Imaging and Biopsy During Treatment Interruption for HIV/AIDS
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must be taking: Antiretrovirals
Must not be taking: Steroids, Anticonvulsants, Catecholamines
Disqualifiers: Pregnancy, Diabetes, Hepatitis, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial uses special scans and tissue samples to find and study areas in the body where HIV might still be active in adults receiving ongoing HIV treatment.
Will I have to stop taking my current medications?
If you are in the group that stops ART, you will need to stop your antiretroviral therapy for up to 90 days. The protocol does not specify about other medications, but you should discuss with the study team if you are taking drugs that might interfere with the study.
What data supports the effectiveness of the treatment Acute Treatment Interruption, Analytic Treatment Interruption, ATI for HIV/AIDS?
Research shows that stopping HIV treatment temporarily (ATI) does not increase the amount of HIV in the body or cause immune system problems when treatment is restarted. This suggests ATI can be safely used in studies to see if new treatments can control HIV without ongoing medication.
12345Is it safe to participate in a clinical trial involving treatment interruption for HIV/AIDS?
Treatment interruptions in HIV trials, known as analytical treatment interruptions (ATI), can pose risks, including the potential for HIV transmission and discomfort from pausing medication. However, strategies are being developed to minimize these risks and ensure participant safety.
36789How does the treatment interruption for HIV/AIDS differ from other treatments?
This treatment involves temporarily stopping antiretroviral therapy (ART) to assess if the body can control the virus without medication, which is different from continuous ART that is typically used to manage HIV. This approach, known as analytical treatment interruption (ATI), is unique because it helps researchers understand if a sustained virologic remission can be achieved without ongoing medication.
1341011Eligibility Criteria
Adults over 18 with HIV, on ART for at least 3 years with low viral levels, and a CD4 count of >=350 cells/microliter. They must consent to genetic testing and allow future research use of their samples. Participants agree to stop ART for up to 90 days and use barrier contraception or abstain from sex until viral re-suppression post-ART.Inclusion Criteria
Participants must be willing to use a barrier method of contraception or remain abstinent during ATI and after re-initiating ART until viral re-suppression is achieved to prevent pregnancy and transmission of HIV
Participants must have CD4 cell count >=350 cells/microliter
Participants must have established medical care outside NIH
+8 more
Exclusion Criteria
Pregnant participants
I have a history of HIV-related brain issues.
Participants with known history of initiating ART during the first year of HIV infection
+23 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Baseline and Initial Imaging
Participants undergo initial PET/CT imaging and baseline assessments
Up to 45 days
1 visit (in-person)
Analytic Treatment Interruption (ATI)
Participants randomized to ATI will halt ART and undergo weekly monitoring and PET/CT scans
Up to 90 days
Weekly visits (in-person)
Continued ART Monitoring
Participants continuing ART will have follow-up PET/CT scans and biopsies
12-16 weeks
2 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
2 visits (in-person)
Participant Groups
The study is examining the location of HIV-infected cells in individuals on ART by comparing two groups: one continues ART while undergoing PET/CT scans; the other stops ART temporarily for additional scans and frequent blood tests before resuming treatment.
2Treatment groups
Experimental Treatment
Active Control
Group I: ATIExperimental Treatment1 Intervention
Participants randomized to ATI will halt their ART medications starting 2 weeks (more or less 3 days) after the first imaging visit. This plan will be discussed with participants during the baseline visit. Patients will be contacted 1-3 days prior to ATI initiation. ATI may be delayed or cancelled if there are new safety concerns. HIV plasma viral levels and CD4 counts will be monitored every week during the ATI phase. If a participant meets any of the ART restart criteria during the ATI phase, then they will discontinue ATI and restart ART. Participants who do not meet restart criteria will remain off ART and continue to be monitored weekly until they have been on ATI for 90 days, and then will restart ART.
Group II: Continue ARTActive Control1 Intervention
Participants will continue on their pre-study ART throughout the trial.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Impact of Treatment Interruption on HIV Reservoirs and Lymphocyte Subsets in Individuals Who Initiated Antiretroviral Therapy During the Early Phase of Infection. [2020]Therapeutic strategies for achieving sustained virologic remission are being explored in human immunodeficiency virus (HIV)-infected individuals who began antiretroviral therapy (ART) during the early phase of infection. In the evaluation of such therapies, clinical protocols should include analytical treatment interruption (ATI); however, the immunologic and virologic impact of ATI in individuals who initiated ART early has not been fully delineated. We demonstrate that ATI causes neither expansion of HIV reservoirs nor immunologic abnormalities following reinitiation of ART. Our findings support the use of ATI to determine whether sustained virologic remission has been achieved in clinical trials of individuals who initiated ART early during HIV infection.
Analytical Treatment Interruption in HIV Trials: Statistical and Study Design Considerations. [2022]Analytical treatment interruption (ATI) remains an essential component in clinical studies investigating novel agents or combination treatment strategies aiming to induce HIV treatment-free remission or long-term viral control. We provide an overview on key study design aspects of ATI trials from the perspective of statisticians.
Balancing Statistical Power and Risk in HIV Cure Clinical Trial Design. [2022]Analytical treatment interruptions (ATI) are pauses of antiretroviral therapy (ART) in the context of human immunodeficiency virus (HIV) cure trials. They are the gold standard in determining if interventions being tested can achieve sustained virological control in the absence of ART. However, withholding ART comes with risks and discomforts to trial participant. We used mathematical models to explore how ATI study design can be improved to maximize statistical power, while minimizing risks to participants.
Safety and factors predicting the duration of first and second treatment interruptions guided by CD4+ cell counts in patients with chronic HIV infection. [2006]To evaluate the safety of treatment interruption (TI) guided by CD4+ count in HIV-infected patients followed-up prospectively.
Acute HIV-1 infection viremia associate with rebound upon treatment interruption. [2023]Analytic treatment interruption (ATI) studies evaluate strategies to potentially induce remission in people living with HIV-1 but are often limited in sample size. We combined data from four studies that tested three interventions (vorinostat/hydroxychloroquine/maraviroc before ATI, Ad26/MVA vaccination before ATI, and VRC01 antibody infusion during ATI).
Systematic Review and Meta-analysis of Treatment Interruptions in Human Immunodeficiency Virus (HIV) Type 1-infected Patients Receiving Antiretroviral Therapy: Implications for Future HIV Cure Trials. [2021]Safety and tolerability of analytical treatment interruptions (ATIs) as a vital part of human immunodeficiency virus type 1 (HIV-1) cure studies are discussed. We analyzed current evidence for the occurrence of adverse events (AEs) during TIs.
A collaborative, multidisciplinary approach to HIV transmission risk mitigation during analytic treatment interruption. [2021]Analytic treatment interruptions (ATIs) are currently the standard for assessing the impact of experimental interventions aimed at inducing sustained antiretroviral therapy (ART)-free remission in trials related to HIV cure. ATIs are associated with substantial risk to both study participants and their sexual partner(s). Two documented HIV transmissions occurring in the context of ATIs have been recently reported, but recommendations for mitigating the risk of such events during ATIs are limited. We outline a practical approach to risk mitigation during ATI studies and describe strategies we are utilising in an upcoming clinical trial that may be applicable to other centres.
Recommendations for analytical antiretroviral treatment interruptions in HIV research trials-report of a consensus meeting. [2023]Analytical antiretroviral treatment interruption (ATI) is an important feature of HIV research, seeking to achieve sustained viral suppression in the absence of antiretroviral therapy (ART) when the goal is to measure effects of novel therapeutic interventions on time to viral load rebound or altered viral setpoint. Trials with ATIs also intend to determine host, virological, and immunological markers that are predictive of sustained viral control off ART. Although ATI is increasingly incorporated into proof-of-concept trials, no consensus has been reached on strategies to maximise its utility and minimise its risks. In addition, differences in ATI trial designs hinder the ability to compare efficacy and safety of interventions across trials. Therefore, we held a meeting of stakeholders from many interest groups, including scientists, clinicians, ethicists, social scientists, regulators, people living with HIV, and advocacy groups, to discuss the main challenges concerning ATI studies and to formulate recommendations with an emphasis on strategies for risk mitigation and monitoring, ART resumption criteria, and ethical considerations. In this Review, we present the major points of discussion and consensus views achieved with the goal of informing the conduct of ATIs to maximise the knowledge gained and minimise the risk to participants in clinical HIV research.
Acceptability, motivation and the prospect of cure for people living with HIV and their healthcare providers in HIV cure-focused treatment interruption studies. [2021]Analytical treatment interruptions (ATI) are commonly used clinical endpoints to assess interventions aimed at curing HIV or achieving antiretroviral therapy (ART)-free HIV remission. Understanding the acceptability of ATI amongst people living with HIV (PLHIV) and their HIV healthcare providers (HHP) is limited.
CD4+ cell-count-guided treatment interruptions in chronic HIV-infected patients with good response to highly active antiretroviral therapy. [2019]To evaluate the safety of treatment interruption guided by CD4+ cell count in HIV-infected patients followed up prospectively.
Analytical antiretroviral therapy interruption does not irreversibly change preinterruption levels of cellular HIV. [2020]The impact of short-term analytical treatment interruptions (ATI) on the levels of cellular HIV and of residual activation after subsequent antiretroviral therapy (ART)-mediated plasma HIV viral load re-suppression remains under active investigation.