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NCT Number: NCT05215704

Ex Vivo Characterization and Targeting of the Latent HIV Infected Reservoir to Cure HIV

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).

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Key information

Conditions

HIV Infections Blood-Borne Infections Communicable Diseases Genital Diseases HIV-1-infection HIV-2 Infection Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Urogenital Diseases Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Erasmus Medical Centre

Rotterdam, Netherlands

Location status: Recruiting

Location contact

Albert Groenendijk, MD

SUB_INVESTIGATOR

Annelies Verbon, Prof

SUB_INVESTIGATOR

Birgit Koch, Prof

SUB_INVESTIGATOR

Casper Rokx, MD PhD

PRINCIPAL_INVESTIGATOR

Cynthia Lungu, MSc

SUB_INVESTIGATOR

David vd Vijver, PharmD PhD

SUB_INVESTIGATOR

Els van Nood, MD PhD

SUB_INVESTIGATOR

Henrieke Prins, MD

SUB_INVESTIGATOR

Jeroen van Kampen, MD PhD

SUB_INVESTIGATOR

Kathryn Hensley, MD

SUB_INVESTIGATOR

Mariana Mendonca melo, MD

SUB_INVESTIGATOR

Peter Katsikis, Prof

PRINCIPAL_INVESTIGATOR

Peter te Boekhorst, MD PhD

SUB_INVESTIGATOR

Raquel Crespo Galvan, MSc

SUB_INVESTIGATOR

Rob Gruters, PhD

PRINCIPAL_INVESTIGATOR

Rokx Casper, MD PhD

CONTACT

Shahla Romal

SUB_INVESTIGATOR

Shringar Rao, PhD

SUB_INVESTIGATOR

Thibault Mespede, PhD

SUB_INVESTIGATOR

Tokameh Mahmoudi, PhD

PRINCIPAL_INVESTIGATOR

Tonmoy Hossain, MSc

SUB_INVESTIGATOR

Yvonne Muller, PhD

SUB_INVESTIGATOR

About this study

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)

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • Inability to place 2.5 cm venous catheter or perform phlebotomy
  • Major comorbidities:

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

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

Treatment and study plan

Primary outcomes

  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 outcomes

  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 and activity as assessed by molecular, flowcytometric, and culture based assays ex vivo.

    Time frame: 10-15 years

  3. The HIV reservoir susceptibility to shock and kill strategies as assessed by molecular, flowcytometric, and culture based assays.

    Time frame: 10-15 years

  4. The HIV reservoir size, activity, and susceptibility to shock and kill strategies in relation to clinical phenotypes.

    Time frame: 10-15 years

  5. 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

  6. 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

Study contacts

Contact information is provided by the study sponsor or research team.

Casper Rokx, MD PhD

CONTACT

[email protected]

Rob Gruters, PhD

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

Erasmus Medical Center

Other

Registry information

Acronym: EX VIVO

Important dates

Study start
2012
Primary completion
2030
Study completion
2030
First posted
Jan 31, 2022
Registry last updated
Feb 14, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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