HIV-1-infectionHIV-PRADANCT03426189
HIV Persistence in Lymph Node and Peripheral Blood
An observational study of HIV-1-infection, run by University of Melbourne at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1-infection
- What is being tested?
- Leukapheresis and Lymph node biopsy
- Type of treatment
- Surgery or procedure
- How many people
- 8 participants
- Where
- 1 siteAustralia
- Study dates
- 2 Jan 2017to 17 Oct 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: HIV-infected individuals on long term antiretroviral therapy
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: HIV Persistence in Lymph Node Tissue and Peripheral Blood: The Role of Immune Checkpoints
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.
Read the 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.
- Conditions
- HIV-1-infection
- Being tested
- Leukapheresis, Lymph node biopsy
- Keywords
- HIV, Latent reservoir, Leukapheresis, Inguinal lymph node biopsy, Immune checkpoint, PD1, CTLA4
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LeukapheresisProcedure or surgery
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.
Lymph node biopsyProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| HIV infected individuals on long term ART | * Leukapheresis
* Lymph node biopsy Receives: Procedure: Leukapheresis; Procedure: Lymph node biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of HIV-1 in cells expressing CTLA4 and PD-1 in lymph node derived cells
Measured: Baseline only
Secondary outcomes (2)
Frequency of HIV-1 in cells expressing CTLA4 and PD-1 in blood derived cells
Measured: Baseline only
Change in interferon gamma production in HIV specific T-cells following ex vivo blockade of PD-1 and CTLA4
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
Measured: Baseline only
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2018
- Study start2 Jan 2017
- Primary completion17 Oct 2018
- Study completion17 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Melbourne
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Principal investigator, Sharon Lewin, University of Melbourne
- Investigators
- Sharon Lewin, Principal investigator, The Peter Doherty Institute for Infection and Immunity, University of Melbourne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03426189
- Sponsor's protocol ID
- 1646930
- Acronym
- HIV-PRADA
- Status last verified
- Jun 2021
- First submitted
- 3 Dec 2017
- Last updated
- 23 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HIV Persistence in Lymph Node Tissue and Peripheral Blood: The Role of Immune Checkpoints
- ClinicalTrials.gov ID
- NCT03426189
- Acronym / sponsor ID
- HIV-PRADA / 1646930
- Conditions
- HIV-1-infection
- Keywords
- HIV, Latent reservoir, Leukapheresis, Inguinal lymph node biopsy, Immune checkpoint, PD1, CTLA4
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of MelbourneUniversity, hospital or other
- 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
- Study start
- 2 Jan 2017 (actual)
- Primary completion
- 17 Oct 2018 (actual)
- Study completion
- 17 Oct 2018 (actual)
- First posted
- 8 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HIV infected individuals on long term ART | – | Procedure: Leukapheresis, Procedure: Lymph node biopsy* Leukapheresis * Lymph node biopsy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- HIV-infected individuals on long term antiretroviral therapy
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LeukapheresisBlood 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 or surgery | HIV infected individuals on long term ART |
| Lymph node biopsyUltrasound 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. | Procedure or surgery | HIV infected individuals on long term ART |
Primary outcome
Frequency of HIV-1 in cells expressing CTLA4 and PD-1 in lymph node derived cells
Time frame: Baseline only
2 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sharon Lewin principal investigator
The Peter Doherty Institute for Infection and Immunity, University of Melbourne
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV-1-infection, run by University of Melbourne at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of HIV-1 in cells expressing CTLA4 and PD-1 in lymph node derived cells (time frame: Baseline only). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2021.