HIV Study on MEasuring the Reservoir on Cellular Level to CUre Infection

Hiv Clinical Trial

— HIV-Mercuri  

Official title:

HIV Study on MEasuring the Reservoir on Cellular Level to CUre Infection

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04305665
• Other study ID #: BC-07056
• Status: Recruiting
• Start date: June 24, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: January 2024
• Source: University Hospital, Ghent
• Contact: Sofie Rutsaert
• Phone: +32 9 332 06 98
• Email: sofierutsaert[@]hotmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hiv
• Infections

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 HIV DNA and RNA	Digital PCR	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	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	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
Primary	Immunometabolic profile analysis	Mass spectrometry metabolomics will be used to study the immunometabolic profile of latently infected cells	5 years
Primary	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
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.	5 years