Measuring the HIV-1 Reservoir During Cure Interventions Studies (MERCI)

NCT05783388 | Withdrawn

• 1 other identifier: ONZ-2022-0054 - MERCI
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is the gain new insights into HIV latency before and after cure intervention studies through extensive blood and tissue sampling (lymph node and colon biopsies) from 30 individuals.

Conditions

Hiv

Keywords

HIV; Latency

Outcome Measures

Primary Outcomes (14)

• Quantification of total and intact HIV DNA and HIV RNA

  Rainbow assay: multiplex digital PCR approach that combines five different HIV-1 regions to quantify total HIV-1 DNA and intact HIV-1 DNA simultaneously (Qiacuity dPCR platform, Qiagen). mutliplex digital PCR approach to quantify HIV RNA

  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

• Matched integration site and proviral sequencing

  MIP-seq: captures full-length viral genome sequences in conjunction with its associated viral integration site

  5 years

• Proviral UMI-mediated Long-read Sequencing

  HIV-PULSE: characterize the composition of the viral reservoir using long-read sequencing. Involves pre-amplifying individual proviral genomes using PCR and tagging them with dual UMIs, followed by long-range PCR amplification and long-read sequencing on the Oxford Nanopore MinION platform

  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

• Immunometabolic profile analysis

  Mass spectrometry metabolomics will be used to study the immunometabolic profile of latently infected cells

  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. The Simultaneous TCR Integration site and Provirus sequencing (STIP-seq) assay will be performed to sequence the proviral genome and matched integration sites of the translation-competent viruses, as well as phenotypic characterization and TCR sequencing of the host cell. characterization of translation-competent reservoirs.

  5 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.

  5 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.

  5 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

  5 years

Study Arms (1)

HIV-1 positive persons

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

HIV-1 positive persons who are included in a cure intervention study

You may not qualify if:

• 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 history of 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 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.

Sponsors & Collaborators

• University Hospital, Ghent: lead

Study Sites (1)

Ghent University Hospital

Ghent, 9000, Belgium

Location

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, MD PhD

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: March 24, 2023
• Study Start: June 1, 2023
• Primary Completion: February 1, 2025
• Study Completion (Estimated): February 1, 2030
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

BE (1)