2000HIV Trained Innate Immunity in HIV Elite Controllers
NCT ID: NCT04968717
Last Updated: 2023-11-27
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
109 participants
OBSERVATIONAL
2021-08-02
2021-10-27
Brief Summary
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In this cross-sectional case-control study, we will study this role of trained immunity in HIV elite control by comparing ECs both to a non-HIV-infected first-degree relative, and to HIV patients who are not elite controllers. In addition, we will study whether HIV itself can induce a trained innate immunity phenotype.
Detailed Description
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It remains unknown how some individuals spontaneously control HIV in the absence of antiretroviral medication, called HIV 'elite controllers' (ECs). ECs have been absolutely crucial to our current understanding of control of HIV replication. While research has mainly focused on the adaptive immune system, there is a vast amount of evidence indicating that the innate immune system is essential to HIV elite control.
Trained innate immunity can be expressed in terms of enhanced responsiveness of innate immune cells to a repeated trigger. This occurs through epigenetic remodeling after exposure to certain stimuli, such as beta-glucan, lipopolysaccharide (LPS) or the bacillus Calmette-Guérin (BCG) vaccine. Innate training results in an altered gene expression and metabolic reqiring on a cellular level, resulting in greater resistance against subsequent infection.
Both the impact of trained immunity on HIV infections and vice versa, the impact of HIV on trained immunity, are unknown. Our hypothesis is that ECs are natural hyper-responders to innate immune training triggers and that this aids in the HIV elite control phenotype.
Objectives:
1. (Primary) Investigate if a trained immunity profile in innate immune cells plays a role in HIV elite control.
2. (Secondary) Determine the immune phenotypes that distinguish family members of HIV elite controllers from family members of people living with HIV who have never been controllers.
3. (Secondary) Determine whether HIV can induce a long-term functional and transcriptional program in innate immune cells similar to trained immunity.
Study design:
Cross-sectional case-control study.
For the primary objective, HIV elite controllers will be compared to ART-suppressed HIV patients who never have been elite controllers and first-degree relatives of HIV elite controllers will be compared to first-degree relatives of ART-suppressed HIV patients who have never been elite controllers.
For the secondary objectives, first, a system biology approach will be used in the comparison above. To determine the role of HIV in trained innate immunity we will compare people living with HIV (both controllers as non-controllers) to their respective family members.
Conditions
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Study Design
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CASE_CONTROL
CROSS_SECTIONAL
Study Groups
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HIV elite controllers
Non-viremic elite controller:
HIV-positive , \> 1 year without cART AND with \>3 consecutive HIV-RNA \< 75 copies/ml spanning \>12 months AND stable CD4\> 500 cells/uL.(i.e. \>75% of measurements)
OR on cART, but before start cART \> 1 year without cART AND with \>3 consecutive HIV-RNA \< 75 copies/ml spanning \>12 months AND stable CD4\> 500 cells/uL. (i.e. \>75% of measurements)
Viremic elite controller:
HIV-positive \>5 year without cART AND with always HIV-RNA \>50-10.000 copies/ml AND always CD4\> 500 cells/uL.
OR on cART, but before start cART \>5 year without cART AND with always HIV-RNA \>50-10.000 copies/ml AND always CD4\> 500 cells/uL
No interventions assigned to this group
First-degree relatives of HIV elite controllers
No interventions assigned to this group
cART-treated non-controller HIV patients
No interventions assigned to this group
First-degree relatives of cART-treated non-controller HIV patients
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
Aside from the criteria for all participants mentioned above, there are no additional criteria for first-degree relatives of participants with HIV. If multiple first-degree relatives are available, siblings are preferred. If no sibling is available, then children \>18 years. If no children \>18 years, then parents. If there is still multiple options, same-sex will be preferred over different-sex relatives.
18 Years
ALL
Yes
Sponsors
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Erasmus Medical Center
OTHER
Onze Lieve Vrouwe Gasthuis
OTHER
Elisabeth-TweeSteden Ziekenhuis
OTHER
Radboud University Medical Center
OTHER
Responsible Party
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Locations
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OLVG
Amsterdam, , Netherlands
Radboudumc
Nijmegen, , Netherlands
Erasmus MC
Rotterdam, , Netherlands
Countries
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Other Identifiers
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2021-7495
Identifier Type: OTHER
Identifier Source: secondary_id
NL76999.091.21
Identifier Type: -
Identifier Source: org_study_id