An observational study in HIV-1-infection, sponsored by Radboud University Medical Center. Completed at 3 sites in Netherlands. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-11-27.
Sponsored by Radboud University Medical Center · Observational
Some individuals are able to spontaneously control HIV replication, the so-called 'elite controllers' (ECs). ECs are crucial for our understanding of HIV infection. While there is more and more evidence pointing towards a role of the innate immune system in elite control, no research has been performed on the role of innate trained immunity in elite control of HIV.
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.
Rationale:
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:
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.
Radboud University Medical Center is the lead sponsor of 959 studies on the registry; 134 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
Counted across the registry records on this site, refreshed daily.
A recent query of the Dutch national database of HIV (Athena Cohort; Stichting Hiv Monitoring (SHM)) revealed there are approximately 138 HIV elite controllers in the Netherlands, according to the definition used in the 2000HIV study. Of these, 80 HIV elite controllers are expected to participate in the 2000HIV study. Thanks to the query, each one of four 2000HIV participating centers is notified about who the HIV elite controllers in their center are. All HIV elite controllers participating in the 2000HIV will be approached and asked whether they have a first-degree relative who is available and willing to have a single venipuncture.
All participants:
Due to distorting effects on immune parameters and immune responses, participation is either not possible or must be delayed in case of the following:
HIV elite controllers:
HIV elite controllers in the 2000HIV that have an available first-degree relative. Definition of HIV elite controller is the same as in the 2000HIV, see definition on page 7 of the protocol and in the group description.
ART-suppressed people living with HIV:
As a control group, ART-suppressed people living with HIV in the 2000HIV that have an available first-degree relative will be included.
ART-suppressed people living with HIV need to apply to the following criteria to participate in the 2000HIV: ≥18 years, on cART ≥6 months with an HIV-RNA load \<200 copies/mL.
For this 2000HIV-trained study, additional criteria for ART-suppressed people living with HIV are:
Eligible ART-suppressed people living with HIV will be matched by sex and age (max. 5-10 years apart), where possible. Similarity in family members between groups will also be pursued. That is why the HIV elite controllers and their family members will be enrolled first. Thereafter, the ART suppressed people living with HIV and their family members will be recruited and enrolled.
First-degree relatives:
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.
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
Direct cytokine responses
Isolated monocytes and NK-cells will be stimulated ex vivo with a range of stimuli. Cytokines released in the supernatants will be measured by ELISA.
Time frame: 24 hour ex vivo experiment
Cytokine responses after 6-day training
Isolated monocytes and NK-cells will be trained ex vivo and the innate training effect will be studied after restimulation with an unrelated stimulus on day 7. Cytokines released in the supernatant and intracellularly will be measured by ELISA.
Time frame: 7 day ex vivo experiment
Transcriptome
RNA in the cells will be analysed to gain a transcriptional signature.
Time frame: 1 year after sample collection
Epigenome
Epigenetic signatures will be studied by means of ChIP sequencing and ATAC sequencing.
Time frame: 1 year after sample collection
Immune phenotyping
Circulating cells are phenotyped by menas of elaborate flow cytometry panels.
Time frame: 1 year after sample collection
Vaccination history
All groups
Time frame: Collected during visit
History of contracting COVID19
All groups
Time frame: Collected during visit
Age
Only in first-degree relatives. Information on HIV patients already available from 2000HIV study (NCTNCT03994835).
Time frame: Collected during visit
Biological sex
Only in first-degree relatives. Information on HIV patients already available from 2000HIV study (NCTNCT03994835).
Time frame: Collected during visit
Medical history
Only in first-degree relatives. Information on HIV patients already available from 2000HIV study (NCTNCT03994835).
Time frame: Collected during visit
Medication use
Only in first-degree relatives. Information on HIV patients already available from 2000HIV study (NCTNCT03994835).
Time frame: Collected during visit
Plan to share: Undecided
No publications or documents are linked to this record.
This study is completed, as verified in Nov 2023. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Radboud University Medical Center