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Inflammation, NK Cells, Antisense Protein and Exosomes, and Correlation With Immune Response During HIV Infection (INKASE)

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ClinicalTrials.gov Identifier: NCT05243381
Recruitment Status : Recruiting
First Posted : February 17, 2022
Last Update Posted : September 7, 2022
Information provided by (Responsible Party):
University Hospital, Montpellier

Brief Summary:

More than 90% of HIV-infected patients on antiretroviral therapy have an undetectable viral load. However, approximately 15% of these individuals do not sufficiently restore their TCD4 lymphocytes and have an unfavorable CD4/CD8 ratio despite good adherence and an undetectable viral load. Factors associated with immunovirological discordance include low CD4 cell counts prior to antiretroviral therapy, low CD4/CD8 ratios and positive cytomegalovirus (CMV) serology. These patients are at risk of significant non-AIDS events and mortality.

The anti-sense protein (ASP) is synthesized from the anti-sense strand of HIV-1. A cytotoxic anti-ASP response of CD8 T lymphocytes and anti-ASP antibodies have been demonstrated in infected patients. The conservation of the ASP gene in HIV-1, the virus responsible for the pandemic, suggests that its maintenance confers an advantage to the virus. ASP induces an inflammatory phenotype in surrounding cells. ASP can be externalized by the cell through its interaction with its cellular partner Bat-3. Once externalized in soluble or exosomal form, Bat-3 has the ability to regulate NK cell activity. During HIV infection, NK functions are disrupted, including those related to the expression of the Bat-3 receptor, NKp30.

In patients, the inflammatory phenomenon is strongly associated with chronic HIV-1 infection. The efficacy of antiviral treatments does not allow a complete normalization of either the immune system function or the inflammatory status of the patient. The observed effect of ASP on inflammation raises the question of the involvement of ASP in the maintenance of a chronic inflammatory state in patients under treatment. Increased inflammation has also been associated in HIV-infected patients with elevated plasma exosome levels. In patients undergoing treatment, chronic inflammation remains a major problem and an important source of comorbidities (cardiovascular in particular) and probably contributes to the immunovirological non-response in immunodiscordant HIV-infected patients.

It is hypothesized that ASP bound to its cellular partner Bat-3 in exosomes would disrupt the cytotoxic activity of NK cells, sustain inflammation and have a deleterious effect on immune reconstitution.

Condition or disease Intervention/treatment Phase
HIV Infections Biological: 20 ml blood test Not Applicable

Detailed Description:

The main objective of the project is to characterize the presence of ex vivo NK cell perturbations in patients living with HIV (PLHIV) with immunovirological discordance, in relation to ASP expression and plasmatic exosomes. The secondary objectives will be to identify new biological parameters to study and to establish mechanistic hypothesis explaining the results obtained during the study.

The study has a pathophysiological aim and is approved by the committee for the protection of individuals. Two groups of patients will be constituted: one group of PLWHIV with immunovirological discordance (20 patients) and the other group of PLWHIV with a good immune reconstitution (40 patients).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Inflammation, NK Cells, Antisense Protein and Exosomes, and Correlation With Immune Response During HIV Infection
Actual Study Start Date : April 22, 2022
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Immune non-responder patients
  • HIV viral load < 50 copies/ml in the past 2 years
  • CD4+ T-cell count < 350 cells/mm3 on the last two tests
Biological: 20 ml blood test
20 ml blood test

Immune responder patients
  • HIV viral load < 50 copies/ml in the past 2 years
  • CD4+ T-cell count > 500 cells/mm3 on the last two tests
Biological: 20 ml blood test
20 ml blood test

Primary Outcome Measures :
  1. Immune status of HIV-infected patients [ Time Frame: The day of inclusion ]
    CD4+ T-cell count

Secondary Outcome Measures :
  1. HIV-1 Antisense protein [ Time Frame: The day of inclusion ]
    HIV-1 antisense protein expression level

  2. Impacts of exosomes on NK cell activity [ Time Frame: The day of inclusion ]
    Cytotoxicity activity and cytokines production (intracellular staining and qRT-PCR) during cytotoxicity assay

  3. NK cells phenotyping [ Time Frame: The day of inclusion ]
    Flow cytometry phenotyping: subpopulation, activation and exhaustion markers

  4. NK cells functionality [ Time Frame: The day of inclusion ]
    Natural and antibody-dependent cytotoxicity assays

Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patiens living with HIV over 45 years old
  • At least 2 measurements of CD4+ T-cell and HIV viral load in the last 2 years
  • HIV viral load < 50 copies/ml in the past 2 years
  • For the immune non-responder patients : CD4+ T-cell count < 350 cells/mm3 on the last two tests
  • For the immune responder patients: CD4+ T-cell count > 500 cells/mm3 on the last two tests

Exclusion Criteria:

  • No antiretroviral treatment
  • Immunosuppressive treatment
  • History of cancer less than 5 years
  • Pregnancy
  • Breastfeeding mother
  • Adult protected by law or patient under guardianship or curatorship
  • Failure to obtain written informed consent after a reflection period
  • Not be affiliated to a French social security system or a beneficiary of such a system

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): NCT05243381

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Contact: Alain MAKINSON, MH PD +33467339510 a-makinson@chu-montpellier.fr
Contact: Charlotte SILVESTRE, PharmD +33434359441 charlotte.silvestre@irim.cnrs.fr

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La Colombiere Hospital Recruiting
Montpellier, Herault, France, 34295
Contact: Charlotte SILVESTRE, PharmD    +33434359441    charlotte.silvestre@irim.cnrs.fr   
Sponsors and Collaborators
University Hospital, Montpellier
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Principal Investigator: Alain MAKINSON, MH PD UH MONTPELLIER
Study Director: Antoine GROSS, PHD Centre National de la Recherche Scientifique, France

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Responsible Party: University Hospital, Montpellier
ClinicalTrials.gov Identifier: NCT05243381    
Other Study ID Numbers: RECHMPL21_0518
First Posted: February 17, 2022    Key Record Dates
Last Update Posted: September 7, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 University Hospital, Montpellier:
Immune non-responder HIV-patients
Immune responder HIV-patients
HIV-1 antisense protein
NK cells
Additional relevant MeSH terms:
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Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Disease Attributes
Pathologic Processes
Blood-Borne Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases