerns or complaints regarding this research study, contact: 
 
• By mail: 
Study Subject Adviser 
Advarra IRB 
6940 Columbia Gateway Drive, Suite 110 
Columbia, MD 21046 
• or call toll free:    877-992-4724 
• or by email:          adviser@advarra.com 
 
Please reference the following number when contacting the Study Subject Adviser: Pro00040790. 
 
 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
133 of 152 
2 July 2021 
SIGNATURE PAGE 
 
ADOLESCENT SELF-CONSENT FOR IN-DEPTH INTERVIEW  
 
If you decide to join this interview portion of the main study, sign and date below. Before deciding 
whether to be interviewed, make sure you have read this form, or had it read to you, and that all of your 
questions have been answered. You should feel that you understand the study, its risks and benefits, and 
what is expected of you if you decide to join. You can ask questions or request more information at any 
time. You do not give up any rights by signing and dating this form. 
 
Write your initials and sign and date below. 
 
________ 
I agree to be interviewed for the study and to have the interview audiotaped. 
 
 
________________________ 
 
____________________________________ 
Name of Participant (print) 
 
 
Signature and Date 
 
 
CONSENT FOR PARTICIPANTS WHO REACH THE AGE OF MAJORITY 
 
Write your initials and sign and date below. 
 
________ 
I agree to be interviewed for the study and to have the interview audiotaped. 
 
 
________________________ 
 
____________________________________ 
Name of Participant (print) 
 
 
Signature and Date 
 
 
 
 
 
 
 
 
____________________________________ 
Study Staff Conducting 
 
 
Study Staff Signature and Date 
Consent Discussion (print) 
 
 
 
 
 
 
 
 
 
 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
134 of 152 
2 July 2021 
12.12 
  APPENDIX XII: INFORMATION SHEET AND ASSENT FOR ADOLESCENT 
INTERVIEWS FOR PARTICIPANTS AGES 10-13 
 
Sponsor / Study Title: 
  
Division of AIDS (DAIDS), United States (US) National 
Institute of Allergy and Infectious Diseases (NIAID), Eunice 
Kennedy Shriver National Institute of Child Health and 
Human Development (NICHD), US National Institutes of 
Health (NIH) / “HPTN 083-01: Safety, Tolerability and 
Acceptability of Long-Acting Cabotegravir (CAB LA) for 
the Prevention of HIV among Adolescent Males – A sub-
study of HPTN 083” 
 
Protocol Number: 
 
HPTN 083-01 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
 
About this form 
You have decided to join the study named above, with permission from your parent or guardian. We 
also invite you to be interviewed for this study. This interview part will ask young people what they like 
and do not like about getting CAB injections. We will also ask questions to find out what makes some 
young people more or less interested in starting PrEP. Finally, we will ask about difficulties you had 
getting CAB injections and things that made that easier. Joining this interview part is voluntary.  
• You can take as much time as you need to decide. Take the form home if you like.  
• Ask the study team to explain any words or information that you do not understand. We will ask 
questions to see if we have explained it clearly.  
• After you understand the interview part, we will ask you to sign and date this form.  
• You will be offered a signed and dated copy to keep. 
• It is your decision whether or not to be interviewed. You are free to say yes or no, and to change 
your mind at any time.  
• If you say no, you can still be in the main study.  
 
What will happen if you agree to be interviewed 
One of the study staff that you do not work with during the study will interview you at [Site to insert 
location]. It will be for about 1 hour. Your parent or guardian will not be there. We will ask you 
questions about joining the main study and who you talked to about the study. We will also ask about 
your experiences with taking the study pills and having the injections. We will ask what you feel about 
your risk of getting HIV and such topics. 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
135 of 152 
2 July 2021 
If any of the questions make you upset, either you or the interviewer may stop the interview at any time. 
You will also be provided with contact and referral information if any of the questions raise issues that 
you would like to talk about later. 
 
A code number will be used instead of your name on all the study forms and information gathered 
during the interview will not be shared with your parents or guardian(s) without your permission. 
 
Being interviewed won’t benefit you in any way, but the information we get from the interviews may 
benefit your community later.  
 
«Compensation» 
 
You will be given $XX for the cost of transport to the clinic for the interview.  
 
Have I explained the interview part of this study clearly to you? Now you should ask the study 
staff any questions you have. 
 
If you have more questions later, or have any problems or complaints about the study, please 
contact the study doctor. If you are seen at another clinic for anything, let them know that you’re in 
this study and we can call them to share details.  
 
ASSENT TO TAKE PART IN THIS STUDY FOR ADOLESCENT PARTICIPANTS AGES 10-
13 
I agree to be interviewed for the study and to have the interview audiotaped. 
 
 
 
 
 
 
 
____________________________________ 
Participant’s Name (print) 
 
 
Signature and Date 
 
 
 
 
 
 
 
____________________________________ 
Study Staff Conducting 
 
 
Study Staff Signature and Date 
Assent Discussion (print) 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
136 of 152 
2 July 2021 
12.13 
APPENDIX XIII: INFORMED CONSENT PARENT/GUARDIAN INTERVIEW 
FOR PARENTS/LEGAL GUARDIANS 
 
Sponsor / Study Title: 
  
Division of AIDS (DAIDS), United States (US) National 
Institute of Allergy and Infectious Diseases (NIAID), Eunice 
Kennedy Shriver National Institute of Child Health and 
Human Development (NICHD), US National Institutes of 
Health (NIH) / “HPTN 083-01: Safety, Tolerability and 
Acceptability of Long-Acting Cabotegravir (CAB LA) for 
the Prevention of HIV among Adolescent Males – A sub-
study of HPTN 083” 
 
Protocol Number: 
 
HPTN 083-01 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
 
INTRODUCTION 
You are being asked to take part in an interview for the research study listed above. Joining this 
interview is voluntary. You may refuse to join, or you may withdraw your consent to be interviewed for 
any reason. Before you decide whether to join the interview, we would like to explain the purpose of the 
interview, the risks and benefits to you and what is expected of you.  
 
This consent form gives information about being in the interview. We will help you to understand the 
form and answer your questions before you sign and date this form. Once you understand the interview, 
and if you agree to take part, you will be asked to sign your name and date this form. You will be 
offered a copy of this form to keep.  
 
Participation is voluntary 
Before you learn about the interview, it is important that you know the following: 
 
Your participation is voluntary. You do not have to take part in the interview if you do not want to. You 
may decide not to take part in the interview, or you may decide to leave the interview at any time 
without losing your regular medical care. 
 
You are not required to participate in these interviews in order for your child to remain in the rest of the 
study. 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
137 of 152 
2 July 2021 
About the interview 
The main study is being done to find out if it is safe and acceptable for adolescents who do not have 
HIV to take an experimental HIV drug called cabotegravir (CAB) as PrEP to prevent HIV. This 
interview will ask parents/guardians questions to find out what it is like to have a child getting CAB 
injections and things that made that easier. We will also ask young people what they like and do not like 
about getting CAB injections.  
 
Entering the interview 
We will be doing interviews with up to 10 parents/guardians at participating sites (total, across sites). 
You have been selected to take part in one interview sometime after your child’s last Step 2 CAB 
injection.  
 
What will happen during the interview 
The interview will be led by a member of the research team that you do not work with during the study. 
It should take about 1 hour and your child will not be there. [To be modified to reflect site practices: The 
interview will take place in a location that the study staff have determined will provide you with privacy 
and confidentiality such as the clinic, or another appropriate place. The study team will talk with you 
about this so you know where to go for the interview].  
 
During the interview we will ask you questions about:  
• How and when you decided to allow your child to join the study 
• Whether you feel that they personally are at risk of HIV 
• Whether you talked to your children about sexual activity or preventing HIV 
• If your child had any bad effects from being in the study, and if this influenced your decision to 
keep coming for the study visits 
• Other related topics 
 
If any of the questions make you upset, either you or the interviewer may stop the interview at any time. 
You will also be provided with contact and referral information if any of the questions raise issues that 
you would like to talk about later. 
 
Benefits of the interview 
There may be no benefit from being interviewed. You may not receive any other direct benefit from 
being in this part of the study; however, you or others in your community may benefit from this study 
later.  
 
Risk of the interview 
There is little risk from the interview. To minimize any discomfort and to protect your privacy, the 
interview will be conducted in a private area that will allow you to speak comfortably without being 
overheard. Although we hope that you will be comfortable answering all of the questions openly and 
honestly, please keep in mind that you may refuse to answer any of the questions, or stop the interview 
completely, at any time. The greatest risk may involve your privacy and confidentiality. The steps that 
the study team have taken to protect your privacy are described below.  
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
138 of 152 
2 July 2021 
Other information about the interview 
Privacy – Every effort will be made to keep your personal information confidential. Your personal 
information (name, address, phone number) will be protected by the research clinic. Your name, or 
anything else that might identify you personally, will not be used in any publication of information 
about this study.  
 
To help assure that we get the best understanding possible from your answers during the interview, the 
entire interview will be audio-recorded. After the interview is finished, the recording will be typed 
(called a transcript) by people who know how to do this. All identifying information will be removed 
from the transcript. Your name will not be included on the transcript. These recordings will be destroyed 
after all analysis is completed. 
 
Your records may be reviewed by the following groups, involved with the study: 
• Advarra Institutional Review Board 
• [insert name of other site regulatory entities] 
• Representatives of the HPTN  
• The United States National Institutes of Health and its study monitors (including NICHD and its 
monitor, Westat) 
• The United States Food and Drug Administration 
• The United States Office for Human Research Protections 
• Other U.S., local, and international regulatory entities 
• ViiV Healthcare (the company that makes CAB) 
 
If the study staff learns that you are at risk of harm, we will tell the proper authorities as we are required 
to do by the law. 
 
New Information – You will be told any new information learned during this study that might affect 
your willingness to stay in the study. You will also be told when the results of the study may be 
available, and how to learn about them.  
 
Alternatives to participating 
You can talk to the study staff at any time about your child’s experiences in the study, without taking 
part in the interview. 
 
There are no costs to you for being interviewed 
There will be no cost to you for participating in the in-depth interview.  
 
«Compensation» 
 
You will receive $XX for being interviewed. You will be paid ___________ [“after each visit,” 
“annually,” “bi-weekly,” etc.] 
 
If you have any questions regarding your compensation for participation, please contact the study staff.   
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
139 of 152 
2 July 2021 
Whom to contact 
If you have questions about the interview, please contact the study staff listed on page 1 of this 
document. 
 
If you have a research-related injury, please contact: [insert name of site contact] 
 
An institutional review board (IRB) is an independent committee established to help protect the rights of 
research participants. If you have any questions about your rights as a research participant, and/or 
concerns or complaints regarding this research study, contact: 
 
• By mail: 
Study Subject Adviser 
Advarra IRB 
6940 Columbia Gateway Drive, Suite 110 
Columbia, MD 21046 
• or call toll free:    877-992-4724 
• or by email:          adviser@advarra.com 
 
Please reference the following number when contacting the Study Subject Adviser: Pro00040790. 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
140 of 152 
2 July 2021 
SIGNATURE PAGE 
PARENT/GUARDIAN IN-DEPTH INTERVIEW INFORMED CONSENT FORM  
 
If you decide to be interviewed, sign and date below. Before deciding whether to join this study, make 
sure you have read this form and that all of your questions have been answered. You should feel that you 
understand the study, its risks and benefits, and what is expected of you if you decide to join. You can 
ask questions or request more information at any time. You do not give up any rights by signing and 
dating this form. 
 
 
 
__________________________ 
 
___________________________________ 
Name of Parent/Guardian (print) 
 
Signature and Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
__________________________ 
 
___________________________________ 
Study Staff Conducting 
 
 
Study Staff Signature and Date 
Consent Discussion (print) 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
141 of 152 
2 July 2021 
12.14 
APPENDIX XIV: INFORMED CONSENT FOR SPECIMEN STORAGE AND 
FUTURE USE FOR PARENTS/LEGAL GUARDIANS AND ASSENT FOR ADOLESCENT 
PARTICIPANTS AGES 14 – AGE OF MAJORITY 
 
Sponsor / Study Title: 
  
Division of AIDS (DAIDS), United States (US) National Institute 
of Allergy and Infectious Diseases (NIAID), Eunice Kennedy 
Shriver National Institute of Child Health and Human 
Development (NICHD), US National Institutes of Health (NIH) / 
“HPTN 083-01: Safety, Tolerability and Acceptability of Long-
Acting Cabotegravir (CAB LA) for the Prevention of HIV among 
Adolescent Males – A sub-study of HPTN 083” 
 
Protocol Number: 
 
HPTN 083-01 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
 
If you are a parent or legal guardian of a child participating on this study, throughout this document 
“you(r)” = “your child.” 
 
INTRODUCTION 
You have decided to join the study named above. As part of the study, you will have blood, urine, rectal 
swab, and oral pharyngeal swabs collected. After all the tests for this study have been done, there may 
be some samples left over. We call these left over samples. The study doctor would like to keep these 
left over samples and use them for other research in the future. This form gives information about use of 
left over samples. Please read it and ask any questions you may have. After we discuss the information 
with you, you will record your decisions on use of extra samples at the end of the form.  
 
1. It is your decision whether or not to allow the left over samples to be used.  
You are free to say yes or no, and to change your mind at any time. Your decision will not affect your 
participation in the study. If you say no, all left over samples will be destroyed.  
 
2. If you agree, your left over samples will be kept in a repository.  
A repository is a secure facility that is used to store samples. The HPTN repository is in the United 
States. If you agree to have left over samples stored, the samples will be kept in this repository. There is 
no limit on how long the samples will be kept. 
 
3. Left over samples could be used for different types of research.  
Left over samples may be used for research on HIV and other infections, including testing for the 
medicines used in this study and other anti-HIV medicines, the immune system, and other diseases. The 
research may be done in the United States or in other locations. If you agree, the leftover samples could 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
142 of 152 
2 July 2021 
also be used for research that looks at your genes. Genes are passed to children from their birth parents. 
They affect how people look and how their bodies work. Differences in people’s genes can help explain 
why some people get a disease while others do not. Your samples would only be used to look at genes 
related to how the body responds to the study drugs and the immune system. These tests would not 
include whole genome sequencing (WGS). 
 
Any research done with the leftover samples must be reviewed and approved by the HPTN. The 
research must also be approved by an ethics committee. The role of an ethics committee is to review the 
research plan and protect the rights and well-being of the people whose samples will be used.  
 
The research done with left over samples is not expected to give any information relevant to your health. 
Therefore, the results will not be given to the study staff or to you. The results also will not be placed in 
your study records. 
 
4. There is little risk to you.  
When left over samples are used for research, they are labeled with a code number only. To protect your 
privacy, no names are used. However, information such as age, gender, HIV status, and other health 
information may be linked to the samples. There may be some risks from tests of your genes. If others 
found out the results of these tests, they could treat you badly or unfairly. However, this is almost 
impossible because the results will not be given to the study staff or to you and will not be in his study 
records.  
 
Any identifiers will be removed from the identifiable private information or biospecimens and, after 
removal, the information or biospecimens can be used for future research studies or distributed to 
another investigator for future research studies without additional informed consent. 
 
5. There may be no benefit to you.  
You will not get direct benefit from storage of the samples. You or others in your community may 
benefit from this study later. The information gathered during this study may help to prevent the spread 
of HIV. This may be beneficial to you and your community.   
 
6. You will not be paid for use of your samples. 
There is no cost to you for use of your leftover samples. The samples will not be sold, and you will not 
be paid for use of the samples. It is possible that research done with the samples could lead to a new 
discovery or a new product. If this happens, there is no plan to share any money with you.  
 
7. Information from research using extra samples may be reviewed by groups that oversee the 
research. 
These groups include:   
• Advarra Institutional Review Board 
• [insert name of other site regulatory entities] 
• Representatives of the HPTN  
• The United States National Institutes of Health and its study monitors (including NICHD and its 
monitor, Westat) 
• The United States Food and Drug Administration 
• The United States Office for Human Research Protections 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
143 of 152 
2 July 2021 
• Other U.S., local, and international regulatory entities 
• ViiV Healthcare (the company that makes CAB) 
 
The people who do research with the leftover samples and the groups listed above are required to make 
efforts to keep information private and confidential. 
 
The results of research done with the leftover samples may be presented publicly or published. 
However, no presentation or publication will use your name or identify you personally.  
 
8. Whom to contact about this sub-study 
During the study, if you experience any medical problems, suffer a research-related injury, or have 
questions, concerns or complaints about the study, please contact the study doctor at the telephone 
number listed on the first page of this consent document. If you seek emergency care, or hospitalization 
is required, alert the treating physician that you are participating in this research study.  
 
An institutional review board (IRB) is an independent committee established to help protect the rights of 
research participants. If you have any questions about your rights as a research participant, and/or 
concerns or complaints regarding this research study, contact: 
 
• By mail: 
Study Subject Adviser 
Advarra IRB 
6940 Columbia Gateway Drive, Suite 110 
Columbia, MD 21046 
• or call toll free:    877-992-4724 
• or by email:          adviser@advarra.com 
 
Please reference the following number when contacting the Study Subject Adviser: Pro00040790. 
 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
144 of 152 
2 July 2021 
SPECIMEN STORAGE AND FUTURE USE INFORMED CONSENT 
 
Before deciding about storage of laboratory specimens, make sure you have read this form and that all of 
your questions have been answered.  You should feel that you understand your options and the possible 
risks and benefits before making your decision. You and your child do not give up any rights by signing 
and dating this form. 
 
For your child’s leftover samples, write your initials next to your choice (choose only one). 
 
__________ I allow my child’s leftover samples to be used for research on HIV and other infections, 
including testing for the study drugs and other anti-HIV medicines, the immune system, and other 
diseases. I also allow my child’s samples to be used for tests of his genes.  
 
__________ I allow my child’s leftover samples to be used for research on HIV and other infections, 
including testing for the study drugs and other anti-HIV medicines, the immune system, and other 
diseases. I do not allow my child’s samples to be used for tests of his genes.  
 
__________ I do not allow my child’s leftover samples to be used for any research. 
 
 
 
 
 
 
 
 
Participant’s Name (print) 
 
 
 
 
PARENT/GUARDIAN INFORMED CONSENT                               
 
________________________ 
Relationship to participant 
 
 
 
 
 
 
 
____________________________________ 
Name (print)  
 
 
 
Signature and Date 
 
ASSENT FOR ADOLESCENT PARTICIPANTS AGES 14 YEARS – AGE OF MAJORITY 
I have read this form. I have asked all the questions I have about the study and have gotten answers to 
my questions. I will be given a signed and dated copy of this form to keep.  
 
For your leftover samples, write your initials next to your choice (choose only one). 
 
__________ I allow my leftover samples to be used for research on HIV and other infections, 
including testing for the study drugs and other anti-HIV medicines, the immune system, and other 
diseases. I also allow my samples to be used for tests of my genes.  
 
__________ I allow my leftover samples to be used for research on HIV and other infections, 
including testing for the study drugs and other anti-HIV medicines, the immune system, and other 
diseases. I do not allow my samples to be used for tests of my genes.  
 
__________ I do not allow my leftover samples to be used for any research. 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
145 of 152 
2 July 2021 
 
 
 
 
 
 
____________________________________ 
Participant’s Name (print) 
 
 
Signature and Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
146 of 152 
2 July 2021 
12.15 
APPENDIX XV: INFORMED CONSENT FOR SPECIMEN STORAGE AND 
FUTURE USE FOR ADOLESCENT PARTICIPANTS ABLE TO CONSENT FOR 
THEMSELVES (SELF-CONSENT) AND PARTICIPANTS WHO REACH THE AGE OF 
MAJORITY 
 
Sponsor / Study Title: 
  
Division of AIDS (DAIDS), United States (US) National Institute 
of Allergy and Infectious Diseases (NIAID), Eunice Kennedy 
Shriver National Institute of Child Health and Human 
Development (NICHD), US National Institutes of Health (NIH) / 
“HPTN 083-01: Safety, Tolerability and Acceptability of Long-
Acting Cabotegravir (CAB LA) for the Prevention of HIV among 
Adolescent Males – A sub-study of HPTN 083” 
 
Protocol Number: 
 
HPTN 083-01 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
 
 
INTRODUCTION 
You have decided to join the study named above. As part of the study, you will have blood, urine, rectal 
swab, and oral pharyngeal swabs collected. After all the tests for this study have been done, there may 
be some samples left over. We call these left over samples. The study doctor would like to keep these 
left over samples and use them for other research in the future. This form gives information about use of 
left over samples. Please read it and ask any questions you may have. After we discuss the information 
with you, you will record your decisions on use of extra samples at the end of the form.  
 
1. It is your decision whether or not to allow the left over samples to be used.  
You are free to say yes or no, and to change your mind at any time. Your decision will not affect your 
participation in the study. If you say no, all left over samples will be destroyed.  
 
2. If you agree, your left over samples will be kept in a repository.  
A repository is a secure facility that is used to store samples. The HPTN repository is in the United 
States. If you agree to have left over samples stored, the samples will be kept in this repository. There is 
no limit on how long the samples will be kept. 
 
3. Left over samples could be used for different types of research.  
Left over samples may be used for research on HIV and other infections, including testing for the 
medicines used in this study and other anti-HIV medicines, the immune system, and other diseases. The 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
147 of 152 
2 July 2021 
research may be done in the United States or in other locations. If you agree, the leftover samples could 
also be used for research that looks at your genes. Genes are passed to children from their birth parents. 
They affect how people look and how their bodies work. Differences in people’s genes can help explain 
why some people get a disease while others do not. Your samples would only be used to look at genes 
related to how the body responds to the study drugs and the immune system. These tests would not 
include whole genome sequencing (WGS). 
 
Any research done with the leftover samples must be reviewed and approved by the HPTN. The 
research must also be approved by an ethics committee. The role of an ethics committee is to review the 
research plan and protect the rights and well-being of the people whose samples will be used.  
 
The research done with left over samples is not expected to give any information relevant to your health. 
Therefore, the results will not be given to the study staff or to you. The results also will not be placed in 
your study records. 
 
4. There is little risk to you.  
When left over samples are used for research, they are labeled with a code number only. To protect your 
privacy, no names are used. However, information such as age, gender, HIV status, and other health 
information may be linked to the samples. There may be some risks from tests of your genes. If others 
found out the results of these tests, they could treat you badly or unfairly. However, this is almost 
impossible because the results will not be given to the study staff or to you and will not be in your study 
records.  
 
Any identifiers will be removed from the identifiable private information or biospecimens and, after 
removal, the information or biospecimens can be used for future research studies or distributed to 
another investigator for future research studies without additional informed consent. 
 
5. There may be no benefit to you.  
You will not get direct benefit from storage of the samples. You or others in your community may 
benefit from this study later. The information gathered during this study may help to prevent the spread 
of HIV. This may be beneficial to you and your community.   
 
6. You will not be paid for use of your samples. 
There is no cost to you for use of your leftover samples. The samples will not be sold, and you will not 
be paid for use of the samples. It is possible that research done with the samples could lead to a new 
discovery or a new product. If this happens, there is no plan to share any money with you.  
 
7. Information from research using extra samples may be reviewed by groups that oversee the 
research. 
These groups include:   
• Advarra Institutional Review Board 
• [insert name of other site regulatory entities] 
• Representatives of the HPTN  


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
148 of 152 
2 July 2021 
• The United States National Institutes of Health and its study monitors (including NICHD and its 
monitor, Westat) 
• The United States Food and Drug Administration 
• The United States Office for Human Research Protections 
• Other U.S., local, and international regulatory entities 
• ViiV Healthcare (the company that makes CAB) 
 
The people who do research with the leftover samples and the groups listed above are required to make 
efforts to keep information private and confidential. 
 
The results of research done with the leftover samples may be presented publicly or published. 
However, no presentation or publication will use your name or identify you personally.  
 
8. Whom to contact about this sub-study 
During the study, if you experience any medical problems, suffer a research-related injury, or have 
questions, concerns or complaints about the study, please contact the study doctor at the telephone 
number listed on the first page of this consent document. If you seek emergency care, or hospitalization 
is required, alert the treating physician that you are participating in this research study.  
 
An institutional review board (IRB) is an independent committee established to help protect the rights of 
research participants. If you have any questions about your rights as a research participant, and/or 
concerns or complaints regarding this research study, contact: 
 
• By mail: 
Study Subject Adviser 
Advarra IRB 
6940 Columbia Gateway Drive, Suite 110 
Columbia, MD 21046 
• or call toll free:    877-992-4724 
• or by email:          adviser@advarra.com  
 
Please reference the following number when contacting the Study Subject Adviser: Pro00040790. 
 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
149 of 152 
2 July 2021 
SPECIMEN STORAGE AND FUTURE USE INFORMED CONSENT (SELF-CONSENT) 
 
Before deciding about storage of laboratory specimens, make sure you have read this form and that all of 
your questions have been answered.  You should feel that you understand your options and the possible 
risks and benefits before making your decision. You do not give up any rights by signing and dating this 
form. 
 
For your leftover samples, write your initials next to your choice (choose only one). 
 
__________ I allow my leftover samples to be used for research on HIV and other infections, 
including testing for the study drugs and other anti-HIV medicines, the immune system, and other 
diseases. I also allow my samples to be used for tests of my genes.  
 
__________ I allow my leftover samples to be used for research on HIV and other infections, 
including testing for the study drugs and other anti-HIV medicines, the immune system, and other 
diseases. I do not allow my samples to be used for tests of my genes.  
 
__________ I do not allow my leftover samples to be used for any research. 
 
 
 
 
 
 
 
____________________________________ 
Participant’s Name (print) 
 
 
 
 
Signature and Date 
 
 
 
 
 
 
 
____________________________________ 
Study Staff Conducting 
 
 
Study Staff Signature and Date 
Consent Discussion (print) 
 
 
CONSENT FOR ADOLESCENT PARTICIPANTS WHO REACH THE AGE OF MAJORITY 
I have read this form. I have asked all the questions I have about the study and have gotten answers to 
my questions. I will be given a signed and dated copy of this form to keep.  
 
For your leftover samples, write your initials next to your choice (choose only one). 
 
__________ I allow my leftover samples to be used for research on HIV and other infections, 
including testing for the study drugs and other anti-HIV medicines, the immune system, and other 
diseases. I also allow my samples to be used for tests of my genes.  
 
__________ I allow my leftover samples to be used for research on HIV and other infections, 
including testing for the study drugs and other anti-HIV medicines, the immune system, and other 
diseases. I do not allow my samples to be used for tests of my genes.  
 
__________ I do not allow my leftover samples to be used for any research. 
 
 
 
 
 
 
 
____________________________________ 
Participant’s Name (print) 
 
 
Signature and Date 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
150 of 152 
2 July 2021 
 
 
 
 
 
 
 
____________________________________ 
Study Staff Conducting 
 
 
Study Staff Signature and Date 
Consent Discussion (print) 
 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
151 of 152 
2 July 2021 
12.16 
APPENDIX XVI: INFORMATION SHEET AND ASSENT FOR SPECIMEN 
STORAGE AND FUTURE USE FOR PARTICIPANTS AGES 10-13 
 
Sponsor / Study Title: 
  
Division of AIDS (DAIDS), United States (US) National Institute 
of Allergy and Infectious Diseases (NIAID), Eunice Kennedy 
Shriver National Institute of Child Health and Human 
Development (NICHD), US National Institutes of Health (NIH) / 
“HPTN 083-01: Safety, Tolerability and Acceptability of Long-
Acting Cabotegravir (CAB LA) for the Prevention of HIV among 
Adolescent Males – A sub-study of HPTN 083” 
 
Protocol Number: 
 
HPTN 083-01 
Principal Investigator: 
(Study Doctor) 
 
«PiFullName» 
 
Telephone: 
 
«IcfPhoneNumber» 
 
Address: 
«PiLocations» 
 
 
About this form 
You have decided to join the study named above, with permission from your parent or guardian. As part 
of the study, we will collect lab samples for the study tests. After all the tests for this study have been 
done, there may be some of the samples left over. We call these leftover samples. The study doctor 
would like to keep these leftover samples and use them for other research in the future, if you and your 
parent or guardian agree. 
• You can take as much time as you need to decide. Take the form home if you like.  
• Ask the study team to explain any words or information that you do not understand. We will ask 
questions to see if we have explained it clearly.  
• After you understand specimen storage, we will ask you to enter your decision and then sign and 
date this form.  
• You will be offered a signed and dated copy to keep. 
• It is your decision whether or not to allow the leftover samples to be used. You are free to say 
yes or no, and to change your mind at any time.  
• If you say no, you can still join the main study and all your leftover samples will be destroyed at 
the end.  
 
What will happen if you agree to store your leftover samples 
If you agree, your leftover samples will be kept in a secure storage lab called a repository in [Sites 
should insert the location]. There is no limit on how long the samples will be kept. Leftover samples 
could be used for different types of research, mostly related to HIV, testing for anti-HIV medicines, the 
immune system, and other diseases. If you agree, the leftover samples could also be used for research 
that looks at your genes, but these tests would not include whole genome sequencing (WGS). 
 


Division of AIDS (DAIDS), United States (US) National Institute of Allergy and Infectious Diseases (NIAID), Eunice Kennedy Shriver National 
Institute of Child Health and Human Development (NICHD), US National Institutes of Health (NIH) / Protocol Number HPTN 083-01 
 
HPTN 083-01, FINAL V3.0 
152 of 152 
2 July 2021 
This research may be done in the United States or other countries. Any research done with the leftover 
samples must be reviewed and approved by the HPTN and an ethics committee to protect your rights 
and well-being. We won’t give you the results of any tests done on your leftover samples because they 
won’t be relevant to your health. Leftover samples are labeled with a code number only, not your name. 
Only your age, gender, HIV status, and other health information may be linked to the samples.  
 
Storing your samples won’t benefit you in any way, but the information we get from these future studies 
may benefit your community later. The samples will not be sold, and you will not be paid for use of the 
samples.  
 
Have I explained the specimen storage clearly to you? Now you should ask the study staff any 
questions you have. 
 
If you have more questions later, or have any problems or complaints about the study, please 
contact the study doctor. If you are seen at another clinic for anything, let them know that you’re in 
this study and we can call them to share details.  
 
ASSENT TO TAKE PART IN THIS STUDY FOR ADOLESCENT PARTICIPANTS AGES 10-
13 
For your leftover samples, write your initials next to your choice (choose only one). 
 
__________ I allow my leftover samples to be used for research on HIV and other infections, 
including testing for the study drugs and other anti-HIV medicines, the immune system, and other 
diseases. I also allow my samples to be used for tests of my genes.  
 
__________ I allow my leftover samples to be used for research on HIV and other infections, 
including testing for the study drugs and other anti-HIV medicines, the immune system, and other 
diseases. I do not allow my samples to be used for tests of my genes.  
 
__________ I do not allow my leftover samples to be used for any research. 
 
 
 
 
 
 
 
____________________________________ 
Participant’s Name (print) 
 
 
Signature and Date 
 
 
 
 
 
 
 
____________________________________ 
Study Staff Conducting 
 
 
Study Staff Signature and Date 
Assent Discussion (print) 
 
 
 
 
 
                                                                                                                                                                         
 

SAP_002.pdf: 
 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 1 of 27 
 
 
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN  
 
 
Safety, Tolerability and Acceptability of Long-Acting 
Cabotegravir (CAB LA) for the Prevention of HIV among 
Adolescent Males – A Sub-study of HPTN 083 
 
HPTN 083-01 
 
 Effective Date: [Date of latest signature] 
Version: [2.0] 
 
 
 
 
 
 
 
 
 
 
 
 
 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 2 of 27 
 
 
STATISTICAL ANALYSIS PLAN 
 
Protocol Name:  
Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB 
LA) for the Prevention of HIV among Adolescent Males– A Sub-study of 
HPTN 083 
Protocol Number:  
 
HPTN 083-01 
Author(s):  
Brett Hanscom, Timothy Skalland, Xu (Amber) Guo, Yuqing Jiao 
Version:  
2.0 
 
Author(s): 
 
 
Brett Hanscom 
 
 
 
See eTMF Signature 
Manifest 
 
 
See eTMF Signature 
Manifest 
Lead Statistician 
 
 
Xu (Amber) Guo 
 
 
Signature 
 
See eTMF Signature 
Manifest  
 
Date: DD/MM/YYYY 
 
See eTMF Signature 
Manifest 
Statistical Research Associate 
 
 
 
 
Signature 
 
Date: DD/MM/YYYY 
Approvals:  
 
 
 
 
 
 
 
 
 
NIAID Statistical Reviewer 
 
 
Signature  
 
Date: DD/MM/YYYY 
 
 
 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024
Zonghui 
Hu -S
Digitally signed by 
Zonghui Hu -S 
Date: 2023.01.06 
16:44:38 -05'00'


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 3 of 27 
 
 
TABLE OF CONTENTS 
1. 
LIST OF ABBREVIATIONS AND ACRONYMS .................................................................... 5 
2. 
INTRODUCTION ............................................................................................................ 7 
2.1 
GENERAL DESIGN CONSIDERATIONS ........................................................................................... 7 
2.2 
STUDY OBJECTIVES AND ENDPOINTS ........................................................................................... 8 
2.3 
RANDOMIZATION .................................................................................................................... 9 
2.4 
BLINDING .............................................................................................................................. 9 
2.5 
SAMPLE SIZE AND POWER ........................................................................................................ 9 
3. 
GENERAL DATA ANALYSIS CONSIDERATIONS .............................................................. 10 
3.1 
ANALYSIS SET(S) ................................................................................................................... 10 
3.2 
STATISTICAL ANALYSIS ISSUES .................................................................................................. 10 
4. 
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE ......................................... 11 
5. 
GENERAL ANALYSIS METHODS ................................................................................... 11 
6. 
TRIAL PARTICIPANT DISPOSITION ............................................................................... 11 
6.1 
DISPOSITION OF PARTICIPANTS ......................................................................................... 11 
6.2 
TREATMENT EXPOSURE .......................................................................................................... 14 
6.3 
PROTOCOL DEVIATIONS ......................................................................................................... 14 
6.4 
UNPLANNED ENROLLMENT DISCONTINUATION ............................................................................ 15 
7. 
BASELINE DATA .......................................................................................................... 15 
8. 
PRIMARY ANALYSES ................................................................................................... 16 
8.1 
SAFETY ENDPOINT ANALYSIS ................................................................................................... 17 
8.2 
TOLERABILITY ENDPOINT ANALYSIS .......................................................................................... 17 
8.3 
ACCEPTABILITY ENDPOINT ANALYSIS ......................................................................................... 17 
8.3.1 
Completion of scheduled injections ......................................................................... 17 
8.3.2 
Preferred method for HIV prevention ...................................................................... 17 
9. 
SAFETY ANALYSES ...................................................................................................... 18 
9.1 
ADVERSE EVENTS AND DEATHS ................................................................................................ 18 
9.2 
LABORATORY EVALUATIONS .................................................................................................... 18 
9.3 
OTHER SAFETY MEASURES ...................................................................................................... 18 
10. 
IMMUNOGENICITY ANALYSES .................................................................................... 18 
11. 
PHARMACOKINETIC ANALYSES ................................................................................... 18 
12. 
SECONDARY ANALYSES .............................................................................................. 19 
13 
CHANGE HISTORY ....................................................................................................... 21 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 4 of 27 
 
 
14. APPENDIX A – ADVERSE EVENTS OF SPECIAL INTEREST ................................................... 22 
15. APPENDIX B – VARIABLE DEFINITIONS ............................................................................ 23 
16. APPENDIX C – IMPUTATION OF MISSING DATES ............................................................. 25 
 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 5 of 27 
 
 
1. LIST OF ABBREVIATIONS AND ACRONYMS  
Term/Abbreviation 
Definition 
ADaM 
Analysis Dataset Model 
AEs 
Adverse Events  
AESI 
AEs of Special Interest 
ALT 
Alanine Aminotransferase  
AST  
Aspartate Aminotransferase 
CAB LA 
Long-Acting Cabotegravir 
CABG 
Coronary Artery Bypass Grafting  
CASI 
Computer Assisted Self Interview 
CBC 
Complete Blood Count 
CMC  
Clinical Management Committee 
CPK 
Creatine Phosphokinase 
CRF  
Case Report Forms 
CV 
Coefficient of Variation 
DAIDS 
Division of AIDS 
EC  
Ethics Committee 
FDA  
(US) Food and Drug Administration 
GEE 
Generalized Estimating Equations 
HBsAg 
Hepatitis B Virus Surface Antigen 
HBV 
Hepatitis B Virus  
HDL  
High Density Lipoprotein 
IM 
Intramuscular 
IoR  
Investigator of Record 
IRB  
Institutional Review Board 
ISR 
Injection Site Reaction 
IUS 
Intrauterine System 
LDL 
Low Density Lipoprotein 
MO  
Medical Officer 
NIAID 
National Institute of Allergy and Infectious Diseases 
NICHD 
National Institute of Child Health and Human Development 
OHRP  
Office for Human Research Protections 
PTCA 
Percutaneous Transluminal Coronary Angioplasty 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 6 of 27 
 
 
SD 
Standard Deviation 
SMC 
Safety Monitoring Committee 
SPDSMP 
Study Progress and Data Safety Monitoring Plan 
STI 
Sexually Transmitted Infection 
Tbili 
Total Bilirubin  
ULN 
Upper Limit of Normal 
US 
United States 
WBC 
White Blood Cell 
WHO 
World Health Organization 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 7 of 27 
 
 
 
2. INTRODUCTION 
This SAP is intended to describe the final primary and secondary analyses upon completion of HPTN083-
01. Sections of the SCHARP SAP template had to be adapted here to reflect the distinct single-arm 
outcomes, as opposed to the more common multi-arm studies that the template was designed for. Key 
variable definitions are included in Appendix B. 
2.1 
General Design Considerations 
HPTN083-01 is a phase IIB single arm trial designed to establish the minimum safety, tolerability and 
acceptability data needed to support the use of cabotegravir long-acting injection (CAB LA) in an 
adolescent population, potentially transforming the field of HIV prevention for young people. The study 
target population is sexually active, healthy male adolescents aged below 18 years. The study target is to 
enroll more than 50 participants with at least 50 participants receiving at least one injection. Participant 
recruitment will take approximately 12 months. 
Study participation includes Step 1: a 5-week oral CAB 30mg QD safety lead-in followed by Step 2: a 
series of 5 intramuscular (IM) injections of 3 mL (600 mg) cabotegravir administered at 8-week intervals 
after a 4-week loading dose (injections at weeks 5, 9, 17, 25 & 33). Adherence support strategies (e.g., 
counseling, reminders, pill cases) will be included to support pill-taking during the first five weeks and to 
support retention during the injectable phase. A safety visit will follow each injection to ascertain 
pharmacokinetic-peak safety data, including injection site reactions. Step 3: A blood draw visit, the +8 
Week Visit, will follow the week 33 injection to monitor CAB drug levels. All participants who have 
received at least one injection will be followed for 48 weeks after their last injection. Waning levels of 
cabotegravir (the PK tail) will be covered with locally sourced oral TENOFOVIR/EMTRICITABINE 
(TRADE NAME: TDF/FTC, TRUVADA®) for daily use for 48 weeks. In Step 3 participants may also 
chose to continue with 8-week dosing of injectable of CAB-LA for 48 weeks (5 additional injections 
beyond the initial 5 injections, administered at weeks +8. +16, 24, +32, +40, and +48.) Behavioral and 
acceptability data will be collected via computer-assisted self-interview (CASI). Total participant 
commitment for the entire study is up to 87 weeks, or approximately 1.5 years. We anticipate recruitment 
for the study will take approximately 12 months. 
Participants who discontinue study product during Step 2 for any reason other than HIV infection or AE 
occurrence will be transitioned to open label TDF-FTC for 48 weeks. 
There are in total three study sites:  
• 
Adolescent and Young Adult Research at the Core Center (AYAR at CORE), Chicago, IL; 
• 
St. Jude Children’s Research Hospital CRS, Memphis, TN; 
• 
Fenway Health CRS, Boston, MA. 
Study is sponsored by Division of AIDS (DAIDS), United States (US) National Institute of Allergy and 
Infectious Diseases (NIAID), Eunice Kennedy Shriver National Institute of Child Health and Human 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 8 of 27 
 
 
Development (NICHD),US National Institutes of Health (NIH), IND number is 122,744. Protocol Chair 
is Sybil Hosek, PhD and Protocol Co-chair is Lynda Stranix-Chibanda, MBChB, MMED 
2.2 
Study Objectives and Endpoints 
Primary objectives:  
• 
To evaluate the safety, tolerability, and acceptability of CAB LA in healthy, HIV-uninfected male 
adolescents aged below 18 years. 
Secondary objectives: 
• 
To examine adherence to and timeliness of injections over time among adolescent participants 
provided CAB LA and information regarding its safety and efficacy.  
• 
To examine patterns of sexual risk behavior over time among adolescent participants provided 
CAB LA and information regarding its safety and efficacy. 
• 
To evaluate the safety of oral CAB during step 1 (oral phase) as well as all study products during 
the aggregate oral+injectable period for all enrolled participants. Additionally, we will include an 
intention to treat analysis for the primary safety endpoint.  
• 
To characterize the pharmacokinetics of CAB LA 
• 
Additional exploratory analyses will be done with the laboratory and clinical data, including 
resistance mutations 
 
To achieve the primary and secondary objective, the planned primary and secondary endpoints are:  
 
Primary endpoints: 
 
Safety endpoint: Proportion of participants experiencing any Grade 2 or higher clinical adverse events 
(AEs) and laboratory abnormalities among participants who receive at least one injection of CAB LA. 
Laboratory abnormalities include grade 2 or above on tests include (CRF: Chemistry Panel, Fasting Lipid 
Test Results, Urinalysis, Hematology): 
• 
Renal function: Creatinine, Creatinine clearance 
• 
Hematology: Hemoglobin, Platelets, WBC, Neutrophils, Lymphocytes 
• 
Liver function: Alkaline phosphatase, AST, ALT, Total bilirubin 
• 
Electrolytes: Phosphorus, Calcium 
• 
Other chemistries: CPK, Glucose, Amylase, Lipase,  
• 
Urine test: Protein, Glucose 
• 
Fasting Lipid Test Results: Total cholesterol, Triglycerides, LDL, HDL 
 
 
Tolerability endpoint: Proportion of participants who receive at least 1 injection and who discontinue 
receiving injections prior to the full course of injections due to intolerability of injection, frequency of 
injections or burden of study procedures. Reasons for intolerability may include:   
 
• 
Injection site reaction 
• 
Participant refused further participation1 
• 
Participant lost to follow-up 
• 
Participant is unwilling or unable to comply with required study procedures 
• 
Participant refused further study product use 
• 
Participant unable to adhere to visit schedule  
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 9 of 27 
 
 
1Excluding cases in which reason for termination is unrelated to intolerability 
  
Acceptability endpoints: Proportion of participants who complete all scheduled injections and proportion 
of participants who receive at least one injection who would consider using CAB LA for HIV prevention 
in the future. This endpoint will be evaluated using CASI questionnaires at the last injection visit (Step 2, 
week 33) for participants who do not have acceptability data at the Step 2, week 33 visit (either due to a 
change in when the questionnaire items were administered2, missed the final injection visit, or discontinue 
injections early) and continue to step 3, acceptability endpoints are evaluated during the follow up phase 
(step 3, week +12). The primary acceptability outcome is: 
If you wanted to protect yourself from getting HIV, which of the following product(s) would you 
prefer to use? 
• 
Prefer not using a product 
• 
Condoms only 
• 
Oral PrEP pills only 
• 
Injectable PrEP only 
• 
Condoms and oral PrEP pills together 
• 
Condoms and injectable PrEP together 
• 
Prefer not to answer 
 
 
Secondary endpoints: 
 
• 
Proportion of injection visits that occurred “on-time”  
o The target visit window for the week 5 injection is 0-3 days after the Week 5 visit date 
(allowing for the injection occurring on a different day from the W5 visit) and is +/-3 
days from the target injection date for all other injection visits. Visits happening within 
the target window are considered “on-time” 
• 
Change from enrollment of self-reported sexual behavior (number of sexual partners, increased 
episodes of anal sex without a condom) during the study period  
• 
Proportion of participants experiencing Grade 2 or higher clinical AEs and laboratory 
abnormalities in the oral phase and the aggregate over the entire study period   
• 
Plasma CAB pharmacokinetics 
2.3 
Randomization 
There is no treatment randomization as this study is a single arm, open label trial. 
2.4 
Blinding 
Participants and site staff will be unblinded throughout the trial. 
2.5 
Sample Size and Power 
The sample size for this protocol (n=50) is the number of participants agreed upon by the industry 
sponsor and regulators in order to provide supplementary safety and behavioral data on adolescents in 
collaboration with the HPTN 083 and HPTN 084 adult trials. The goal of the safety evaluation for this 
study is to identify safety concerns associated with CAB LA. 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 10 of 27 
 
 
 
 
 
 
 
 
Since each of the primary endpoints is a proportion, Table 2 shows the precision (confidence interval 
width) that will be obtained for each endpoint with a sample size of 50. 
Recognizing that some participants will not reach the first injection visit and/or may not receive any study 
injections due to personal or clinical concerns, the study will continue to recruit participants until it is 
clear that at least 50 participants will progress to the injection phase.  Experience in the parent study 
HPTN 083 suggests that only a small proportion of participants will fail to reach the injection stage, and it 
is expected that approximately 5-7 additional enrollees may be needed in order to reach 50 participants in 
the injection phase. 
3. GENERAL DATA ANALYSIS CONSIDERATIONS 
3.1 
Analysis Set(s) 
Primary and secondary analyses will be carried out among the following populations:  
 
Screened Population: Includes all participants who were screened for potential enrollment. 
 
Injection Population: Includes enrolled participants who receive at least one injection of CAB LA. 
 
Safety Population: Includes enrolled participants who began step 1 (oral phase). 
 
Enrolled Population: Includes all enrolled participants.  
 
Seroconverter Population: Includes all enrolled participants who seroconverted during the study. 
 
TDF/FTC Population: All enrolled participants who were provided TDF/FTC during the study.  
3.2 
Statistical Analysis Issues 
AEs will be tabulated using MedDRA preferred terms. The number and percentage of participants 
experiencing each specific AE (All AEs, Grade 2 or higher, and SAEs) will be tabulated by severity and 
by relationship to study product. For the calculations in these tables, each participant’s AEs will be 
counted once as the maximum severity and relationship to study product. AEs leading to temporarily or 
Table 2. Width of 95% confidence interval 
for estimated proportion as a function of 
the true proportion, assuming a sample size 
of 50. 
True proportion 
Width of 95% CI 
0.1 
± 0.083 
0.2 
± 0.11 
0.3 
± 0.13 
0.4 
± 0.14 
0.5 
± 0.14 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 11 of 27 
 
 
permanently stopping drug will also be summarized. Methods for imputation of missing dates are 
described in Appendix C   
4. INTERIM ANALYSIS AND DATA MONITORING COMMITTEE 
See: Study progress, data, and safety data monitoring plan (SPDSMP) for a detailed description of the 
safety monitoring committee (SMC) report and data and safety monitoring board (DSMB) report for this 
study.  
5. GENERAL ANALYSIS METHODS 
Within the single arm, all primary and secondary outcome proportions with 95% CIs will be calculated. 
6. TRIAL PARTICIPANT DISPOSITION 
6.1 
Disposition of Participants 
The study will recruit participants to ensure that at least 50 participants progress to the injection phase, 
therefore more than 50 participants will be screened and enrolled. 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 12 of 27 
 
 
Consort Diagram 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Screened    
n = x   
Enrolled   
n = x   
Excluded (x)   
· 
  Did not meet all inclusion 
criteria   (x)   
· 
  Declined to participate 
  (x)   
· 
  Lost to follow - up   (x)  
· 
  O ther  (x)   
Step 1   (Oral Phase )   
n = x   
visit 1: x/x (x%)   
visit 2: x/x (x%)   
Step 2 ( Injection Phase)   
n = x  
Injection 1: x/x (x%)  
Injection 2: x/x (x%)  
Injection 3: x/x (x%)  
Injection 4: x/x (x%)  
Injection 5: x/x (x%)  
Did not begin Step 2 (x) 
  
· 
 
Any HIV reactive/positive test 
  
(x) 
  
    
    
· 
 
Participant request   (x)   
· 
 
Product discontinuation due to 
disqualifying condition 
1 
 (x)  
· 
 
Lost to follow - up   (x)   
· 
 
O ther   (x)  
Step 3   (TDF/FTC)   
n = x   
visit 1 (+8wks): x/x (x%) 
  
visit 2 (+12wks): x/x (x%) 
  
visit 3 (+24wks): x/x (x%) 
  
visit 4 (+36wks): x/x (x%) 
  
visit 5 (+48wks): x/x (x%) 
  
  
 
Step 3 (CAB)
  
 
  
   
    
visit 1 (+8wks): x/x (x%) 
  
 
  
 
  
  
 
  
  
   
   
visit 2 (+16wks): x/x (x%) 
visit 5 (+40wks): x/x (x%)
visit 3 (+24wks): x/x (x%)
visit 4 (+32wks): x/x (x%)
visit 6 (+48wks): x/x (x%)
n = x 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 13 of 27 
 
 
1Conditions in Step 1 that could disqualify a participant from transitioning to Step 2 are as follows:  
• 
Pill count suggestive of less than 50% adherence at the Week 4 visit 
• 
Missed or delayed Week 4 visit 
• 
Grade 2 ALT at week 4, or grade 3 and above ALT anytime in step 1 
• 
Grade 3 AE that is related to study product anytime in step 1, excluding ALT & CPK 
• 
Grade 4 AE anytime in step 1, excluding ALT & CPK 
• 
Grade 3 and above CPK and < Grade 3 ALT 
• 
At substantial risk of HIV infection and/or qualifies for oral PrEP by local guidelines 
• 
Any HIV reactive/positive test 
 
Participant enrollment inclusion and exclusion criteria (see study protocol)  
A. Inclusion Criteria 
1) Assigned male at birth (including MSM, TGW, and gender non-conforming people) 
2) At enrollment, below 18 years of age 
3) At enrollment, body weight ≥ 35 kg (77 lbs.) 
4) Willing to provide written informed assent/consent for the study and/or able to obtain written 
parental/guardian informed consent 
5) Self-reported sexual activity with a male in the past 12 months 
6) In general, good health, as evidenced by the following laboratory values:  
a. Non-reactive / negative HIV test results  
b. Absolute neutrophil count > 799 cells/mm3 
c. Platelet count ≥ 100,000/mm3 
d. Hemoglobin > 11g/dL 
e. Calculated creatinine clearance ≥ 60 mL/minute using the modified Schwartz equation (≤ 
grade 2) 
f. Alanine aminotransferase (ALT) < 2.0 times the upper limit of normal (ULN) and total 
bilirubin (Tbili) ≤ 2.5 x ULN 
g. Hepatitis B virus (HBV) surface antigen (HBsAg) negative and accepts vaccination 
h. HCV Antibody negative 
7) Willing to undergo all required study procedures 
8) If currently on PrEP from a non-study source, willing to stop said PrEP prior to enrollment and 
agree to switch to oral CAB for the lead-in period and CAB LA injections.  
 
B. Exclusion Criteria 
1) Co-enrollment in any other HIV interventional research study or other concurrent studies which 
may interfere with this study (as provided by self-report or other available documentation); 
2) Past or current participation in HIV vaccine trial with exception for participants who can provide 
documentation of receipt of placebo; 
3) Exclusively had sex with biological females in lifetime; 
4) In the last 6 months (at the time of screening):  
• 
active or planned use of any substance use which would, in the opinion of the site investigator, 
would hinder study participation (including herbal remedies), as described in the IB or listed in 
the SSP, and/or Protocol Section 4.4 
5) Known history of clinically significant cardiovascular disease, as defined by history/evidence of 
symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 14 of 27 
 
 
percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac 
disease; 
6) Inflammatory skin conditions that compromise the safety of intramuscular (IM) injections;  
7) Tattoo or other dermatological condition overlying the buttock region that may interfere with 
interpretation of injection site reactions;  
8) Current or chronic history of liver disease (e.g., non-alcoholic or alcoholic steatohepatitis) or 
known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome, asymptomatic 
gallstones, or cholecystectomy);  
9) Known history of clinically significant bleeding;  
10) Surgically-placed or injected buttock implants or fillers, per self-report. Contact the CMC for 
guidance regarding questions about individual cases 
11) A history of seizure disorder, per self-report;  
12) Medical, social or other condition that, in the opinion of the site investigator, would interfere with 
the conduct of the study or safety of the participant (e.g., provided by self-report, or found upon 
medical history and examination or in available medical records);  
13) Plans to move out of the geographic area within the next 18 months or otherwise unable to 
participate in study visits, according to the site investigator. 
 
6.2 
Treatment Exposure 
During step 1 (oral phase) staff are required to observe participants take one pill at enrollment, week 2 
and week 4. Pill counts will occur at visits for week 2 and 4.  
 
All injections during step 2 (injection phase) will be administered (and therefore directly observed) by 
study staff. Injections will be considered “on-time” if they occur in the visit window, described in the 
secondary analyses (section 12).  
 
Blood samples will be collected throughout the study from all participants and assayed for plasma CAB 
concentrations. PK sample times include pre-dose trough samples at W5, W9, W17, W25, and W33 
(final concentration in injection phase), 1-week post injection samples at W6, W10, W18, W26, 
W34, with a final sample at +8-weeks following the final injection. For participants advancing to Step 3 
and do not elect to continue with CAB injections, additional follow-up samples will be collected at +24, 
+36 and +48-weeks following the final injection and at the HIV confirmatory visit. 
6.3 
Protocol Deviations 
Protocol deviations will be summarized in regular reports to the SMC, the details of which are available 
in the SPDSMP.  Serious protocol deviations may result in participants being terminated from the trial 
and/or being excluded from analyses.  The decision to exclude participant data from the analyses will be 
made based on independent review.  Deviations resulting in failure to progress to the injection phase 
would exclude such participants from the pertinent analysis datasets (except for the secondary safety 
analyses, which are limited to the oral phase only).  
 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 15 of 27 
 
 
6.4 
Unplanned enrollment discontinuation 
In January 2022 the HPTN leadership determined that the study accrual rate was insufficient to meet the 
target enrollment in a reasonable amount of time, and study enrollments were stopped after a total accrual 
of nine participants.  
 
7. BASELINE DATA  
 
The following data will be described overall, and by site: 
 
Demographics (Table 1): 
• 
Age (continuous – mean, SD, median, min max; categorical (≤16, > 16): n (%) ) 
• 
Gender identity 
• 
Race  
• 
BMI 
o Age standardized BMI z-score (continuous – mean, SD, median, min max) 
o Classification as obese, overweight, normal, thinness, severe thinness based on z-score 
▪ 
Note: The Clinical Study Report will report BMI without the use of z-scores 
• 
Housing security* 
o Do you have a regular place or home where you stay and store your things? (yes/no) 
• 
Food security* 
o In the past 6 months, how frequently did you worry that your household would not have 
enough food? 
 
Sexual behaviors / HIV Risk Perception (Table 2): 
   During the past month the participant had*:  
o a primary partner  
o transactional sex with male sex partners  
o # male and/or transgender female sex partners  
o # male and/or transgender female sex partners who are reported to be HIV positive 
o # episodes of receptive anal sex  
o # episodes of receptive anal sex without condom  
o # episodes of receptive anal sex without condom, with HIV+ or unknown partner 
o # episodes of insertive anal sex  
o # episodes of insertive anal sex without condom  
o # episodes of insertive anal sex without condom, with HIV+ or unknown partner 
 
• 
STIs present at enrollment: 
o Gonorrhea  
o Trachomatis 
o Syphilis 
• 
Hepatitis testing at screening/enrollment 
o HBV 
o HCV 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 16 of 27 
 
 
• 
HIV risk perception*:  
o How much do you personally feel at risk of getting infected with HIV? 
 
Mental health (Table 3): 
• 
Depression indices1 
o CES-D-10* (continuous – mean, SD, median, min max; categorical (≤10: not depressed, 
>10: depressed): n (%)) 
o PHQ9 (continuous – mean, SD, median, min max; categorical (none-minimal, mild, 
moderate, moderately severe, severe): n (%)) 
• 
Intimate partner violence (IPV)* 
o In the past 6 months, have any of your partners punched, slapped, kicked, bit you, or 
caused you any type of physical harm? 
o In the past 6 months, have any of your partners insulted, ignored or humiliated you, 
yelled at you, or made you feel ashamed or bad about yourself? 
o In the past 6 months, have any of your partners forced you to have sex or perform any 
sexual act, or touched you sexually in any way that you did not want? 
o In the past 6 months, have any of your partners made you feel afraid, unsafe or in danger? 
• 
Primary care post-traumatic stress disorder screening questionnaire (PC-PTSD-4)* (continuous – 
mean, SD, median, min max; categorical (≤2: no PTSD, >2: potential PTSD): n (%)) 
o Note: The Clinical Study Report will not include this summary of PC-PTSD-4 
• 
alcohol/substance use* 
o How often do you have a drink containing alcohol? 
o How often do you have six or more drinks on one occasion? 
o In the past month, did you have a drink containing alcohol just before or during sex? 
o In the past month, how often have you used each of the following substances? 
▪ 
Cannabis (Also called marijuana, pot, grass, dakka, dagga or hash) 
▪ 
Amphetamine-type stimulants (For example Tik/Crystal Meth, ecstasy, speed, or 
diet pills) 
▪ 
Prescription drugs for non-prescription purposes (For example codeine (including 
cough syrup), efavirenz, valium) 
 
1Internal consistency of Depression Index summaries (addendum to Table 3): 
1. Tabular cross-frequency of the categories for CES-D-10/PHQ9 
2. Scatterplot of the values of either index, with color-coding based on whether they agree on 
qualitative risk of depression 
a. Note: The internal consistency evaluations will not be included in the Clinical Study 
Report 
 
*CASI questionnaire variables 
8. PRIMARY ANALYSES 
For each of the three primary endpoints the number and proportion of participants will be computed along 
with corresponding 95% confidence intervals.  Each summary will be provided both overall and by site. 
Endpoint descriptions are available in section 2.2. 
 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 17 of 27 
 
 
8.1 
 Safety endpoint analysis 
 
Cohort: Injection population 
Analysis description: Number and percent of participants experiencing any Grade 2 or higher 
clinical adverse events (AEs) or laboratory abnormalities (reported as adverse events) from the 
first injection visit to 8 weeks after the last Step 2 injection visit, or Week 41, whichever comes 
first.  See Section 3.2 for details regarding aggregation and tabulation of AEs. 
 
8.2 
Tolerability endpoint analysis 
 
Cohort: Injection population 
Analysis description: Number and percent of participants who receive at least 1 injection and who 
discontinue receiving injections prior to the full course of injections due to intolerability of 
injection or burden of study procedures. Reasons for intolerability may include:    
a. Injection site reaction 
b. Burden of study procedure 
i. 
Participant refused further participation 
ii. 
Participant is unwilling or unable to comply with required study procedures 
iii. 
Participant refused further study product use 
iv. 
Participant unable to adhere to visit schedule  
 
8.3 
Acceptability endpoint analysis 
 
8.3.1 
Completion of scheduled injections  
 
Population: Injection population and Enrolled population 
Analysis description: Number and percent of participants who complete all scheduled injections1  
 
1Definition of completing all scheduled injections for participants who are confirmed 
HIV positive or discontinue product due to the following reasons: 
• 
Death 
• 
Early study closure 
• 
HBV infection 
 
During Step 1: 
Enrolled population: completed all 0 of 0 scheduled injections 
Injection population: not applicable, did not receive injection 
 
During Step 2: 
Both enrolled and injection populations: completed all injections whose target window 
closed prior to death/seroconversion/product discontinuation date   
 
 
8.3.2 
Preferred method for HIV prevention 
 
 
Population: Injection population  
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 18 of 27 
 
 
Analysis description: Number and percent of participants who choose ‘injectable PrEP’ or 
‘condoms and injectable PrEP’ when asked the question “If you wanted to protect yourself 
from getting HIV, which of the following product(s) would you prefer to use?” 
9. SAFETY ANALYSES  
See section 8.1 above.  In addition to the primary safety outcomes (grade 2 or higher), AEs and laboratory 
data will be summarized in the closed DSMB report (described in the SPDSMP). 
9.1 
Adverse Events and Deaths  
Adverse events of special interest (AESI) will be summarized in the Clinical Study Report. Planned AESI 
summaries for the CSR are described in Appendix A. 
9.2 
Laboratory Evaluations  
Population: Safety population 
Description: Laboratory findings for CBC (hemoglobin, platelets, WBC, neutrophils, lymphocytes), 
chemistries (urea, creatinine, CPK, glucose, calcium, phosphorous, amylase, lipase), liver function (AST, 
ALT, total bilirubin, alkaline phosphatase) and fasting lipid profile (total cholesterol, triglycerides, HDL, 
LDL) will be reported by grade, as defined in the “Division of AIDS (DAIDS) Table for Grading the 
Severity of Adult and Pediatric Adverse Events”.  The proportion of laboratory findings qualifying as 
Grade 2 or above will be presented. Baseline laboratory values will be summarized by site using: median, 
1st and 3rd quartiles, and min and max. Change from baseline in laboratory values will be summarized at 
follow up visits using: median, and 1st and 3rd quartile. Summaries involving values and changes from 
baseline at scheduled visit time points will consider values from scheduled visits only, and in the case of 
missing values, results will not be carried forward from interim (unscheduled) visits.  For summaries and 
analyses involving changes in laboratory values over time or maximum change from baseline (e.g. shift 
tables), values from interim (unscheduled) visits will also be considered. 
9.3 
Other Safety Measures  
10. IMMUNOGENICITY ANALYSES 
NA 
11. PHARMACOKINETIC ANALYSES 
Plasma will be collected during Steps 1 and 2 for pharmacologic assessment of CAB concentrations.  
Plasma and DBS will also be collected in Step 3, and if a study participant seroconverts, for potential 
pharmacologic analysis of plasma TFV and DBS TFV-DP concentrations, respectively, to assess PrEP 
adherence, and for potential HIV genotyping. Analysis details are provided in the current version of the 
Pharmacokinetics Analysis Plan  
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 19 of 27 
 
 
12. SECONDARY ANALYSES  
For binary secondary endpoints, the number and proportion of endpoints will be computed along with 
corresponding 95% confidence intervals.  Each summary will be provided both overall and by site. CSR 
analysis will be only summarized overall. Endpoint descriptions are available in section 2.2. 
 
12.1 Plasma CAB pharmacokinetics 
Analysis details are provided in the current version of the Pharmacokinetics Analysis Plan  
 
12.2 Proportion of participants experiencing Grade 2 or higher clinical AEs and laboratory 
abnormalities in the oral phase and over the entire study period 
 
Cohort: Safety population 
Analysis description: Number and percent of participants experiencing any Grade 2 or higher 
clinical adverse events (AEs) or laboratory abnormalities from:  
1. enrollment to week 5 (oral phase (step 1), including interim visits). 
2. enrollment to 8 weeks following the last injection received (aggregate over oral+injection 
phases (step 1-step 2) including interim visits) 
 
12.3 Proportion of participants receiving one or more injections who experience Grade 2 or 
higher clinical AEs and laboratory abnormalities from initial injection to 36 weeks later 
 
Population: Injection population 
Analysis description: Number and percent of participants experiencing any Grade 2 or higher 
clinical adverse events (AEs) or laboratory abnormalities from the first injection visit to 
approximately 36 weeks later regardless of whether participants received all 5 injections. For 
participants receiving all 5 injections, the end date is 8 weeks following the week 33 injection 
visit. For participants discontinuing study product early and moving on to Step 3, the end date is 
36 weeks after the initial injection. Participants who terminate early are included in the analysis 
and censored at the date of termination. 
 
 
12.4 Proportion of injection visits that occurred “on-time” 
Population: Injection population 
Analysis description: Number and percent of injection visits (up to 5 per participant) that occur 
“on-time”1, using the number of injections given as the denominator. This will be presented along 
with the total number and percent of injections given, among all intended injections (i.e. 5 
injections per participant).  
 
1The target injection date is defined by the W5 visit i.e. for the initial injection, the target 
injection date is 0 days (same day), and is +28, +84, +140, +196 days from the W5 visit for 
injections 2-5, respectively. The target visit window for injection visits for the week 5 injection is 
0 to 3 days after the W5 visit (if the injection could not be done on the same day as the W5 visit), 
for all other injection visits (W9, W17, W25, W33) the target window is +/-3 days from the target 
injection date. Injection dates happening within the target window are considered “on-time”. 
 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 20 of 27 
 
 
12.5 Change from enrollment of self-reported sexual behavior (number of sexual partners, and 
number of episodes of anal intercourse without a condom) during the study period 
 
Note: This secondary analysis will not be included in the Clinical Study Report. 
 
Population: Enrolled population 
Analysis description: Counts of sexual partners and episodes of anal intercourse without a 
condom will be summarized (mean and median) at enrollment and each regular Step 1 and Step 2 
follow-up visit (W4, W5, W9, W17, W25, W33, +8).  
 
12.6 Evaluate rates of HIV drug resistance among participants who acquire HIV infection 
during the study 
 
Population: Seroconverter population 
Analysis description: Data from steps 1, 2, and 3 will be included. The number of cases of drug 
resistance will be summarized. All cases of drug resistance among incident HIV infections will be 
described. 
 
 
 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 21 of 27 
 
 
13 CHANGE HISTORY  
Version 
Affected 
Section(s) 
Activity Description 
Number 
Effective 
Date 
1.0 
02/20/2021 
All sections 
First version of SAP was developed.  
2.0 
Date of 
last 
signature 
2, 3, 6, 7-9, 
11, 12, 13, 
16, 17 
Revisions based on new option to continue CAB injections 
during Step 3. Added study populations and definitions. 
Updated consort diagram, primary and secondary 
outcomes/analyses, including addition of secondary 
outcome 12.6. Updated acceptability endpoint definition, 
and reference to PK analysis plan. Additional details to 
account for changes to schedule of visits and data 
collection, due to new CAB option in Step 3. Added 
sections: 13 (ad hoc analysis), appendices A, B and C (AEs 
of special interest, variable definitions and imputation of 
missing data).  Most revisions are designed to harmonize 
with HPTN 084-01 SAP 3.0. 
 
 
 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 22 of 27 
 
 
14. APPENDIX A – Adverse Events of Special Interest 
Adverse events of special interest (AESI) have been determined for CAB based on pre-clinical and 
clinical experience, along with information for the integrase inhibitor class of HIV medications safety 
profile. These are adverse events for which more detailed summaries of event characteristics are of 
interest. 
The identification and classification of AESI will be based on MedDRA preferred terms as specified in 
the ADRG (Analysis Data Reviewers Guide).  The current MedDRA version used for the preferred terms 
in the ADRG is v25.1.  Preferred terms will be updated in the ADRG if a new version becomes available 
before the database lock. 
Table 1 below shows the adverse events of special interest identified and reasons for including. 
 
Table 1 Adverse Events of Special Interest (Clinical Study Report only) 
AESI 
Product Implicated Reason for Including as AESI 
Hepatic Safety Profile: Assessment of risk of 
hepatoxicity 
CAB 
Clinical, Class, Regulatory 
Interest,  
Hypersensitivity Reactions (HSR) 
CAB 
Class, Regulatory Interest,  
Rash 
CAB 
Class, Regulatory Interest 
Neuropsychiatric Events  
• 
Suicidal Ideation/Behavior 
• 
Depression 
• 
Bipolar Disorder 
• 
Psychosis 
• 
Mood Disorders 
• 
Anxiety 
• 
Sleep Disorders 
CAB 
Clinical, Class, Regulatory 
Interest,  
Injection Site Reactions (ISR) 
CAB 
Clinical, Regulatory Interest 
Seizures and Seizure-like events 
CAB 
Clinical, Regulatory Interest 
Weight Gain 
CAB 
Clinical, Class, Regulatory 
Interest 
Rhabdomyolysis 
CAB 
Clinical, Class, Regulatory 
Interest 
Pancreatitis 
CAB 
Clinical, Therapeutic Area, 
Regulatory Interest 
Impact on Creatinine 
CAB 
Regulatory Interest, 
Therapeutic Area  
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 23 of 27 
 
 
Hyperglycemia/new onset diabetes mellitus 
CAB 
Observation from 083, Class 
  
Common ISR adverse events are defined by MedDRA preferred terms including injection site pain, 
injection site induration, injection site nodules and preferred terms of any other ISR exceeding the threshold 
as specified in the ADRG. ISRs will be explored regardless of IP relationship.  
Each one of the AESIs described in Table 3 will be explored via the data listings in more detail. Listings 
will summarize Adverse events that occurred during Step 1 and/or Step 2 of the study and will contain 
information to assess the following.  
Event Characteristics: The characteristics of all event occurrences during the post-baseline period will 
look at event characteristics (serious, drug-related, leading to withdrawal, or Grade 3/4, fatal), number of 
events per participant, outcome, maximum grade or intensity and action taken.  
Time to First Event (TTFE) and Duration of Events: Time of onset and duration of event will be 
provided.  
 
In addition, Pyrexia Plus includes PT: (Chills – 10008531, Feeling of Body Temperature Change - 
10061458, Feeling Hot - 10016334, Body Temperature Increased - 10005911, Pyrexia - 10037660, 
Influenza Like Illness - 10022004, Fever – 10016558) events will be looked at in relation to timing of 
previous injection. 
No formal summaries or statistical comparisons are planned for AESI.  
 
15. APPENDIX B – Variable Definitions 
1. CES-D-10 (score/categories)  
 
Create a score based on 10 items below (in CASI questionnaire): 
 
In the list below, please indicate how often you have felt this way during the past week by ticking the 
appropriate box for each question: 
 
1. I was bothered by things that usually don't bother me. 
2. I had trouble keeping my mind on what I was doing. 
3. I felt depressed. 
4. I felt that everything I did was an effort. 
5. I felt hopeful about the future. 
6. I felt fearful or afraid. 
7. My sleep was restless. 
8. I was happy. 
9. I felt lonely. 
10. I could not "get going”, I did not feel motivated. 
 
Scoring: 
 
Rarely or none of the 
time (less than 1 day) 
Some or a little of the 
time (1‐2 days) 
Occasionally or a moderate 
amount of time (3‐4 days) 
All of the time 
(5‐7 days) 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 24 of 27 
 
 
Questions 
5 & 8 
3 
2 
1 
0 
All other 
questions 
0 
1 
2 
3 
 
The total score is calculated by finding the sum of 10 items. Score as ‘missing’ if 1 or more items are 
missing/prefer not to answer. Any score ≥10 is considered depressed. 
 
2. PHQ-9 (score/categories)  
 
Create a score based on values from 9 questions (Not at all = 0, Several days = 1, More than half the days 
= 2, Nearly every day = 3): 
 
    Over the last 2 weeks, how often have you been bothered by the following problems? 
 
1. Little interest or pleasure in doing things 
2. Feeling down, depressed, or hopeless 
3. Trouble falling or staying asleep, or sleeping too much 
4. Feeling tired or having little energy 
5. Poor appetite or overeating 
6. Feeling bad about yourself - or that you are a failure or have let yourself or your family down", 
7. Trouble concentrating on things, such as reading the newspaper or watching television", 
8. Moving or speaking so slowly that other people could have noticed. Or the opposite - being so 
fidgety or restless that you have been moving around a lot more than usual 
9. Thoughts that you would be better off dead, or of hurting yourself 
 
PHQ-9 score obtained by adding score for each question (total points). Score as ‘missing’ if 1 or more 
items are missing. Then categories of depression severity are created from the total score according to: 0-
4: None-minimal, 5-9: Mild, 10-14: Moderate, 15-19: Moderately Severe 20 – 27: Severe.  
 
3. PC-PTSD-4 (score/categories)  
 
Create a score based on values from 4 questions (yes = 1, no = 0): 
 
In your life, have you ever had any experience that was so frightening, horrible, or upsetting that, in the 
past month, you: 
 
1. Have had nightmares about it or thought about it when you did not want to? 
2. Tried hard not to think about it or went out of your way to avoid situations that reminded you of it? 
3. Were constantly on guard, watchful, or easily frightened? 
4. Felt empty, numb or detached from others, activities, or your surroundings? 
If missing or prefer not to answer any questions, then code score as missing. For non-missing scores, a 
score of 0-2 fails to indicate PTSD, and ≥ 3 indicates the potential for PTSD, which can be determined by 
a clinical interview.  
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 25 of 27 
 
 
 
4. Age-standardized BMI z-score 
 
Based on World Health Organization (WHO) tool:  
 
(1)      https://www.who.int/tools/growth-reference-data-for-5to19-years/indicators/bmi-for-age.  
 
With instructions for calculations (see section “Computation of centiles and z-scores”, link to pdf: 
“instructions in English”): 
 
(2)      https://cdn.who.int/media/docs/default-source/child-growth/growth-reference-5-19-
years/computation.pdf?sfvrsn=c2ff6a95_4 
 
 
Age-specific values of necessary parameters L(t), M(t), and S(t) can be downloaded from the website (1) 
(see section: “Expanded tables for constructing national health cards” link to dataset “z-scores: 
girls”)  
 
Categorical BMI classification based on age-standardized BMI z-score as follows:  
• 
Obesity: >+2 
• 
Overweight: >+1 and ≤+2 
• 
Normal: >-2 and ≤+1 
• 
Thinness: >-3 and ≤-2 
• 
Severe thinness: ≤-3 
16. APPENDIX C – Imputation of missing dates 
Missing Start and Stop Dates for Prior and Concomitant Medication, and Medical History 
 
The Assumption is to consider the most conservative judgment when imputing. 
 
Start date: 
When imputing a start date ensure that the new imputed date is sensible i.e. is prior to the end 
date and the general rules are: 
1. If start date is completely missing, start date will not be imputed 
2. If year and month are present and day is missing, set day to the 1st day of month.  
3. If year and day are present and month is missing, then set month to January. 
4. If year is present and month and day are missing, set month and day to January 1st.  
 
Stop date: 
1. If end date is completely missing, end date will not be imputed 
2. If year and month are present and day is missing, set day to the last day of month. 
3. If year and day are present and month is missing, set month to December 
4. If year is present and month and day are missing, set month and day to December 31st. 
 
Missing Start and Stop Dates for Adverse Events (including ISRs) 
 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 26 of 27 
 
 
The Assumption is to consider the most conservative judgment when imputing. 
 
Start date: 
1. If start date is completely missing, start date is set to date of first dose. 
2. If (year is present, and month and day are missing) or (year and day are present, and month is 
missing): 
a. If year = year of first dose, then set month and day to month and day of first dose. 
b. If year < year of first dose, then set month and day to December 31st. 
c. If year > year of first dose, then set month and day to January 1st. 
3. If month and year are present and day is missing: 
a. If year = year of first dose and 
i. If month = month of first dose, then set day to day of first dose date. 
ii. If month < month of first dose, then set day to last day of month. 
iii. If month > month of first dose, then set day to 1st day of month. 
b. If year < year of first dose, then set day to last day of month. 
c. If year > year of first dose, then set day to 1st day of month. 
 
Stop date: 
If the outcome of the AE was ongoing or unknown, then the rules outlined below will not be applied. 
 
1. If stop date is completely missing, stop date is set to date of study discontinuation. 
2. If (year is present, and month and day are missing) or (year and day are present, and month is 
missing): 
a. If year = year of study discontinuation, then set month and day to month and day of study 
discontinuation. 
b. If year < year of study discontinuation, then set month and day to December 31st. 
c. If year > year of study discontinuation, then set month and day to December 31st. 
3. If month and year are present and day is missing: 
a. If year = year of study discontinuation and 
i. If month = month of study discontinuation, then set day to day of study 
discontinuation date 
ii. If month < month of study discontinuation, then set day to last day of month. 
iii. If month > month of study discontinuation, then set day to last day of month. 
b. If year < year of study discontinuation, then set day to last day of month. 
c. If year > year of study discontinuation, then set day to last day of month. 
 
Missing Start and Stop Dates for Protocol Deviations 
The Assumption is to consider the most conservative judgment when imputing. 
 
Start date: 
When imputing a start date ensure that the new imputed date is sensible i.e. is prior to the end date 
and the general rules are: 
 
1. If start date is completely missing, start date will not be imputed 
2. If (year is present, and month and day are missing) or (year and day are present, and month is 
missing), set month and day to January 1st. 
3. If year and month are present and day is missing, set day to the 1st day of month.  
 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


 
 
 
 
 
 
Confidential 
 
All proprietary rights reserved 
Page 27 of 27 
 
 
Stop date: 
1. If end date is completely missing, end date will not be imputed 
2. If (year is present, and month and day are missing) or (year and day are present, and month is 
missing), set month and day to December 31st. 
3. If year and month are present and day is missing, set day to the last day of month. 
 
 
 
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024


Signature Page for SCHARP-TMF-32741 v2.0
Signature Page for SCHARP-TMF-32741 v2.0
Reason for signing: Approved
Name: Xu Guo
Role: Data Analytics
Date of signature: 17-Jan-2023 19:54:18 GMT+0000
Reason for signing: Approved
Name: Brett Hanscom
Role: Hutch SDMC
Date of signature: 17-Jan-2023 23:02:14 GMT+0000
HPTN083-01 Statistical Analysis Plan 17 Jan 2023 | SCHARP-TMF-32741 | 2.0
Approved
Downloaded by Xu Guo on 27 Aug 2024