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

Hiv Clinical Trial

Official title:

Measuring the HIV-1 Reservoir During Cure Interventions Studies

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05783388
• Other study ID #: ONZ-2022-0054 - MERCI
• Status: Withdrawn
• Start date: June 2023
• Est. completion date: February 2030

Study information

• Verified date: August 2023
• Source: University Hospital, Ghent
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 2030
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Meets the inclusion criteria of the cure intervention study

Exclusion Criteria:

• 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:

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.

Related Conditions & MeSH terms

• Hiv

Locations

Country	Name	City	State
Belgium	Ghent University Hospital	Ghent

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Ghent

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Full-length HIV genome analysis	Full-Length Individual Proviral Sequencing (FLIPS) assay: nested PCR with Illumina MiSeq.	5 years
Primary	Epigenetic analysis	Methylation (bisulfite conversion) and chromatin accessibility (Assay for Transposase-Accessible Chromatin using sequencing)	5 years
Primary	Matched integration site and proviral sequencing	MIP-seq: captures full-length viral genome sequences in conjunction with its associated viral integration site	5 years
Primary	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
Primary	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
Primary	High dimensional phenotyping	CyTOF (mass cytometry, Fluidigm) combined with bioinformatics approach to extensively characterize the phenotype of latently infected cells	5 years
Primary	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
Primary	Immunometabolic profile analysis	Mass spectrometry metabolomics will be used to study the immunometabolic profile of latently infected cells	5 years
Primary	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
Primary	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
Primary	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
Primary	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