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

Recruiting

• Conditions: Hiv

• Registration Number: NCT04305665
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-02-21
• Study First Submitted QC: 2020-03-11
• Study First Posted: 2020-03-12
• Study Start: 2020-06-24
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-30
• Last Update Posted: 2024-01-31
• Primary Completion: 2024-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 25

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Quantification of HIV DNA and RNA	5 years	Digital PCR
Epigenetic analysis	5 years	Methylation (bisulfite conversion) and chromatin accessibility (Assay for Transposase-Accessible Chromatin using sequencing)
Integration site analysis	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.
Full-length HIV genome analysis	5 years	Full-Length Individual Proviral Sequencing (FLIPS) assay: nested PCR with Illumina MiSeq.
High dimensional phenotyping	5 years	CyTOF (mass cytometry, Fluidigm) combined with bioinformatics approach to extensively characterize the phenotype of latently infected cells
Immunohistochemistry, RNA- and DNA In Situ Hybridization	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
Detection of translation-competent reservoirs	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.
Transcriptome analysis	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 )
Immunometabolic profile analysis	5 years	Mass spectrometry metabolomics will be used to study the immunometabolic profile of latently infected cells
Extracellular vesicles analysis	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.
p24 quantification	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.

Trial Locations

Locations (1)

Ghent University Hospital; 🇧🇪 Ghent, Belgium