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

NCT05243381 | Unknown

• 1 other identifier: RECHMPL21_0518
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infections

Keywords

Immune non-responder HIV-patients; Immune responder HIV-patients; HIV-1 antisense protein; Exosomes; NK cells

Outcome Measures

Primary Outcomes (1)

• Immune status of HIV-infected patients

  CD4+ T-cell count

  The day of inclusion

Secondary Outcomes (4)

• HIV-1 Antisense protein

  The day of inclusion

• Impacts of exosomes on NK cell activity

  The day of inclusion

• NK cells phenotyping

  The day of inclusion

• NK cells functionality

  The day of inclusion

Study Arms (2)

Immune non-responder patients

OTHER

* 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

Immune responder patients

OTHER

* 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

Interventions

20 ml blood test BIOLOGICAL

20 ml blood test

Immune non-responder patients; Immune responder patients

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

La Colombiere Hospital

Montpellier, Herault, 34295, France

RECRUITING

Related Publications (14)

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  PMID: 17910760 BACKGROUND

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  PMID: 23035216 BACKGROUND

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MeSH Terms

Conditions

HIV Infections

Interventions

Hematologic Tests

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Alain MAKINSON, MH PD

  UH MONTPELLIER

  PRINCIPAL INVESTIGATOR

• Antoine GROSS, PHD

  Centre National de la Recherche Scientifique, France

  STUDY DIRECTOR

Central Study Contacts

Alain MAKINSON, MH PD

CONTACT

+33467339510; a-makinson@chu-montpellier.fr

Charlotte SILVESTRE, PharmD

CONTACT

+33434359441; charlotte.silvestre@irim.cnrs.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2022
• First Posted: February 17, 2022
• Study Start: April 22, 2022
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2024
• Last Updated: September 7, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)