Ignite Creation Date:
2025-12-25 @ 4:48 AM
Ignite Modification Date:
2026-03-09 @ 8:33 AM
Study NCT ID:
NCT03225118
Status:
COMPLETED
Last Update Posted:
2020-01-18
First Post:
2017-07-20
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Impact of a Short-Term Analytical Treatment Interruption and Re-Initiation of Antiretroviral Therapy on Immunologic and Virologic Parameters in HIV-Infected Individuals
Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)
Organization:
Study Overview
Official Title:
Comprehensive Evaluation of the Impact of a Short-Term Analytical Treatment Interruption and Re-Initiation of Antiretroviral Therapy on Immunologic and Virologic Parameters in HIV-Infected Individuals
Status:
COMPLETED
Status Verified Date:
2020-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background:
The immune system helps the body fight off disease. Most people infected with HIV cannot control the infection and need daily medicine. Combination antiretroviral therapy (cART) are drugs taken to prevent HIV infection from damaging the immune system. Researchers want to study why some people develop resistance to the drugs or have permanent side effects.
Objective:
To study the impact of a short-term treatment stop on HIV that persists even while taking cART.
Eligibility:
Adults 18-65 years old with HIV who are being treated with cART
Design:
* Participants will first be screened with a physical exam and medical history. They may have a chest x-ray. They will have heart, blood, and urine tests.
* At the baseline visit, participants will repeat the screening tests except the x-ray. They will get counseling about HIV and risk behavior.
* Participants will have leukapheresis. Blood will be removed through a needle in one arm. A machine will separate white blood cells from the rest of the blood. The remainder of the blood will be returned to the body by a different needle.
* Participants will stop their current treatment on day 0. They will visit the clinic each week until they meet the criteria to restart cART. These visits will have the same procedures as the baseline visit.
* Before restarting cART, most participants will have leukapheresis.
* After restart, participants will be seen weekly for 4 weeks and then monthly for about 11 months. Participants will have blood drawn, physical exam, and medical history. They will have leukapheresis 2 more times over 1 year.
The immune system helps the body fight off disease. Most people infected with HIV cannot control the infection and need daily medicine. Combination antiretroviral therapy (cART) are drugs taken to prevent HIV infection from damaging the immune system. Researchers want to study why some people develop resistance to the drugs or have permanent side effects.
Objective:
To study the impact of a short-term treatment stop on HIV that persists even while taking cART.
Eligibility:
Adults 18-65 years old with HIV who are being treated with cART
Design:
* Participants will first be screened with a physical exam and medical history. They may have a chest x-ray. They will have heart, blood, and urine tests.
* At the baseline visit, participants will repeat the screening tests except the x-ray. They will get counseling about HIV and risk behavior.
* Participants will have leukapheresis. Blood will be removed through a needle in one arm. A machine will separate white blood cells from the rest of the blood. The remainder of the blood will be returned to the body by a different needle.
* Participants will stop their current treatment on day 0. They will visit the clinic each week until they meet the criteria to restart cART. These visits will have the same procedures as the baseline visit.
* Before restarting cART, most participants will have leukapheresis.
* After restart, participants will be seen weekly for 4 weeks and then monthly for about 11 months. Participants will have blood drawn, physical exam, and medical history. They will have leukapheresis 2 more times over 1 year.
Detailed Description:
While antiretroviral therapy (ART) has improved the clinical outcome for HIV-infected individuals, persistence of viral reservoirs in the peripheral blood and lymphoid tissues remains a hurdle to the eradication of virus. The vast majority of HIV-infected individuals treated with ART experience plasma viral rebound within weeks of cessation of therapy. Considering that current research regarding treatment has been heavily focused on developing strategies aimed at achieving sustained virologic remission in the absence of ART, it is of crucial importance to investigate the impact of short-term treatment interruption and re-initiation of ART on transcriptional, immunologic, and virologic parameters in HIV-infected individuals. Currently, much of our knowledge regarding the mechanism of viral rebound is based on investigations using structured treatment interruptions in supervised clinical settings dating back to 1999. Subsequent studies, performed primarily in chronically infected patients to minimize treatment exposure and toxicity, revealed poor outcomes in terms of viral rebound, clinical events and mortality 3-11 leading to the abandonment of this genre of investigation. However, various aspects have been identified as potential contributors to the observed negative outcomes including outmoded ART regimens, infrequent post-interruption monitoring, and repeated cycles of prolonged analytical treatment interruption (ATI). While long-term ATI was found to be associated with a decrease in CD4+ T cells, persistent plasma viremia, and an increased risk of opportunistic infections, it is unclear whether short term ATI elicits similar immunologic and virologic consequences in those receiving modern and efficacious ART. Furthermore, the mechanism, kinetics, degree, as well as immunologic and virologic predictors, of plasma viral rebound in patients receiving contemporary antiretroviral drug regimens after cessation of ART have not been explicitly investigated. Nor has the impact of persistent HIV reservoir size been fully correlated to the dynamics of plasma viral rebound in patients receiving modern drug regimens. As we develop clinical trials aimed at therapeutic and curative interventions, an integral component in design will require an ATI phase. Characterizing the corollaries of brief treatment cessation and re-initiation of ART on the dynamics of immunologic parameters and HIV reservoirs will provide valuable information for the design of future trials essential to our interpretation of the results as well as to ensuring the safest environment for the patients. We propose to examine the effect of ATI on plasma viral rebound, changes in immunologic parameters and the dynamics of viral reservoirs in HIV-infected individuals receiving state-of-the-art antiretroviral drug regimens following discontinuation and reinitiation of therapy.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 17-I-0106 | None | None | View |