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

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.

Study Overview

• Status: Recruiting
• Conditions: Hiv

• Study Type: Observational
• Enrollment (Estimated): 25

Contacts and Locations

• Study Contact: Name: Sofie Rutsaert; Phone Number: +32 9 332 06 98; Email: sofierutsaert@hotmail.com

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Recruiting
    • Ghent University Hospital
    • Contact: Sofie Rutsaert; Phone Number: +32 9 332 06 98; Email: sofierutsaert@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

HIV-1 positive persons

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
HIV-1 positive persons

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of HIV DNA and RNA	Digital PCR	5 years
Integration site analysis	HIV/host DNA junctions will be amplified using the Integration Site Loop Amplification (ISLA) assay, and resulting chimeric amplicons will be sequenced by Sanger.	5 years
Full-length HIV genome analysis	Full-Length Individual Proviral Sequencing (FLIPS) assay: nested PCR with Illumina MiSeq.	5 years
Epigenetic analysis	Methylation (bisulfite conversion) and chromatin accessibility (Assay for Transposase-Accessible Chromatin using sequencing)	5 years
Transcriptome analysis	Bulk RNA sequencing on extracted RNA (Illumina Hiseq 2500 with 10-100 ng input of ribodepleted RNA); Single cell RNA sequencing (10x genomics technology )	5 years
High dimensional phenotyping	CyTOF (mass cytometry, Fluidigm) combined with bioinformatics approach to extensively characterize the phenotype of latently infected cells	5 years
Immunohistochemistry, RNA- and DNA In Situ Hybridization	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	5 years
Extracellular vesicles analysis	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.	5 years
Immunometabolic profile analysis	Mass spectrometry metabolomics will be used to study the immunometabolic profile of latently infected cells	5 years
p24 quantification	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.	5 years
Detection of translation-competent reservoirs	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.	5 years

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Linos Vandekerckhove, MD PhD, University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 21, 2020
• First Submitted That Met QC Criteria: March 11, 2020
• First Posted (Actual): March 12, 2020

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: HIV; Latency; Latency reversing agents; Latency reversal
• Additional Relevant MeSH Terms: Infections
• Other Study ID Numbers: BC-07056

Drug and device information, study documents

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