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

NCT04653610 | Recruiting

• 1 other identifier: BC-08408
• Study Type: observational
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hiv

Keywords

HIV; Extracellular Vesicles

Outcome Measures

Primary Outcomes (14)

• 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

Study Arms (2)

HIV-infected individuals

HIV-seronegative healthy volunteers

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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:
• Confirmed hemoglobin \<11g/dl for women and \<12 g/dl for men
• Confirmed platelet count \< 100 000/µl
• Confirmed neutrophil count \<1000/μl
• 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

Sponsors & Collaborators

• University Hospital, Ghent: lead

Study Sites (1)

Ghent University Hospital

Ghent, Oost-Vlaanderen, 9000, Belgium

RECRUITING

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Linos Vandekerckhove, Prof. Dr.

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Linos Vandekerckhove, Prof. Dr.

CONTACT

+3293323398; linos.vandekerckhove@ugent.be

Study Design

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

Study Record Dates

• First Submitted: October 23, 2020
• First Posted: December 4, 2020
• Study Start: January 27, 2021
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 8, 2024

Record last verified: 2024-02

Locations

BE (1)