Analyzing the Role of Extracellular Vesicles in HIV Infection

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

This study looks at how tiny particles in the blood, called extracellular vesicles, behave in people with HIV before and after starting treatment to see if they can help us understand the infection better.

Quick facts

• Study type: Observational
• Enrollment: 105 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: University Hospital, Ghent (other)
• Locations: 1 site (Ghent, Oost-Vlaanderen)
• Trial ID: NCT04653610 on ClinicalTrials.gov

What this trial studies

This observational study evaluates the role of extracellular vesicles (EVs) in HIV infection by analyzing their expression profile and content before and after treatment initiation. It involves extensive blood and tissue sampling, including leukapheresis, stool sampling, and colon biopsies from HIV-infected patients. Additionally, a one-time sampling will be conducted on HIV-seronegative healthy volunteers to establish a baseline for comparison. The study aims to deepen the understanding of EVs in the context of HIV and their potential implications for treatment.

Who should consider this trial

Good fit: Ideal candidates include HIV-infected individuals aged 18 to 65 with documented untreated HIV-1 infection and varying CD4 T cell counts.

Not a fit: Patients with recent HIV infection or a history of opportunistic infections may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance the understanding of HIV infection mechanisms and lead to improved treatment strategies.

How similar studies have performed: While the specific approach of analyzing EVs in HIV is novel, similar studies have shown promise in understanding the role of extracellular vesicles in other diseases.

Eligibility criteria

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)

Where this trial is running

Ghent, Oost-Vlaanderen

• Ghent University Hospital — Ghent, Oost-Vlaanderen, Belgium (RECRUITING)

Study contacts

• Principal investigator: Linos Vandekerckhove, Prof. Dr. — University Hospital, Ghent
• Study coordinator: Linos Vandekerckhove, Prof. Dr.

Conditions: Hiv, HIV, Extracellular Vesicles