SCOPE Analytic Treatment Interruption Protocol

Study Overview
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Brief Summary
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The goal of this study is to understand the interaction between HIV and the host at the earliest stages when HIV medications are paused. Volunteers with HIV will interrupt antiretroviral therapy (ART) and then have intensive studies preformed two to three times per week. Most will resume therapy within three weeks, even if the virus does not rebound during this time.

Detailed Description
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In this study, people living with HIV will undergo intensive sampling prior to and following an interruption of their antiretroviral therapy (ART). Individuals will be asked to resume ART once the virus is detectable, or after approximately three weeks if the virus remains undetectable. Individuals who were able to control their virus before ART (controllers) will be able to participate in an extended treatment interruption and have less restrictive ART restart criteria. The overall goal of the study is to characterize the interaction between the host and the virus at the earliest stages of virus replication and to identify predictors of rebound before virus becomes detectable.

Official Title
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Analytic Treatment Interruption in HIV Infection

Conditions
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HIV/AIDS

Intervention / Treatment
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* Other: Treatment Interruption Arm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent Age >= 18 Documented HIV infection Antiretroviral therapy for at least 12 months Screening plasma HIV RNA levels below level of detection (< 40-75 copies/mL), and all available determinations in past 12 months also below level of detection (blips allowed) Screening CD4+ T-cell count >350 cells/uL If of childbearing potential, willing to use two methods of contraception Willing to receive counseling regarding HIV transmission risk mitigation Exclusion Criteria: Pregnant or plans to become pregnant during the course of the study Active hepatitis B, defined as (1) positive sAg or (2) positive cAb with negative sAb and positive HBV DNA Active hepatitis C, defined as positive Hep C Ab with positive HCV RNA Use of a non-nucleoside reverse transcriptase inhibitor and unable to switch regimen Significant cardiovascular or cerebrovascular disease Recent or prior (within past 5 years) malignancy Severe kidney disease (CrCl < 50 mL/min via Cockroft-Gault method) Severe hepatic impairment (Child-Pugh Class C) or unstable liver disease Concurrent treatment with immunomodulatory drugs Unable or unwilling to use barrier protection or pre-exposure prophylaxis (PrEP) to prevent HIV transmission with sexual partners not known to be HIV-infected

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Interruption Arm<br> | Other: Treatment Interruption Arm<br>* Individuals with HIV on suppressive ART will interrupt their ART.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute retroviral syndrome | The proportion of participants developing acute retroviral syndrome | Week 0 through Month 6 | 
| Failure to re-suppress | The proportion of participants who fail to re-suppress to plasma HIV RNA levels <50 copies/mL after re-initiating ART | Week 0 through Month 12 | 
| CD4+ T cell decline | The proportion of participants with confirmed decreases in CD4+ T cell count below 350 cells/uL | Week 0 through Month 6 | 
| Time to rebound | The time between the treatment interruption and plasma HIV RNA >200 copies/mL | Week 0 through Month 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, HIV/AIDS, Antiretroviral therapy, HIV reservoir, Biomarkers