- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT07745530
Platelets Target the Circulating HIV Reservoir: Implications for Immunological Failure (PLAQUAGE)
PLAQUAGE - Platelets Target the Circulating HIV Reservoir: Implications for Immunological Failure
HIV/AIDS is a chronic disease that is difficult to eradicate because the virus persists as proviral DNA integrated into the host cells. Despite antiretroviral therapy, proviral DNA persists in lymphoid and myeloid reservoirs, whether circulating (memory CD4+ T cells) or tissue-based (macrophages). HIV reservoirs are highly heterogeneous, making it difficult to identify a specific biomarker or cell profile for a given reservoir. A distinctive feature of HIV reservoirs may be the selective interaction between reservoir cells and platelets. The presence of HIV in platelets could impact disease progression, particularly by triggering the reversal of HIV latency and leading to residual viral production. The frequency of platelets containing circulating virus in the blood is approximately 0.1% of the total platelet volume. Although seemingly negligible, this would represent a daily input of 10⁸ platelets harboring the virus. Furthermore, patients whose platelets contain HIV are primarily those with persistent immunological failure, known as "immunological non-responders" (InR).
The regulation of the size (number and frequency) of the HIV reservoir by platelets is not known. However, HIV-containing platelets form more conjugates with CD4+ T cells than HIV-free platelets. While HIV-containing platelets do not productively infect cells, they induce metabolic dysfunction in CD4+ T cells (aerobic glycolysis). Increased aerobic glycolysis is a hallmark of T cell activation and senescence.
This suggests an interconnection between the presence of the virus in platelets, the size of the reservoir, and immune dysfunction in HIV.
Study Overview
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Jean-Jacques VITAGLIANO, PhD
- Phone Number: +33320694280
- Email: jjvitagliano@ch-tourcoing.fr
Study Contact Backup
- Name: VITAGLIANO
- Phone Number: 0320694280
- Email: jjvitagliano@ch-tourcoing.fr
Study Locations
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Tourcoing, France, 59200
- Recruiting
- Centre Hospitalier de Tourcoing
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Contact:
- Jean-Jacques Vitagliano, PhD
- Phone Number: 0320694280
- Email: jjvitagliano@ch-tourcoing.fr
-
Principal Investigator:
- Olivier Robineau, MD, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Adult patients living with HIV with an undetectable viral load for more than 2 years
- Beneficiary of a social security scheme or rightful claimant;
- Patients able to read and understand the information sheet;
- Having signed the consent form.
Exclusion Criteria:
- being unable to give free and informed consent;
- pregnant or breastfeeding woman;
- being under guardianship, curatorship, or a protection mandate;
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Immunological non-responders 1
Immunological non-responders (<500 CD4+ T cells/µL, undetectable viral load for >2 years) with a CD4+ T cell nadir below 100.
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During a routine consultation, a specific 40 mL blood sample will be collected for the study.
|
|
Experimental: Immunological responders
Immunological responders (>500 CD4+ T cells/µL, undetectable viral load for >2 years)
|
During a routine consultation, a specific 40 mL blood sample will be collected for the study.
|
|
Experimental: Immunological non-responders 2
Immunological non-responders (<500 CD4+ T cells/µL, undetectable viral load for >2 years) with a CD4+ T cell nadir between 200 and 500
|
During a routine consultation, a specific 40 mL blood sample will be collected for the study.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
In vivo evaluation of the formation of platelet-PBMC conjugates enriched in latent or active reservoirs and of their transcriptional competence
Time Frame: at enrollment
|
In vivo evaluation of the formation of platelet-PBMC conjugates enriched in latent or active reservoirs, correlated with immune status through the following parameters: Frequency of CD4+ T lymphocytes associated with platelets and/or platelet components, Frequency of platelet-associated CD4+ T cells carrying HIV RNA, and ex vivo HIV reactivation; Number of integrated HIV provirus copies in CD4+ T cells associated or not with platelets. Monitoring of the transcriptional competence of platelet-associated reservoirs ex vivo, and the capacity of platelets to reactivate these reservoirs (latency reversal) in vitro based on the following criterion: Frequency of J-Lat GFP+ cells (indicating a reactivated provirus in this reporter cell) after coculture with platelets obtained from individuals of the different experimental groups. |
at enrollment
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Olivier Robineau, MD, PhD, Centre Hospitalier de Tourcoing
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Blood-Borne Infections
- Urogenital Diseases
- Genital Diseases
- Immune System Diseases
- Infections
- RNA Virus Infections
- Virus Diseases
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Slow Virus Diseases
- HIV Infections
- Acquired Immunodeficiency Syndrome
- Investigative Techniques
- Specimen Handling
- Clinical Laboratory Techniques
- Diagnostic Techniques and Procedures
- Diagnosis
- Punctures
- Surgical Procedures, Operative
- Blood Specimen Collection
Other Study ID Numbers
- CHT/URC/2023/10
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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