2000HIV Trained Innate Immunity in HIV Elite Controllers

NCT04968717 | Completed

• 2 other identifiers: NL76999.091.212021-7495
• Study Type: observational
• Target: 109
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  7 day ex vivo experiment

• Transcriptome

  RNA in the cells will be analysed to gain a transcriptional signature.

  1 year after sample collection

• Epigenome

  Epigenetic signatures will be studied by means of ChIP sequencing and ATAC sequencing.

  1 year after sample collection

• Immune phenotyping

  Circulating cells are phenotyped by menas of elaborate flow cytometry panels.

  1 year after sample collection

Other Outcomes (6)

• Vaccination history

  Collected during visit

• History of contracting COVID19

  Collected during visit

• Age

  Collected during visit

Study Arms (4)

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

First-degree relatives of HIV elite controllers

cART-treated non-controller HIV patients

First-degree relatives of cART-treated non-controller HIV patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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: * All participants must be ≥18 years of age. * Due to distorting effects on immune parameters and immune responses, participation is either not possible or must be delayed in case of the following: * active hepatitis B/C or signs of acute infections * active or recent malignant condition (i.e. \<12 months ago treated) * active systemic auto-immune or auto-inflammatory conditions (such as rheumatoid arthritis, inflammatory bowel disease). * use of immunosuppressive medication * pregnant 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: * Never applied to controller definition. * At least one documented HIV RNA load \>100.000 copies/mL * No documentation of recent HIV acquisition combined with ART initiation in less than 6 months. 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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Erasmus Medical Center: collaborator
• Onze Lieve Vrouwe Gasthuis: collaborator
• Elisabeth-TweeSteden Ziekenhuis: collaborator

Study Sites (3)

OLVG

Amsterdam, Netherlands

Location

Radboudumc

Nijmegen, 6525GA, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

Biospecimen

Retention: SAMPLES WITH DNA

* Supernatants after PBMC stimulation experiments (no DNA) for assessment of cytokine production * Plasma for analysis of metabolomics and targeted proteomics (no DNA) * Cells for transcriptome analysis (contains DNA) * Cells prepared for epigenetic analyses (contains DNA) * DNA isolated for GWAS study (only in first-degree relative groups, contains DNA)

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2021
• First Posted: July 20, 2021
• Study Start: August 2, 2021
• Primary Completion: October 27, 2021
• Study Completion: October 27, 2021
• Last Updated: November 27, 2023

Record last verified: 2023-11

Locations

NL (3)