2000 HIV Human Functional Genomics Partnership Program

NCT03994835 | Completed DMC

• 1 other identifier: NL.68056.091.18
• Study Type: observational
• Target: 1,910
• Locations: 1 country
• Sites: 4

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
• Collection of metadata using questionnaires and patient medical records
• Asses co-pathology (CVD and NAFLD)
• Blood will be drawn for genetic, epigenetic, proteomic, metabolomic, microbiome, immunological, and virological analyses
• Collection of metadata using questionnaires and patient medical records
• Asses co-pathology (CVD and NAFLD)
• Blood samples will be collected for biomarker and infection/inflammation parameter analysis

Conditions

HIV Infections

Keywords

HIV; Non-alcoholic fatty liver disease; Cardiovascular disease; Omics data; Inflammation

Outcome Measures

Primary Outcomes (13)

• Change in liver fibrosis

  Change in liver fibrosis measurement by FibroScan (method by Echosens)

  Change: 2-year value - baseline value

• Change in liver steatosis

  Change in liver steatosis measurement by FibroScan (method by Echosens) and liver ultrasound (method developed by Radboudumc)

  Change: 2-year value - baseline value

• Change in cardiovascular risk score (Framingham score)

  Framingham score

  Change: 2-year value - baseline value

• Change in cardiovascular risk score (D:A:D score)

  D:A:D score

  Change: 2-year value - baseline value

• Number and type of cardiovascular events

  Recoring of cadiovascular diseases from patient file: * Stroke/ TIA * Angina pectoris * Myocardial infarction * Claudicatio intermittens * Venous thrombo-embolism * Other …

  Number of events over 2 years between baseline and 2-year time point

• Genetic data

  Genome-wide genotype data including \>8 million SNPs per individual

  At baseline only

• Colonizing microbiome profile

  Colonizing microbiome profile will be generated from stool and saliva samples

  At baseline only

• Transcriptomics

  RNA-sequencing will be performed in PBMCs

  At baseline only

• Quantification of a wide range of metabolites

  Metabolomics analysis by multiplex immunoassays will be performed in plasma or serum

  At baseline only

• Cytokine production of PBMCs in ex vivo stimulation experiments

  Ex vivo cytokine responses of isolated PBMCs to a range of stimuli (TLR ligands, killed pathogens and viral antigen stimuli)

  At baseline only

• Immune phenotyping

  Extensive phenotyping of circulating immune cells by flow cytometry analysis

  At baseline only

• Change in ECG

  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

  ECG paramater changes between baseline and 2-year time visit

• Intima-media thickness

  Ultrasound measurement of intima-media thickness in the carotid artery as a measure for atherosclerosis and cardiovasculr disease risk.

  At baseline only

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (4)

Onze Lieve Vrouwe Gasthuis

Amsterdam, 1091AC, Netherlands

Location

Radboudumc

Nijmegen, 6525GA, Netherlands

Location

Erasmus MC

Rotterdam, 3015GD, Netherlands

Location

Elisabeth Twee-Steden ziekenhuis

Tilburg, 5042AD, Netherlands

Location

Related Publications (3)

• Blaauw MJT, Navas A, Vasquez VR, Vadaq N, Berrevoets MAH, Otten T, Vos WAJW, van Eekeren LE, Groenendijk AL, Weijers G, Lutgens E, Koenen HJPM, de Jonge MI, Netea MG, Rutten JHW, van der Ven AJAM, Riksen NP. Functional and transcriptional senescence profiles of CD8+ T cells associate with the presence of carotid plaques in people living with HIV. J Infect Dis. 2026 Jan 7:jiag018. doi: 10.1093/infdis/jiag018. Online ahead of print.

  PMID: 41498526 DERIVED

• Blaauw MJT, Berrevoets MAH, Vos WAJW, Groenendijk AL, van Eekeren LE, Vadaq N, Weijers G, van der Ven AJAM, Rutten JHW, Riksen NP. Traditional Cardiovascular Risk Factors Are Stronger Related to Carotid Intima-Media Thickness Than to Presence of Carotid Plaques in People Living With HIV. J Am Heart Assoc. 2023 Oct 17;12(20):e030606. doi: 10.1161/JAHA.123.030606. Epub 2023 Oct 7.

  PMID: 37804189 DERIVED

• Vadaq N, Zhang Y, Vos WA, Groenendijk AL, Blaauw MJ, van Eekeren LE, Jacobs-Cleophas M, van de Wijer L, Dos Santos JC, Gasem MH, Joosten LA, Netea MG, de Mast Q, Fu J, van der Ven AJ, Matzaraki V. High-throughput proteomic analysis reveals systemic dysregulation in virally suppressed people living with HIV. JCI Insight. 2023 Jun 8;8(11):e166166. doi: 10.1172/jci.insight.166166.

  PMID: 37079385 DERIVED

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

MeSH Terms

Conditions

HIV Infections; Non-alcoholic Fatty Liver Disease; Cardiovascular Diseases; Inflammation

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Quirijn de Mast, Dr.

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Annelies Verbon, Prof.

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

• Willem Blok, Dr.

  Onze Lieve Vrouwe Gasthuis

  PRINCIPAL INVESTIGATOR

• Marvin Berrevoets, Drs.

  Elisabeth Twee-Steden ziekenhuis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2019
• First Posted: June 21, 2019
• Study Start: October 16, 2019
• Primary Completion: July 27, 2023
• Study Completion: July 28, 2023
• Last Updated: December 8, 2023

Record last verified: 2023-11

Locations

NL (4)