HIV Persistence in Lymph Node and Peripheral Blood (HIV-PRADA)
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|ClinicalTrials.gov Identifier: NCT03426189|
Recruitment Status : Active, not recruiting
First Posted : February 8, 2018
Last Update Posted : April 9, 2020
|Condition or disease||Intervention/treatment|
|HIV-1-infection||Procedure: Leukapheresis Procedure: Lymph node biopsy|
Combination antiretroviral therapy (ART) has significantly improved the immune function of HIV infected individuals and has transformed a fatal disease into a chronic infection for those with access to ART. Despite suppressing HIV-1 replication, ART is not curative and nearly all HIV infected individuals experience viral rebound within weeks or months of discontinuing ART. This rebound is because HIV is able to hide in long-lived and proliferating CD4+ T cells, a specific type of cell, found in the immune system. The ability to hide is referred to as HIV latency.
One strategy towards eliminating the reservoir of latently infected cells is characterized by the use of latency reversing agents (LRA) to reverse HIV-1 latency. This exposes virus-expressing cells to the immune system and ART virus-mediated cell lysis or immune-mediated killing. Emerging data suggests that HIV-1 is enriched in cells expressing certain proteins known as immune checkpoints (IC). Immune checkpoint proteins play an important role in the regulation of the immune system. By blocking the immune checkpoint with drugs, this approach would allow the immune system to recognize HIV infected cells as foreign and thereby attack and kill the cell. Currently, there are licensed antibodies to the specific IC known as PD-1 (Programmed cell death protein 1) and CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4). These antibodies are in clinical use for the treatment of a range of malignancies.
Most of what is known about HIV-1 latency, reservoir composition, activation of HIV-1 by LRAs and viral enrichment in cells expressing IC in individuals on suppressive ART, is based on studies of peripheral blood T cells rather than lymphoid tissue. However, only 10% of the body's total CD4+T cell population is circulating at any one time. The rest of the CD4+ T cell population resides in the lymph nodes. In addition, cells that express IC are usually located in lymph nodes.
Using CD4+ T-cells from blood and lymph node tissue collected from HIV-infected individuals on ART, this study will examine if HIV is located in cell populations that express ICs and if blocking IC pathways can boost immune recognition of HIV infected cells.
|Study Type :||Observational|
|Actual Enrollment :||8 participants|
|Official Title:||HIV Persistence in Lymph Node Tissue and Peripheral Blood: The Role of Immune Checkpoints|
|Actual Study Start Date :||January 2, 2017|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||January 2021|
HIV infected individuals on long term ART
Blood will be taken by a needle inserted into a vein in one arm and processed through a machine, which spins the blood so that the white blood cells will be separated out of the machine for purposes of this research. The rest of the blood will be returned through a needle in the other arm.
Procedure: Lymph node biopsy
Ultrasound will be used to localize the position of one lymph node in the groin. Under a light general anesthetic, one lymph node will be removed.
- Frequency of HIV-1 in cells expressing CTLA4 and PD-1 in lymph node derived cells [ Time Frame: Baseline only ]
- Frequency of HIV-1 in cells expressing CTLA4 and PD-1 in blood derived cells [ Time Frame: Baseline only ]
- Change in interferon gamma production in HIV specific T-cells following ex vivo blockade of PD-1 and CTLA4 [ Time Frame: Baseline only ]Using blood and tissue from HIV infected individuals on ART, intracellular cytokine staining will be performed to detect interferon and other cytokines following stimulation with HIV pooled peptides
Biospecimen Retention: Samples With DNA
- Blood (CD4+ T cells, CD8+ T cells; plasma)
- Lymph node biopsy (CD4+ T cells, CD8+ T cells)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03426189
|Melbourne, Victoria, Australia, 3181|
|Principal Investigator:||Sharon Lewin||The Peter Doherty Institute for Infection and Immunity, University of Melbourne|