HPTN 071 Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART): A cluster-randomized trial of the impact of a combination prevention package on population-level HIV incidence in Zambia and South Africa A Study of the HIV Prevention Trials Network DAIDS ID: 11865 Sponsored by: Division of AIDS, National Institute of Allergy and Infectious Diseases U.S. National Institutes of Health Funded by: National Institute of Allergy and Infectious Diseases National Institute of Mental Health Office of the United States Global AIDS Coordinator Bill and Melinda Gates Foundation U.S. National Institutes of Health Protocol Chair: Richard Hayes London School of Hygiene & Tropical Medicine London, United Kingdom Protocol Co-Chair: Sarah Fidler Imperial College London, United Kingdom Final Version 3.0 16 November 2015 Non-IND Study HPTN 071 Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART): A cluster-randomized trial of the impact of a combination prevention package on population-level HIV incidence in Zambia and South Africa TABLE OF CONTENTS LIST OF TABLES AND FIGURES ............................................................................................... 6 LIST OF ABBREVIATIONS AND ACRONYMS ........................................................................ 7 PROTOCOL TEAM ROSTER ....................................................................................................... 9 INVESTIGATOR SIGNATURE PAGE....................................................................................... 15 SCHEMA ...................................................................................................................................... 16 OVERVIEW OF STUDY DESIGN AND RANDOMIZATION SCHEME ................................ 19 1.0 INTRODUCTION ............................................................................................................. 20 1.1 Background and Prior Research ...................................................................................... 20 1.2 Rationale .......................................................................................................................... 20 1.2.1 The HIV Epidemic in Sub-Saharan Africa............................................................... 21 1.2.2 HIV Prevention Methods.......................................................................................... 22 1.2.3 Anti-Retroviral Therapy (ART) for HIV Prevention ............................................... 24 1.2.4 Innovation ................................................................................................................. 26 2.0 STUDY OBJECTIVES AND DESIGN ............................................................................ 29 2.1 Primary Objective ............................................................................................................ 29 2.2 Secondary Objectives ...................................................................................................... 29 2.3 Study Design .................................................................................................................... 31 2.4 Timing of Deployment of Intervention and Research Components ................................ 33 2.5 Cross-Sectional HIV Incidence Estimation ..................................................................... 35 3.0 STUDY INTERVENTION ............................................................................................... 35 3.1 Implementation Team Experience ................................................................................... 35 3.2 Description of CHiP Teams ............................................................................................. 36 3.3 Universal HIV Testing and Linkage to Care ................................................................... 36 3.4 Male Circumcision........................................................................................................... 37 3.5 Universal Treatment ........................................................................................................ 37 3.5.1 Choice of ART Regimen .......................................................................................... 38 3.6 Treatment According to Local Guidelines (Arms B & C) .............................................. 38 3.7 Prevention of Mother-to-Child Transmission .................................................................. 39 3.8 Management of Sexually Transmitted Infections ............................................................ 39 3.9 Screening and Referral for TB ......................................................................................... 39 3.10 Provision of PrEP ......................................................................................................... 40 3.11 Standard of Care........................................................................................................... 40 3.12 Delivery of Intervention ............................................................................................... 40 3.12.1 Activities with Local Health Centers/Community Institutions ................................ 40 3.12.2 Collaborations .......................................................................................................... 41 3.13 Monitoring and Evaluation Plan .................................................................................. 43 4.0 STUDY POPULATION.................................................................................................... 45 4.1 Description/Selection of the 21 Study Communities....................................................... 45 HPTN 071 Version 3.0 Page 2 of 166 16 November 2015 4.2 Randomization ................................................................................................................. 48 4.3 Community Engagement ................................................................................................. 48 5.0 RESEARCH PROCEDURES AND ACTIVITIES .......................................................... 49 5.1 Population Cohort ............................................................................................................ 50 5.1.1 Sampling/Recruitment of Population Cohort .......................................................... 50 5.1.2 Inclusion Criteria Population Cohort ....................................................................... 50 5.1.3 Exclusion Criteria Population Cohort ...................................................................... 50 5.1.4 Procedures and Activities ......................................................................................... 51 5.1.5 Reviewing Health Center Records for Population Cohort ...................................... 52 5.1.6 Retention in Population Cohort ............................................................................... 52 5.2 Population Cross-Sectional Survey (if funded) ............................................................... 53 5.2.1 Sampling/Recruitment of Population Cross-Sectional Survey Participants ............ 53 5.2.2 Inclusion Criteria ...................................................................................................... 53 5.2.3 Exclusion Criteria ..................................................................................................... 53 5.2.4 Procedures and Activities ......................................................................................... 54 5.3 Case-Control Studies ....................................................................................................... 54 5.3.1 Case-Control Study 1 - Uptake of Testing in the First Round of Home-Based Testing Provided by CHiP Teams in Arms A & B ................................................................ 54 5.3.1.1 Sampling/Recruitment of Case-Control Study 1 Participants........................... 55 5.3.1.2 Inclusion Criteria Case-Control Study 1 ........................................................... 55 5.3.1.3 Exclusion Criteria Case-Control Study 1 .......................................................... 55 5.3.1.4 Procedures and Activities.................................................................................. 55 5.3.2 Case-Control Study 2 - Uptake of Immediate Treatment in Arm A ........................ 55 5.3.2.1 Sampling/Recruitment of Case-Control Study 2 Participants........................... 56 5.3.2.2 Inclusion Criteria Case-Control Study 2 ........................................................... 56 5.3.2.3 Exclusion Criteria Case-Control Study 2 .......................................................... 56 5.3.2.4 Procedures and Activities.................................................................................. 56 5.3.3 Case-Control Study 3 - Uptake of Testing in the Second Round of Home-Based Testing Provided by CHiP Teams in Arms A & B ................................................................ 57 5.3.3.1 Sampling/Recruitment of Case-Control Study 3 Participants........................... 57 5.3.3.2 Inclusion Criteria Case-Control Study 3 ........................................................... 57 5.3.3.3 Exclusion Criteria Case-Control Study 3 .......................................................... 57 5.3.3.4 Procedures and Activities.................................................................................. 57 5.4 Qualitative Studies ..........................................................................................................