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Ex Vivo Characterization and Targeting of the Latent HIV Infected Reservoir to Cure HIV (EX VIVO)

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ClinicalTrials.gov Identifier: NCT05215704
Recruitment Status : Recruiting
First Posted : January 31, 2022
Last Update Posted : January 31, 2022
Information provided by (Responsible Party):
Casper Rokx, Erasmus Medical Center

Brief Summary:

Combination antiretroviral therapy (cART) blocks intracellular human immunodeficiency virus (HIV) replication in CD4+ T-lymphocytes, but fails to eliminate latent HIV infected CD4+ T-lymphocytes. About 7 (range <1-100) in 106 of these cells are latently infected and can cause reactivation of proviral HIV when cART is stopped. These latently infected cells form the reservoir and must be targeted in order to cure HIV. We would like to further investigate this reservoir and assess potential interventions to eradicate it. One promising option is to further study the influence of HIV latency disruptors (latency reversing agents, LRA) on the HIV infected reservoir. These agents are used in shock and kill strategies that disrupt latency by LRA followed by the selective (induced) killing of the reservoir cell due to viro-pathogenic effects.

For accurate assessment of the reservoir and potential cure strategies, including the impact of LRA on the reservoir, a large reservoir and sufficient cells for analysis are desirable. Our understanding on the reservoir comes from in vitro lymphocyte models and early ex vivo studies. Additional studies of patients with different clinical phenotypes including untreated versus treated versus the rare individuals that control HIV spontaneously are increasingly relevant to the field. Especially this last category represent biological examples of viral control without cART and are useful to study the factors that set them apart from those that need treatment for their HIV. This study aims to deepen our understanding of the HIV reservoir and cure strategies, foremost, shock and kill strategies. We will do this by setting up a durable ex vivo platform for HIV reservoir and cure studies of which the samples can be used for hypothesis generation for in-vivo studies.

A project from the Erasmus MC HIV Eradication Group (EHEG).

Condition or disease
HIV Infections HIV-1-infection HIV-2 Infection

Detailed Description:

This is a prospective cross-sectional cohort study used for ex vivo studies using material from HIV infected individuals. Peripheral blood mononuclear cells (PBMC's) and whole blood are obtained through leukapheresis and blood sampling at a single timepoint. Relevant clinical data will be collected to support interpretation of ex vivo experimental results. In vitro experiments are performed on patient derived material. In a substudy, patients can consent to longitudinal follow up with yearly sampling for 4 years.

Reservoir characteristics and efficacy of shock and kill strategies as defined in the endpoints will be explored between patients with different HIV clinical phenotypes. This allows us to identify discriminative factors useful to develop future cure strategies in clinic. We will therefore aim to include the following patients groups in the cohort:

  • HIV-1 patients including B and non-B subtypes patients
  • HIV-2 patients
  • Long term non progressors (plasma HIV-RNA <2000c/mL without cART)
  • Elite controllers (plasma HIV-RNA <50c/mL without cART)
  • Post-treatment controller (plasma HIV-RNA <2000c/mL after permanent cART interruption)

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Ex Vivo Characterization and Targeting of the Latent HIV Infected Reservoir to Cure HIV
Actual Study Start Date : January 1, 2012
Estimated Primary Completion Date : December 31, 2030
Estimated Study Completion Date : December 31, 2030

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Primary Outcome Measures :
  1. The number of HIV patients with a measurable proviral reservoir measured by molecular, flowcytometric and culture based assays [ Time Frame: 10-15 years ]

Secondary Outcome Measures :
  1. The level of reactivation of latently HIV infected PBMCs after treatment ex vivo with established and novel HIV cure compounds (alone and in combination) as assessed by cell-associated HIVRNA. [ Time Frame: 10-15 years ]
  2. The HIV reservoir size, activity and susceptibility to shock and kill strategies as assessed by molecular, flowcytometric and culture based assay ex vivo and in relation to clinical phenotypes. [ Time Frame: 10-15 years ]
  3. To measure predictive biomarkers of the size and activity of the latent HIV reservoir as assessed by molecular, flowcytometric and culture based assay ex vivo. [ Time Frame: 10-15 years ]
  4. The number of newly setup assays that measure the size of the proviral reservoir and are validated with current established molecular, flowcytometric and culture based assays. [ Time Frame: 10-15 years ]

Biospecimen Retention:   Samples With DNA
Blood samples and leucapheresis

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Otherwise healthy adult HIV infected patients will be recruited at the Erasmus MC outpatient clinic of infectious diseases

Inclusion Criteria:

  1. Age 18 years or older.
  2. Confirmed HIV-1 or HIV-2 infection.

Exclusion Criteria:

  1. Inability to place 2.5 cm venous catheter or perform phlebotomy
  2. Major comorbidities:

    A. Severe symptomatic anemia B. Recent symptomatic cardiovascular event (unstable angina pectoris, decompensated heart failure, myocardial infarction).

  3. The inability to participate due to any other relevant medical, social, environmental, psychological, factors or according to the HIV treating physician's judgement

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05215704

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Contact: Casper Rokx, MD PhD c.rokx@erasmusmc.nl
Contact: Rob Gruters, PhD r.gruters@erasmusmc.nl

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Erasmus Medical Centre Recruiting
Rotterdam, Netherlands
Contact: Rokx Casper, MD PhD         
Principal Investigator: Casper Rokx, MD PhD         
Principal Investigator: Tokameh Mahmoudi, PhD         
Principal Investigator: Rob Gruters, PhD         
Principal Investigator: Peter Katsikis, Prof         
Sub-Investigator: Shringar Rao, PhD         
Sub-Investigator: Raquel Crespo Galvan, MSc         
Sub-Investigator: Shahla Romal         
Sub-Investigator: Tonmoy Hossain, MSc         
Sub-Investigator: Henrieke Prins, MD         
Sub-Investigator: Albert Groenendijk, MD         
Sub-Investigator: Kathryn Hensley, MD         
Sub-Investigator: Cynthia Lungu, MSc         
Sub-Investigator: Peter te Boekhorst, MD PhD         
Sub-Investigator: Yvonne Muller, PhD         
Sub-Investigator: Els van Nood, MD PhD         
Sub-Investigator: Mariana Mendonca melo, MD         
Sub-Investigator: Annelies Verbon, Prof         
Sub-Investigator: Jeroen van Kampen, MD PhD         
Sub-Investigator: David vd Vijver, PharmD PhD         
Sub-Investigator: Birgit Koch, Prof         
Sub-Investigator: Thibault Mespede, PhD         
Sponsors and Collaborators
Erasmus Medical Center
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Principal Investigator: Casper Rokx, MD PhD Erasmus Medical Center
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Responsible Party: Casper Rokx, Principal Investigator, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT05215704    
Other Study ID Numbers: NL42819.078.12
First Posted: January 31, 2022    Key Record Dates
Last Update Posted: January 31, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Casper Rokx, Erasmus Medical Center:
HIV cure
HIV reservoir
Additional relevant MeSH terms:
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Communicable Diseases
Disease Attributes
Pathologic Processes