HIV InfectionsEX VIVONCT05215704
Ex Vivo Characterization and Targeting of the Latent HIV Infected Reservoir to Cure HIV
An observational study of HIV Infections and HIV-1-infection, run by Erasmus Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections, HIV-1-infection, HIV-2 Infection
- How many people
- 40 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Jan 2012to 31 Dec 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Otherwise healthy adult HIV infected patients will be recruited at the Erasmus MC outpatient clinic of infectious diseases
Who may be able to join
- Age 18 years or older.
- Confirmed HIV-1 or HIV-2 infection.
Who cannot join
- Inability to place 2.5 cm venous catheter or perform phlebotomy
- Major comorbidities:
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Casper Rokx, MD PhD contact
Rob Gruters, PhD contact
Netherlands1 site, 1 recruiting
- Recruiting
Erasmus Medical Centre
Rotterdam
Rokx Casper, MD PhD
Casper Rokx, MD PhD
About this study
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).
Read the 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)
- Conditions
- HIV Infections, HIV-1-infection, HIV-2 Infection
- Keywords
- HIV, HIV cure, HIV reservoir
- Medical subject headings
- HIV Infections
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of HIV patients with a measurable proviral reservoir measured by molecular, flowcytometric and culture based assays
Measured: 10-15 years
Secondary outcomes (6)
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.
Measured: 10-15 years
The HIV reservoir size and activity as assessed by molecular, flowcytometric, and culture based assays ex vivo.
Measured: 10-15 years
The HIV reservoir susceptibility to shock and kill strategies as assessed by molecular, flowcytometric, and culture based assays.
Measured: 10-15 years
The HIV reservoir size, activity, and susceptibility to shock and kill strategies in relation to clinical phenotypes.
Measured: 10-15 years
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.
Measured: 10-15 years
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.
Measured: 10-15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2022
- Study start1 Jan 2012
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Casper Rokx, Erasmus Medical Center
- Investigators
- Casper Rokx, MD PhD, Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05215704
- Sponsor's protocol ID
- NL42819.078.12
- Acronym
- EX VIVO
- Status last verified
- Feb 2024
- First submitted
- 15 Dec 2021
- Last updated
- 14 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ex Vivo Characterization and Targeting of the Latent HIV Infected Reservoir to Cure HIV
- ClinicalTrials.gov ID
- NCT05215704
- Acronym / sponsor ID
- EX VIVO / NL42819.078.12
- Conditions
- HIV Infections, HIV-1-infection, HIV-2 Infection
- Keywords
- HIV, HIV cure, HIV reservoir
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Study start
- 1 Jan 2012 (actual)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 31 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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)
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Otherwise healthy adult HIV infected patients will be recruited at the Erasmus MC outpatient clinic of infectious diseases
Key inclusion criteria (2 listed)
- Age 18 years or older.
- Confirmed HIV-1 or HIV-2 infection.
Key exclusion criteria (4 listed)
- Inability to place 2.5 cm venous catheter or perform phlebotomy
- Major comorbidities:
- The inability to participate due to any other relevant medical, social, environmental, psychological, factors or according to the HIV treating physician's judgement
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The number of HIV patients with a measurable proviral reservoir measured by molecular, flowcytometric and culture based assays
Time frame: 10-15 years
6 secondary outcomes
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
The HIV reservoir size and activity as assessed by molecular, flowcytometric, and culture based assays ex vivo.
Time frame: 10-15 years
The HIV reservoir susceptibility to shock and kill strategies as assessed by molecular, flowcytometric, and culture based assays.
Time frame: 10-15 years
The HIV reservoir size, activity, and susceptibility to shock and kill strategies in relation to clinical phenotypes.
Time frame: 10-15 years
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
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Casper Rokx, MD PhD contact
Rob Gruters, PhD contact
Casper Rokx, MD PhD principal investigator
Erasmus Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV Infections and HIV-1-infection, run by Erasmus Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Casper Rokx, MD PhD (c.rokx@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of HIV patients with a measurable proviral reservoir measured by molecular, flowcytometric and culture based assays (time frame: 10-15 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2024.