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Immuno-virological Evaluation of Persons Living With HIV (PLWH)

Primary Purpose

HIV-1-infection, HIV Seropositivity

Status
Not yet recruiting
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
Leucapheresis
Sponsored by
University Hospital, Ghent
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for HIV-1-infection

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Cohort 1: short-term ART cohort Documented HIV-1 infection Able and willing to provide written informed consent Age = or >18 years and < 80 years ART started during a documented recent HIV-1 infection (acute HIV infection, defined as: Clinical symptoms of acute seroconversion and incomplete Western Blot, or Negative screening test within the past 6 months and incomplete Western Blot, or Risk contact within the <3 months and presumable primo-infection with or without clinical symptoms and incomplete Western Blot. Being on ART since minimum 2 years and maximum 10 years Participants should have had a routine plasma viral load measurement at least once a year. Viral load < 40 or <50 copies/ml determined by the assay (used in the local centers) for at least 3 years (one blip < 200 copies/ml is allowed) Ability and willingness to have blood samples collected and stored for 20 years and used for various research purposes. Patients with HIV-1 subtype B are preferred for inclusion (as most of the complex assays are subtype B specific). However, if the investigators do not reach our target of 10 participants, patients infected with other subtypes will be allowed to enter the study. (Primers will subsequently be adapted to the patient-specific proviral sequences). Cohort 2: long-term ART cohort Documented HIV-1 infection Able and willing to provide written informed consent Age = or >18 years and < 80 years Being on ART since at least 20 years ART should not have been started during a documented recent HIV-1 infection (acute HIV infection), defined as: Clinical symptoms of acute seroconversion and incomplete Western Blot or Negative screening test within the past 6 months and incomplete Western Blot or Risk contact within <3 months and presumable primo-infection with or without clinical symptoms and incomplete Western Blot. Patients should have had a routine plasma viral load measurement at least once a year. Routine plasma viral load < 40 or <50 copies/ml determined by the assay used in the local centres for at least 20 years (one blip < 200 copies/ml is allowed if it occurred >10 years ago) Ability and willingness to have blood samples collected and stored for 20 years and used for various research purposes. Participants with HIV-1 subtype B are preferred for inclusion (as most of the complex assays are subtype B specific). However, if the investigators do not reach our target of 10 participants, patients infected with other subtypes will be allowed to enter the study. (Primers will subsequently be adapted to the patient-specific proviral sequences). Exclusion Criteria: Previous or current history of opportunistic infection (AIDS defining events as defined in category C of the Centers for Disease Control and Prevention (CDC) clinical classification), consisting of chronic HIV-1 infection. Evidence of active Hepatitis B-virus (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 cancer. History of HIV-related thrombocytopenia. Pregnancy or breastfeeding. Any condition, including preexisting psychiatric and psychological disorders, which will in the opinion of the investigator interfere with the trial conduct or safety of the participant. Abnormal results of standard of care laboratory tests: Confirmed haemoglobin <11g/dl for women and <12 g/dl for men Confirmed platelet count <100 000/µl * Confirmed neutrophil count <1000/μl Confirmed Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)>10x upper limit of normal (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.

Sites / Locations

  • UZ Gent

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Immuno-virological evaluation of persons living with HIV

Arm Description

Leucapheresis will be performed in HIV positive people making white blood cells available for in depth virological and immunological evaluation

Outcomes

Primary Outcome Measures

Information on virological aspects of people on long term ART versus people treated during recent infection
Intact proviral deoxyribonucleic acid (DNA) assay quantified by digital Polymerase Chain Reaction (pcr)

Secondary Outcome Measures

Full Information

First Posted
July 13, 2023
Last Updated
September 26, 2023
Sponsor
University Hospital, Ghent
Collaborators
Vrije Universiteit Brussel, Centre Hospitalier Universitaire Saint Pierre, Centre Hospitalier Universitaire de Liege, Universitair Ziekenhuis Brussel, Université Libre de Bruxelles, KU Leuven
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1. Study Identification

Unique Protocol Identification Number
NCT05973825
Brief Title
Immuno-virological Evaluation of Persons Living With HIV (PLWH)
Official Title
Immuno-virological Evaluation of Persons Living With HIV (PLWH) Who Initiated Anti-retroviral Treatment (ART) During Acute HIV Infection and of PLWH on Long Term ART
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 13, 2023 (Anticipated)
Primary Completion Date
July 12, 2026 (Anticipated)
Study Completion Date
July 12, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Ghent
Collaborators
Vrije Universiteit Brussel, Centre Hospitalier Universitaire Saint Pierre, Centre Hospitalier Universitaire de Liege, Universitair Ziekenhuis Brussel, Université Libre de Bruxelles, KU Leuven

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a dual arm (arm 1 and arm 2) multi-centric non-randomized (prospective) study. Two new multicentric cohorts will be set up in 4 Belgian HIV reference centers (UZ Gent, UZ Brussel, University Hospital Liege and St. Pierre Hospital Brussels): cohort 1 will comprise PLWH in whom ART was initiated during acute HIV infection minimum 3 years ago but no more than 10 years ago (short-term ART cohort); cohort 2 will comprise PLWH on ART since >20 years (long-term ART cohort). Participants will be included based on suppressed viremia and uninterrupted ART since initiation. Participants will undergo one blood sampling and one leukapheresis. In and exclusion criteria are described below.
Detailed Description
This project aims to gain new knowledge and insights into the viral reservoir establishment and HIV Latency as well as to develop new powerful tools to study latency reversal, that will ultimately contribute to research into an HIV curative treatment. The study objectives are To collect and store state of the art peripheral blood samples (60 vials of 50 X106 PBMC's) from two patient cohorts, 10 acute seroconverters and 10 long-term ART-treated patients . To characterize and compare the latent reservoir in blood samples from both cohorts as for the proviral genome, transcriptome, epigenome and T cell receptor level To perform an immunological profiling of infected cells. To evaluate available drugs that induce either a block-and-lock or a shock-and-kill in in vitro interventions using blood samples from both cohorts To accelerate the negative selection of transcriptionally competent proviruses in vitro and determine the role of the different determinants. To make all data available for the different partners and integrate all data acquired.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV-1-infection, HIV Seropositivity

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Immuno-virological evaluation of persons living with HIV
Arm Type
Experimental
Arm Description
Leucapheresis will be performed in HIV positive people making white blood cells available for in depth virological and immunological evaluation
Intervention Type
Procedure
Intervention Name(s)
Leucapheresis
Intervention Description
leucapheresis is a procedure in which a large amount of blood cells are obtained by an apheresis procedure
Primary Outcome Measure Information:
Title
Information on virological aspects of people on long term ART versus people treated during recent infection
Description
Intact proviral deoxyribonucleic acid (DNA) assay quantified by digital Polymerase Chain Reaction (pcr)
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Cohort 1: short-term ART cohort Documented HIV-1 infection Able and willing to provide written informed consent Age = or >18 years and < 80 years ART started during a documented recent HIV-1 infection (acute HIV infection, defined as: Clinical symptoms of acute seroconversion and incomplete Western Blot, or Negative screening test within the past 6 months and incomplete Western Blot, or Risk contact within the <3 months and presumable primo-infection with or without clinical symptoms and incomplete Western Blot. Being on ART since minimum 2 years and maximum 10 years Participants should have had a routine plasma viral load measurement at least once a year. Viral load < 40 or <50 copies/ml determined by the assay (used in the local centers) for at least 3 years (one blip < 200 copies/ml is allowed) Ability and willingness to have blood samples collected and stored for 20 years and used for various research purposes. Patients with HIV-1 subtype B are preferred for inclusion (as most of the complex assays are subtype B specific). However, if the investigators do not reach our target of 10 participants, patients infected with other subtypes will be allowed to enter the study. (Primers will subsequently be adapted to the patient-specific proviral sequences). Cohort 2: long-term ART cohort Documented HIV-1 infection Able and willing to provide written informed consent Age = or >18 years and < 80 years Being on ART since at least 20 years ART should not have been started during a documented recent HIV-1 infection (acute HIV infection), defined as: Clinical symptoms of acute seroconversion and incomplete Western Blot or Negative screening test within the past 6 months and incomplete Western Blot or Risk contact within <3 months and presumable primo-infection with or without clinical symptoms and incomplete Western Blot. Patients should have had a routine plasma viral load measurement at least once a year. Routine plasma viral load < 40 or <50 copies/ml determined by the assay used in the local centres for at least 20 years (one blip < 200 copies/ml is allowed if it occurred >10 years ago) Ability and willingness to have blood samples collected and stored for 20 years and used for various research purposes. Participants with HIV-1 subtype B are preferred for inclusion (as most of the complex assays are subtype B specific). However, if the investigators do not reach our target of 10 participants, patients infected with other subtypes will be allowed to enter the study. (Primers will subsequently be adapted to the patient-specific proviral sequences). Exclusion Criteria: Previous or current history of opportunistic infection (AIDS defining events as defined in category C of the Centers for Disease Control and Prevention (CDC) clinical classification), consisting of chronic HIV-1 infection. Evidence of active Hepatitis B-virus (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 cancer. History of HIV-related thrombocytopenia. Pregnancy or breastfeeding. Any condition, including preexisting psychiatric and psychological disorders, which will in the opinion of the investigator interfere with the trial conduct or safety of the participant. Abnormal results of standard of care laboratory tests: Confirmed haemoglobin <11g/dl for women and <12 g/dl for men Confirmed platelet count <100 000/µl * Confirmed neutrophil count <1000/μl Confirmed Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)>10x upper limit of normal (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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Linos Vandekerckhove
Phone
+3293323398
Email
linos.vandekerckhove@ugent.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Linos vandekerckhove
Organizational Affiliation
UZ Gent
Official's Role
Principal Investigator
Facility Information:
Facility Name
UZ Gent
City
Gent
State/Province
Oost-Vlaanderen
ZIP/Postal Code
9000
Country
Belgium
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Linos Vandekerckhove
Phone
09333398
Email
linos.vandekerckhove@ugent.be

12. IPD Sharing Statement

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Immuno-virological Evaluation of Persons Living With HIV (PLWH)

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