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HIV Persistence in Lymph Node and Peripheral Blood (HIV-PRADA)

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ClinicalTrials.gov Identifier: NCT03426189
Recruitment Status : Recruiting
First Posted : February 8, 2018
Last Update Posted : February 8, 2018
Sponsor:
Collaborators:
amfAR, The Foundation for AIDS Research
University of California, San Francisco
Monash University
Université de Montréal
The Avenue Hospital
Oregon Health and Science University
Johns Hopkins University
Information provided by (Responsible Party):
Sharon Lewin, University of Melbourne

Brief Summary:
The aim of this project is to determine whether latent HIV is enriched in cells expressing certain proteins (receptors) on their surface and whether it is possible to eliminate these cells through the use of drugs that specifically target these proteins. Lymph nodes are known to contain very high numbers of HIV infected cells.

Condition or disease Intervention/treatment
HIV-1-infection Procedure: Leukapheresis Procedure: Lymph node biopsy

Detailed Description:

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
Estimated Enrollment : 20 participants
Observational Model: Cohort
Time Perspective: Prospective
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 2018
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Group/Cohort Intervention/treatment
HIV infected individuals on long term ART
  • Leukapheresis
  • Lymph node biopsy
Procedure: Leukapheresis
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.



Primary Outcome Measures :
  1. Frequency of HIV-1 in cells expressing CTLA4 and PD-1 in lymph node derived cells [ Time Frame: Baseline only ]

Secondary Outcome Measures :
  1. Frequency of HIV-1 in cells expressing CTLA4 and PD-1 in blood derived cells [ Time Frame: Baseline only ]
  2. 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)


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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
HIV-infected individuals on long term antiretroviral therapy
Criteria

Inclusion Criteria:

  • Written Informed Consent
  • Willing to undergo leukapheresis and lymph node biopsy
  • Documented HIV-1 infection (antibody positive or detectable plasma HIV-1 RNA)
  • Receiving combination ART
  • HIV RNA < 50 copies/mL for > 3 years (Episodes of a single HIV plasma RNA 50-500 copies/mL will not exclude participation if the subsequent HIV plasma RNA was <50 copies/mL)

Exclusion Criteria:

  • Unwillingness to follow protocol requirements
  • Contraindications to LN biopsy or leukapheresis
  • Current skin infection of inguinal area
  • Known current lower extremity, gastrointestinal or genitourinary infection

Information from the National Library of Medicine

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


Contacts
Contact: Barbara Scher, BSc(Hons)MSc +61 3 8344 077 barbara.scher@unimelb.edu.au

Locations
Australia, Victoria
Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3181
Contact: Study Nurse    +61 3 9076 6908    clinresearch@alfred.org.au   
Sponsors and Collaborators
University of Melbourne
amfAR, The Foundation for AIDS Research
University of California, San Francisco
Monash University
Université de Montréal
The Avenue Hospital
Oregon Health and Science University
Johns Hopkins University
Investigators
Principal Investigator: Sharon Lewin The Peter Doherty Institute for Infection and Immunity, University of Melbourne

Responsible Party: Sharon Lewin, Director, The Peter Doherty Institute for Infection and Immunity, University of Melbourne
ClinicalTrials.gov Identifier: NCT03426189     History of Changes
Other Study ID Numbers: 1646930
First Posted: February 8, 2018    Key Record Dates
Last Update Posted: February 8, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sharon Lewin, University of Melbourne:
HIV
Latent reservoir
Leukapheresis
Inguinal lymph node biopsy
Immune checkpoint
PD1
CTLA4