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HIV Study on MEasuring the Reservoir on Cellular Level to CUre Infection (HIV-Mercuri)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04305665
Recruitment Status : Not yet recruiting
First Posted : March 12, 2020
Last Update Posted : March 18, 2020
Sponsor:
Information provided by (Responsible Party):
University Hospital, Ghent

Brief Summary:
The aim of this study is to gain new insights into HIV latency and reversal through extensive blood and tissues sampling (lymph node and colon biopsies) from 25 individuals under ART.

Condition or disease
Hiv

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Study Type : Observational
Estimated Enrollment : 25 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: HIV Study on MEasuring the Reservoir on Cellular Level to CUre Infection
Estimated Study Start Date : April 1, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Group/Cohort
HIV-1 positive persons



Primary Outcome Measures :
  1. Quantification of HIV DNA and RNA [ Time Frame: 5 years ]
    Digital PCR

  2. Integration site analysis [ Time Frame: 5 years ]
    HIV/host DNA junctions will be amplified using the Integration Site Loop Amplification (ISLA) assay, and resulting chimeric amplicons will be sequenced by Sanger.

  3. Full-length HIV genome analysis [ Time Frame: 5 years ]
    Full-Length Individual Proviral Sequencing (FLIPS) assay: nested PCR with Illumina MiSeq.

  4. Epigenetic analysis [ Time Frame: 5 years ]
    Methylation (bisulfite conversion) and chromatin accessibility (Assay for Transposase-Accessible Chromatin using sequencing)

  5. Transcriptome analysis [ Time Frame: 5 years ]
    • Bulk RNA sequencing on extracted RNA (Illumina Hiseq 2500 with 10-100 ng input of ribodepleted RNA)
    • Single cell RNA sequencing (10x genomics technology )

  6. High dimensional phenotyping [ Time Frame: 5 years ]
    CyTOF (mass cytometry, Fluidigm) combined with bioinformatics approach to extensively characterize the phenotype of latently infected cells

  7. Immunohistochemistry, RNA- and DNA In Situ Hybridization [ Time Frame: 5 years ]
    Immunochemistry will be used to study the expression of activation and exhaustion markers on tissues samples , while viral expression will be assessed through DNAScope and RNAScope technologies

  8. Extracellular vesicles analysis [ Time Frame: 5 years ]
    Extracellular vesicles (EV) will be isolated through size-exclusion chromatography (SEC) and Optiprep density gradient (ODG). The isolated EVs will be visualized by microscopy, western blot and PCR. Proteomics and RNA sequencing will be performed to assess the EV content.

  9. Immunometabolic profile analysis [ Time Frame: 5 years ]
    Mass spectrometry metabolomics will be used to study the immunometabolic profile of latently infected cells

  10. p24 quantification [ Time Frame: 5 years ]
    p24 SIMOA assay: ultra-sensitive digital immunoassay providing 1000 times improvement in detection limits compared with a traditional ELISA. This assay will be used to assess the capacity of various latency reversing agents and immunomodulators at reactivating HIV from latency.

  11. Detection of translation-competent reservoirs [ Time Frame: 5 years ]
    HIV-Flow assay: flow cytometry based assay using a combination of 2 antibodies targeting the p24 protein and allowing the detection of cells containing translation-competent viruses. p24+ cells detected by this assay can be sorted for downstream applications and further characterization of translation-competent reservoirs.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
HIV-1 positive persons
Criteria

Inclusion Criteria:

  • Documented HIV-1 subtype B infection
  • Able and willing to provide written informed consent
  • Age = or >18 years and < 65 years
  • CD4 count at screening > 350/μl
  • Viral load < 40 copies/ml determined by CobasTaqMan HIV-1 test v2.0 assay for at least 2 years (one blip < 200 copies/ml is allowed)
  • Ability and willingness to have blood and tissue samples collected and stored for 20 years and used for various research purposes.

Exclusion Criteria:

  • 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.
  • History of HIV-related thrombocytopenia.
  • 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 results of standard of care laboratory tests:

    1. Confirmed haemoglobin <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.
  • The following treatment will be prohibited three months before screening and during the study:

    1. immunosuppressive drugs (inclusive corticosteroids) except for drugs used for topical use.
    2. Immunomodulatory drugs including but not limited to Granulocyte-colony stimulating factors, Granulocyte-monocyte colony-stimulating factor, interleukin 2, 7 & 15.

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Responsible Party: University Hospital, Ghent
ClinicalTrials.gov Identifier: NCT04305665    
Other Study ID Numbers: BC-07056
First Posted: March 12, 2020    Key Record Dates
Last Update Posted: March 18, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Ghent:
HIV
Latency
Latency reversing agents
Latency reversal
Additional relevant MeSH terms:
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Infection