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2000 HIV Human Functional Genomics Partnership Program (2000HIV)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03994835
Recruitment Status : Active, not recruiting
First Posted : June 21, 2019
Last Update Posted : November 9, 2021
Sponsor:
Collaborators:
ViiV Healthcare
Elisabeth-TweeSteden Ziekenhuis
Erasmus Medical Center
Onze Lieve Vrouwe Gasthuis
Information provided by (Responsible Party):
Radboud University Medical Center

Brief Summary:

Background Chronic HIV infection leads to a dysregulated immune system, even when full viral suppression is achieved. HIV causes persistent immune activation, relating to an array of common non-AIDS-related diseases such as cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). On the other hand, accelerated ageing of the immune system hinders effective immunity against infectious diseases and cancer. Likewise, this derailed inflammatory balance creates a niche for persistent viral replication and reservoir, and prevents cure or functional cure. Mechanisms behind this phenomenon are poorly understood. Inclusion of a larger cohort of HIV-infected patients allows for a more precise assessment of the factors underlying the immune dysregulation.

Primary Objectives

  • Identify a set of candidate biomarkers that correlate with particular non-AIDS-related comorbidities
  • Unravel biological processes associated with extreme HIV clinical phenotypes.
  • Find therapeutic targets to identify novel assets or for repurposing of clinical phase assets from other disease areas for HIV.

Secondary Objectives

  • Evaluate potential relationship of host/immune profiles on efficacy, safety, and tolerability of standard care regimens.
  • Evaluate the contribution of age, sex, and genetics in host-immune profiles that are:

    • distinct to HIV infection relative to controls in other cohorts;
    • associated with non-AIDS-related comorbidities in HIV infection relative to non-HIV chronic disease.

Study design 2000 HIV patients will be included in the cohort. The investigators estimate a 2-year inclusion and 2-year follow-up period and will strive for the inclusion of several clinical phenotypes and classical risk group patients. Patients will be recruited from four Dutch HIV treatment centers.

At inclusion

  1. Collection of metadata using questionnaires and patient medical records
  2. Asses co-pathology (CVD and NAFLD)
  3. Blood will be drawn for genetic, epigenetic, proteomic, metabolomic, microbiome, immunological, and virological analyses

After 2 years follow-up

  1. Collection of metadata using questionnaires and patient medical records
  2. Asses co-pathology (CVD and NAFLD)
  3. Blood samples will be collected for biomarker and infection/inflammation parameter analysis

Condition or disease
HIV Infections

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Study Type : Observational [Patient Registry]
Actual Enrollment : 1909 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 2 Years
Official Title: 2000 HIV Human Functional Genomics Partnership Program
Actual Study Start Date : October 16, 2019
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS




Primary Outcome Measures :
  1. Change in liver fibrosis [ Time Frame: Change: 2-year value - baseline value ]
    Change in liver fibrosis measurement by FibroScan (method by Echosens)

  2. Change in liver steatosis [ Time Frame: Change: 2-year value - baseline value ]
    Change in liver steatosis measurement by FibroScan (method by Echosens) and liver ultrasound (method developed by Radboudumc)

  3. Change in cardiovascular risk score (Framingham score) [ Time Frame: Change: 2-year value - baseline value ]
    Framingham score

  4. Change in cardiovascular risk score (D:A:D score) [ Time Frame: Change: 2-year value - baseline value ]
    D:A:D score

  5. Number and type of cardiovascular events [ Time Frame: Number of events over 2 years between baseline and 2-year time point ]

    Recoring of cadiovascular diseases from patient file:

    • Stroke/ TIA
    • Angina pectoris
    • Myocardial infarction
    • Claudicatio intermittens
    • Venous thrombo-embolism
    • Other …

  6. Genetic data [ Time Frame: At baseline only ]
    Genome-wide genotype data including >8 million SNPs per individual

  7. Colonizing microbiome profile [ Time Frame: At baseline only ]
    Colonizing microbiome profile will be generated from stool and saliva samples

  8. Transcriptomics [ Time Frame: At baseline only ]
    RNA-sequencing will be performed in PBMCs

  9. Quantification of a wide range of metabolites [ Time Frame: At baseline only ]
    Metabolomics analysis by multiplex immunoassays will be performed in plasma or serum

  10. Cytokine production of PBMCs in ex vivo stimulation experiments [ Time Frame: At baseline only ]
    Ex vivo cytokine responses of isolated PBMCs to a range of stimuli (TLR ligands, killed pathogens and viral antigen stimuli)

  11. Immune phenotyping [ Time Frame: At baseline only ]
    Extensive phenotyping of circulating immune cells by flow cytometry analysis

  12. Change in ECG [ Time Frame: ECG paramater changes between baseline and 2-year time visit ]
    Standardized signs of myocardial infarction with MEANS ECG software, as extensively described elsewehere. In addition, we will look at the full list of ECG output measurements as described elsewhere*: in brief, MEANS reliably provides output on interpretation of the ECG rhythm and morphology. The morphological interpretation consists of separate analyses of the P wave, QRS complex, and ST-T segment. Reference: Van den Berg ME, Rijnbeek PR, Niemeijer MN, et al. Normal values of corrected heart-rate variability in 10-second electrocardiograms for all ages. Front Physiol. 2018;9:424

  13. Intima-media thickness [ Time Frame: At baseline only ]
    Ultrasound measurement of intima-media thickness in the carotid artery as a measure for atherosclerosis and cardiovasculr disease risk.


Biospecimen Retention:   Samples With DNA
Blood for DNA isolation (no sequencing, only SNP array) Stool for microbiome analysis Saliva for microbiome analysis Plasma and serum for metabolomics Urine for creatinine analysis


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
HIV-infected patients (n=2000) will be recruited from the following Dutch HIV Treatment Centres: Radboudumc (Nijmegen), ErasmusMC (Rotterdam), Onze Lieve Vrouwe Gasthuis (Amsterdam), Elisabeth-TweeSteden Ziekenhuis (Tilburg). Our aim is to include approximately 20% females, 20% of Sub-Sahara African origin, elite controllers (~2-3%), immunologic non-responders (~3%), and rapid progressors (~4-5%) The total number of adult HIV patients under care in these treatment centers is 7000, of which 80% is male and 70% is of Caucasian origin. There is wide age distribution among the adult HIV population.
Criteria

Inclusion Criteria:

  • HIV-infected,
  • aged ≥18 years,
  • on cART ≥6 months with an HIV-RNA load <200 copies/mL, *Apart from the above-mentioned subjects, elite controllers that are not on cART, are also eligible.

Exclusion Criteria:

  • No informed consent
  • Insufficient communication because of language or other problems
  • Active hepatitis B/C or signs of acute infections
  • Pregnancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03994835


Locations
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Netherlands
Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands, 1091AC
Radboudumc
Nijmegen, Netherlands, 6525GA
Erasmus MC
Rotterdam, Netherlands, 3015GD
Elisabeth Twee-Steden ziekenhuis
Tilburg, Netherlands, 5042AD
Sponsors and Collaborators
Radboud University Medical Center
ViiV Healthcare
Elisabeth-TweeSteden Ziekenhuis
Erasmus Medical Center
Onze Lieve Vrouwe Gasthuis
Investigators
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Principal Investigator: Quirijn de Mast, Dr. Radboud University Medical Center
Principal Investigator: Annelies Verbon, Prof. Erasmus MC
Principal Investigator: Willem Blok, Dr. Onze Lieve Vrouwe Gasthuis
Principal Investigator: Marvin Berrevoets, Drs. Elisabeth Twee-Steden ziekenhuis
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Responsible Party: Radboud University Medical Center
ClinicalTrials.gov Identifier: NCT03994835    
Other Study ID Numbers: NL.68056.091.18
First Posted: June 21, 2019    Key Record Dates
Last Update Posted: November 9, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Radboud University Medical Center:
HIV
Non-alcoholic fatty liver disease
Cardiovascular disease
Omics data
Inflammation
Additional relevant MeSH terms:
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HIV Infections
Blood-Borne Infections
Communicable Diseases
Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases