NCT04305665

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
25

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Jun 2020

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 21, 2020

Completed
20 days until next milestone

First Posted

Study publicly available on registry

March 12, 2020

Completed
3 months until next milestone

Study Start

First participant enrolled

June 24, 2020

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2024

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2025

Completed
Last Updated

January 31, 2024

Status Verified

January 1, 2024

Enrollment Period

4.5 years

First QC Date

February 21, 2020

Last Update Submit

January 30, 2024

Conditions

Hiv

Keywords

HIVLatencyLatency reversing agentsLatency reversal

Outcome Measures

Primary Outcomes (11)

  • 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

Study Arms (1)

HIV-1 positive persons

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

HIV-1 positive persons

You may qualify if:

  • 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.

You may not qualify if:

  • 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:
  • 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.
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Ghent University Hospital

Ghent, 9000, Belgium

RECRUITING

Related Publications (1)

  • Delporte M, Lambrechts L, Blomme EE, van Snippenberg W, Rutsaert S, Verschoore M, De Smet E, Noppe Y, De Langhe N, De Scheerder MA, Gerlo S, Vandekerckhove L, Trypsteen W. Integrative Assessment of Total and Intact HIV-1 Reservoir by a 5-Region Multiplexed Rainbow DNA Digital PCR Assay. Clin Chem. 2025 Jan 3;71(1):203-214. doi: 10.1093/clinchem/hvae192.

    PMID: 39749517DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV InfectionsBlood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Study Officials

  • Linos Vandekerckhove, MD PhD

    University Hospital, Ghent

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Sofie Rutsaert

CONTACT

+32 9 332 06 98sofierutsaert@hotmail.com

Study Design

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

Study Record Dates

First Submitted

February 21, 2020

First Posted

March 12, 2020

Study Start

June 24, 2020

Primary Completion

December 31, 2024

Study Completion

December 31, 2025

Last Updated

January 31, 2024

Record last verified: 2024-01

Locations

BE(1)