Primary objective:Investigate if a trained immunity profile in innate immune cells might be a mechanism of HIV elite control.Secondary objectives:1. Determine the immune phenotypes that distinguishes family members of HIV elite controllers from…
ID
Source
Brief title
Condition
- Immune disorders NEC
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study endpoints
1. Innate immune training indices:
o Direct cytokine responses to a range of stimuli
o Cytokine responses after 6-day training with Beta-glucan
Secondary outcome
Secundary study parameters:
1. Transcriptome signatures of innate immune training (including long
non-coding RNA patterns)
2. Epigenetic signatures of innate immune training
3. Differentially expressed genes on a transcriptomic level that are associated
with HIV elite controller phenotype or their family members.
4. Specific populations of circulating cells, identified by immune phenotyping,
that can differentiate between HIV elite controller phenotype and
ART-suppressed people with HIV, or their respective family members.
Background summary
It remains unknown how some individuals spontaneously control HIV in the
absence of antiretroviral medication, called HIV *elite controllers* (ECs).
Since the beginning, ECs have been absolutely crucial to our current
understanding of HIV and they continue to be to this day. While numerous
research focused on the adaptive immune system, there is a vast amount of
evidence prompting 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 a certain stimulus such as beta-glucan,
lipopolysaccharide (LPS) or the bacillus Calmette-Guérin (BCG) vaccine. This
results in an altered expression and metabolism on a cellular level, resulting
in greater resistance against subsequent infection.
Both the impact of trained immunity of HIV infections as vice versa,
specifically the impact of HIV on trained immunity, are unknown. Our hypothesis
is that ECs are natural hyperresponders to innate immune training triggers and
that this results in the HIV elite control phenotype.
Study objective
Primary objective:
Investigate if a trained immunity profile in innate immune cells might be a
mechanism of HIV elite control.
Secondary objectives:
1. Determine the immune phenotypes that distinguishes family members of HIV
elite controllers from family members of people living with HIV who have never
been controllers.
2. Determine whether HIV can induce a long-term functional and transcriptional
program in innate immune cells similar to trained immunity.
Study design
Study design: cross-sectional case-control study.
For the primary objective, HIV elite controllers will be compared to
ART-suppressed HIV patients that 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.
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 with HIV (both controllers as non-controllers) to their
respective family members.
Study burden and risks
Burden: a single venipuncture, a total amount of 100 mL blood will be
collected. There are no risks other than a small chance of a local hematoma
related to a single venous puncture. There will be no direct benefits for the
subjects enrolled in this study.
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Listed location countries
Age
Inclusion criteria
All participants/first degree relatives:
1. All participants must be *18 years of age.
HIV elite controllers:
1. Participation in 2000HIV study
2. Available first-degree relative
3. Meet criteria of elite controller (see protocol page 7 for elaborate
definition)
ART-suppressed people with HIV:
1. On cART *6 months with an HIV-RNA load <200 copies/mL
2. Never applied to controller definition.
3. At least one documented HIV RNA load >100.000 copies/mL
4. No documentation of recent HIV acquisition combined with ART initiation in
less than 6 months
5. Available first-degree relative
Exclusion criteria
All participants:
1. Active hepatitis B/C or signs of acute infections
2. Active or recent malignant condition (i.e. <12 months ago treated)
3. Active systemic auto-immune or auto-inflammatory conditions (such as
rheumatoid arthritis, inflammatory bowel disease).
4. Use of immunosuppressive medication
5. Pregnant
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCTnummervolgtnog |
| CCMO | NL76999.091.21 |