Sequential Analysis Before and After Treatment Initiation to Unravel the Role of Naturally Occurring Extracellular Vesicles in HIV Infection (Saturne-HIV)

This study aims to evaluate the role of extracellular vesicles in HIV-infection, by determining the expression profile and content of EVs before and after treatment initiation in HIV-infected patients, through extensive blood and tissue sampling (leukapheresis, stool sampling and colon biopsies). A one-time sampling (blood, stool, colon biopsies) will also be performed in HIV-seronegative healthy volunteers to confirm that results found in HIV-infected patients are related to the disease.

Study Overview

• Status: Recruiting
• Conditions: Hiv

• Study Type: Observational
• Enrollment (Estimated): 105

Contacts and Locations

• Study Contact: Name: Linos Vandekerckhove, Prof. Dr.; Phone Number: +3293323398; Email: linos.vandekerckhove@ugent.be

Study Locations

• Belgium
  • Oost-Vlaanderen
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • Recruiting
      • Ghent University Hospital
      • Contact: Linos Vandekerckhove, Prof. Dr.; Phone Number: +3293323398; Email: linos.vandekerckhove@ugent.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Our aim is to enroll a minimum of 32 and a maximum of 50 untreated HIV-infected patients. We aim to include a minimum of 16 patients with a CD4 T cell count lower than 350 cells/µl and a minimum of 16 patients with a CD4 T cell count higher than 350 cells/µl. Of the HIV-infected patients, we aim to include 12 patients undergoing additional sampling consisting of lymph node excisions and an ileocolonoscopy (see below).

Furthermore we aim to include 55 HIV-negative "healthy donors", from which we will collect inguinal lymph node samples, gut biopsies, a blood draw or leukapheresis and stool sample to confirm that the results found in HIV-patients are related to the disease. HIV seronegative participants can choose which procedures they would like to undergo, it is not necessary to undergo all study-related procedures. Before sampling, patients and healthy volunteers willing to participate will be enrolled following informed consent.

Description

A. HIV-infected individuals

A.1. Inclusion Criteria:

• Documented untreated HIV-1 infection defined as followed: HIV-1-specific antibody+(western blot); p31+ (ELISA)
• CD4 T cell count will be determined standard of care (SOC). A minimum of 16 patients will be included with a CD4 T cell count lower than 350 cells/µl and a minimum of 16 patients with a CD4 T cell count higher than 350 cells/µl
• Able and willing to provide written informed consent
• Age ≥ 18 years and ≤ 65 years
• Ability to attend the complete schedule of assessments and patient visits as described in the schedule below
• Ability and willingness to have blood, stool and colon samples collected and stored for 20 years after finalizing the study, and used for various research purposes

A.2. Exclusion Criteria:

• Recent HIV-infection, early diagnosis
• Previous or current history of opportunistic infection (AIDS defining events as defined in category C of the CDC clinical classification), consisting of chronic HIV-1 infection
• Evidence of active HBV infection (Hepatitis B surface antigen positive or HBV viral load positive in the past and no evidence of subsequent seroconversion (=HBV antigen or viral load negative and positive HBV surface antibody))
• Evidence of active HCV infection: HCV antibody positive result within 60 days prior to study entry with positive HCV viral load or, if the HCV antibody result is negative, a positive HCV RNA result within 60 days prior to study entry
• Current or known history of cardiomyopathy or significant ischemic or cerebrovascular disease
• Current or known history of cancer
• Pregnancy or breastfeeding
• Any conditions, including preexisting psychiatric and psychological disorders, which will in the opinion of the investigator interfere with the trial conduct or safety of the participant. An initial psychiatric assessment will be made by the treating physician. Since making a correct psychological assessment at the time of diagnosis can be difficult, a visit with a psychologist is planned for patients included in the study, for a second evaluation. This will be planned within the first month after diagnosis. In consultation with the psychologist, further sampling will be planned or the patient will be excluded from further sampling.
• Previous participation in a trial evaluating an immune modulating agent

• Abnormal laboratory tests results at screening:

  1. Confirmed hemoglobin <11g/dl for women and <12 g/dl for men
  2. Confirmed platelet count < 100 000/µl
  3. Confirmed neutrophil count <1000/μl
  4. Confirmed AST and/or ALT > 10x ULN
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
• Acute or serious illness, in the opinion of the site investigator, requiring systemic treatment and/or hospitalization within 60 days prior to entry
• Known inflammatory bowel disease (Crohn's disease or ulcerative colitis)

B. Healthy Volunteers

B.1. Inclusion Criteria:

• Able and willing to provide written informed consent
• Age ≥ 18 years and ≤ 65 years
• Ability to attend the complete sampling schedule, as described below
• Ability and willingness to have blood, stool and colon samples collected and stored for 20 years and used for various research purposes

B.2. Exclusion Criteria:

• HIV-infection
• Evidence of active HBV infection (Hepatitis B surface antigen positive or HBV viral load positive in the past and no evidence of subsequent seroconversion (=HBV antigen or viral load negative and positive HBV surface antibody))
• Evidence of active HCV infection: HCV antibody positive result within 60 days prior to study entry with positive HCV viral load or, if the HCV antibody result is negative, a positive HCV RNA result within 60 days prior to study entry
• Current or known history of cardiomyopathy or significant ischemic or cerebrovascular disease
• Current or known history of cancer
• Pregnancy or breastfeeding
• Any conditions, including preexisting psychiatric and psychological disorders, which will in the opinion of the investigator interfere with the trial conduct or safety of the participant
• Previous participation in a trial evaluating an immune modulating agent

• Abnormal laboratory tests results at screening:

  1. Confirmed hemoglobin <11g/dl for women and <12 g/dl for men
  2. Confirmed platelet count < 100 000/µl
  3. Confirmed neutrophil count <1000/μl
  4. Confirmed AST and/or ALT > 10xULN
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
• Acute or serious illness, in the opinion of the site investigator, requiring systemic treatment and/or hospitalization within 60 days prior to entry
• Known inflammatory bowel disease (Crohn's disease or ulcerative colitis)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
HIV-infected individuals
HIV-seronegative healthy volunteers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extracellular Vesicles analysis-NTA	Extracellular vesicles (EV) will be isolated through a combination of size-exclusion chromatography (SEC) and Optiprep density gradient (ODG). Nanoparticle Tracking Analysis (NTA) will be performed to obtain the concentration and size distribution of EVs in the samples.	6 years
Extracellular Vesicles analysis-microscopy	The isolated EVs will be further visualized by (electron) microscopy.	6 years
Extracellular Vesicles analysis-western blot	The isolated EVs will be further characterized through western blot.	6 years
Extracellular Vesicles analysis-PCR	The isolated EVs will be further characterized through PCR.	6 years
Extracellular Vesicles analysis-proteomics	The isolated EVs will be further characterized through proteomic analysis.	6 years
Extracellular Vesicles analysis-RNAsequencing	The isolated EVs will be further characterized through RNA sequencing.	6 years
Extracellular Vesicles analysis-reporter assays	Reporter assays will be performed to quantitatively measure bacterial EV-associated lipopolysaccharide (LPS).	6 years
Quantification of HIV DNA and RNA	Digital PCR	6 years
Immunological analysis-FACS	Immunophenotyping by flow cytometric assays will be performed of different cells to assess the phenotype of innate immune cells, using FACS analysis.	6 years
Immunological analysis-ELISA	Immunophenotyping by flow cytometric assays will be performed of different cells to assess the phenotype of innate immune cells, using ELISA.	6 years
Gene expression analysis/transcriptomics		6 years
Microbiome monitoring	Gut microbiome will be analyzed in stool and colon biopsies using next-generation sequencing (NGS) of rRNA gene amplicons to identify bacteria at genus/species level	6 years
Virological analysis-FLIPS	HIV will be characterized by Full Length Individual Proviral Sequencing (FLIPS).	6 years
Virological analysis-integration site	HIV will be characterized by integration site analysis.	6 years

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Linos Vandekerckhove, Prof. Dr., University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2021
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: October 23, 2020
• First Submitted That Met QC Criteria: November 26, 2020
• First Posted (Actual): December 4, 2020

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: HIV; Extracellular Vesicles
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections
• Other Study ID Numbers: BC-08408

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No