Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART)

Study Overview
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Brief Summary
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PopART is a community randomized trial that is investigating whether a community-wide combination HIV prevention package including annual home-based HIV testing, active referral and the offer of immediate ART for those testing HIV-positive, along with the promotion of proven HIV prevention methods (such as voluntary medical male circumcision, prevention of mother to child transmission and condom use), will help to prevent transmission and substantially reduce new HIV infections. The study is being conducted in 21 communities in Zambia and South Africa (randomized into 3 arms, each with 7 communities) with a total population of approximately 1.2 million individuals.

Detailed Description
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HIV Prevention Trials Network (HPTN) 071 (PopART) will investigate the impact on HIV incidence of universal voluntary HIV counseling and testing (with referral to care) provided to a community through a house-to-house campaign, in combination with early ART for individuals who are HIV-positive, and other proven preventive interventions. The design of HPTN 071 (PopART) will allow the study team to distinguish between the impact of universal testing with referral for HIV care in accordance with national guidelines, and the impact of universal testing with referral for early ART initiation for those with HIV infection. In addition, HPTN 071 (PopART) will determine if a program of universal voluntary testing, including early ART initiation, is feasible and acceptable when delivered on a large scale to entire communities. Evaluating the effectiveness of universal voluntary HIV counseling and testing with the offer of early ART is a key global health priority.

Official Title
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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

Conditions
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HIV

Intervention / Treatment
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* Other: Universal Testing with immediate ART
* Other: Universal Testing with ART eligibility according to National Guidelines
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Population Cohort 18 - 44 years of age Able and willing to provide informed consent Residing within catchment area of a designated local health unit and intending to remain so for the next three years Residing in a randomly selected household Case-Control Study 1 Inclusion Criteria: At least 18 years of age Able and willing to provide informed consent Resident in the cluster during the first round of testing Visited by a CHiP team and offered testing during the first round of home-based testing Case-Control Study 2 Inclusion Criteria: At least 18 years of age Able and willing to provide informed consent Resident in the cluster during the first round of testing Tested HIV-infected in CHiP home-based testing, or HIV-infected and disclosed that they were previously diagnosed as HIV-infected to CHiP team Case-Control Study 3 Inclusion Criteria: At least 18 years of age Able and willing to provide informed consent Resident in the cluster during the second round of testing Visited by a CHiP team and offered testing during the second round of home-based testing Exclusion Criteria: Population Cohort Exclusion Criteria: Current or planned enrollment in another HIV treatment, prevention, or Pre-Exposure Prophylaxis (PrEP) study Current, planned or prior enrollment in an HIV vaccine study Anything that, in the opinion of the investigator, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives. Case-Control Study 1 Exclusion Criteria: Individuals belonging to the Population Cohort or other case-control studies Individuals known to be HIV-infected after testing elsewhere. Case-Control Study 2 Exclusion Criteria: Individuals enrolled in the Population Cohort or other case-control studies HIV-infected individuals already on ART before study commences Case-Control Study 3 Exclusion Criteria: Known HIV infected from CHiP data. Individuals belonging to the Population Cohort or other case-control studies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 44 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A Universal Testing w/Immediate ART<br> | Other: Universal Testing with immediate ART<br>* • Combination prevention package including: o House-to-house deployment of: Universal HIV counseling and testing; Active linkage to care for individuals diagnosed as HIV-infected, with immediate eligibility for ART; Promotion of male circumcision and prevention of mother to child transmission (PMTCT) services; Provision of condoms; Strengthening of HIV testing and services at health facilities and other venues; Strengthening of male circumcision and prevention of mother-to-child transmission of HIV services available in the community; and Treatment of sexually transmitted infections (STIs) and provision of condoms at health units<br>* Other names: UTT;|
| Active Comparator: Arm B ART according to National Guidelines<br> | Other: Universal Testing with ART eligibility according to National Guidelines<br>* Combination prevention package including: House-to-house deployment of: Universal HIV counseling and testing; Active linkage to care for individuals diagnosed as HIV-infected, with ART eligibility according to national guidelines; Promotion of male circumcision and PMTCT services; Provision of condoms; Strengthening of HIV testing and services at health facilities and other venues; Strengthening of male circumcision and PMTCT services available in the community; and Treatment of STIs and provision of condoms at health units.<br>* Other names: PopART Intervention;|
| Other: Standard of Care<br>Includes: Strengthening of HIV testing and ART services according to national guidelines at health facilities and other venues; Strengthening of male circumcision and PMTCT services available at health facilities and other venues in the community; and Treatment of STIs and provision of condoms at health facilities and other venues in the community. | Other: Standard of Care<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV incidence measured over 3 years in the Population Cohort, with the primary analysis including HIV incidence measured between Months 12 and 36 of the study. |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HIV incidence over the first, second, and third years of follow-up |  | 3 years | 
| ART adherence and viral suppression | HIV viral load at 24 months in HIV-infected members of the Population Cohort who initiated HIV care and ART after commencement of the PopART intervention in the community (if funding available) | 24 months | 
| Herpes Simplex Virus -2 (HSV-2) incidence | Incident HSV-2 infections at 12 months, 24 months, and 36 months for all individuals in the Population Cohort who were HSV-2-uninfected at enrollment | 12 months, 24 months, and 36 months | 
| HIV disease progression, retention in care, and death |  | 3 years | 
| ART toxicity | ART safety and clinical events among Population Cohort participants initiating ART after commencement of the PopART intervention in the community, measured using routine health center data, and ART safety and clinical events among health center attendees who initiated ART after commencement of the PopART intervention in the community, measured using routine health center data | 3 years | 
| Sexual risk behavior | o Self-reported sexual risk behavior at Enrollment, 12 months, 24 months, and 36 months in the Population Cohort | 3 years | 
| Case notification rate of tuberculosis (TB) | Case notification rates of bacteriologically-confirmed TB diagnosed among the general population of patients seeking care at health centers as recorded by health centers TB mortality among TB cases in the community as recorded by health centers | 3 years | 
| HIV-related stigma | Self-reported data on stigma indicators at enrollment, 12 months, 24 months, and 36 months in the Population Cohort Qualitative interviews in selected members of the general population in Arms A, B, and | 3 years | 
| Uptake of PMTCT | Self-reported use of services for PMTCT at Enrollment, 12 months, 24 months, and 36 months among HIV-infected women in the Population Cohort who had been pregnant in the prior 12 months Uptake of PMTCT services at health centers Uptake of PMTCT as indicated in data collected in households by CHiPs | 3 years | 
| Uptake of male circumcision | Self-reported circumcision status/uptake at Enrollment, 12 months, 24 months, and 36 months of men in the Population Cohort Uptake of circumcision in the community as indicated in health center data Uptake of circumcision as indicated in data collected in households by CHiPs | 3 years | 
| ART screening and uptake | The proportion of Population Cohort members, identified as HIV-infected who screen for ART eligibility, and who subsequently initiate ART Proportion of community members, identified as HIV-infected in data from CHiP teams, who screen for ART eligibility, and who subsequently initiate ART, as indicated in health center data | 3 years | 
| HIV testing and retesting | Self-reported recent HIV testing at Enrollment, 12 months, 24 months, and 36 months in the Population Cohort The number of adults (16 years and older) in the household and the number of HIV tests performed as indicated in data from CHiP teams and health centers | 3 years | 
| Time between HIV diagnosis and initiation of care | The proportion of Population Cohort members initiating HIV care within 3 months of a positive HIV diagnosis The proportion of community members initiating HIV care within 3 months of HIV diagnosis as indicated in data from CHiP teams (provision of HIV positive result) and health center data (date of care initiation) | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Universal Test and Treat (UTT), Combination Prevention