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HIV InfectionsINKASENCT05243381

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

A study testing 20 ml blood test in people with HIV Infections, run by University Hospital, Montpellier at 1 site in France.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 45 years and older
Conditions the study is for
HIV Infections
What is being tested?
20 ml blood test
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteFrance
Study dates
22 Apr 2022to Apr 2024
Phase
Interventional
Are there results?
None posted in the registry

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 45 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Alain MAKINSON, MH PD contact

+33467339510

a-makinson@chu-montpellier.fr

Charlotte SILVESTRE, PharmD contact

+33434359441

charlotte.silvestre@irim.cnrs.fr

France1 site, 1 recruiting
  • La Colombiere Hospital

    Montpellier, Herault, 34295

    Charlotte SILVESTRE, PharmD, +33434359441, charlotte.silvestre@irim.cnrs.fr

    Recruiting

Other trials in France

About this study

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.

Read more

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.

Read the 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).

Conditions
HIV Infections
Being tested
20 ml blood test
Keywords
Immune non-responder HIV-patients, Immune responder HIV-patients, HIV-1 antisense protein, Exosomes, NK cells
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 20 ml blood testBiological

    20 ml blood test

Study groups in NCT05243381
Study groupRoleWhat they receive
Immune non-responder patientsOther* HIV viral load < 50 copies/ml in the past 2 years * CD4+ T-cell count < 350 cells/mm3 on the last two tests
Receives: Biological: 20 ml blood test
Immune responder patientsOther* HIV viral load < 50 copies/ml in the past 2 years * CD4+ T-cell count > 500 cells/mm3 on the last two tests
Receives: Biological: 20 ml blood test

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Immune status of HIV-infected patients

    CD4+ T-cell count

    Measured: The day of inclusion

Secondary outcomes (4)
  1. HIV-1 Antisense protein

    HIV-1 antisense protein expression level

    Measured: The day of inclusion

  2. Impacts of exosomes on NK cell activity

    Cytotoxicity activity and cytokines production (intracellular staining and qRT-PCR) during cytotoxicity assay

    Measured: The day of inclusion

  3. NK cells phenotyping

    Flow cytometry phenotyping: subpopulation, activation and exhaustion markers

    Measured: The day of inclusion

  4. NK cells functionality

    Natural and antibody-dependent cytotoxicity assays

    Measured: The day of inclusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2022
  2. Study start22 Apr 2022
  3. Primary completionApr 2023 (estimated)
  4. Study completionApr 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05243381
Sponsor's protocol ID
RECHMPL21_0518
Acronym
INKASE
Status last verified
Sep 2022
First submitted
24 Jan 2022
Last updated
7 Sep 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Landry S, Halin M, Lefort S, Audet B, Vaquero C, Mesnard JM, Barbeau B. Detection, characterization and regulation of antisense transcripts in HIV-1. Retrovirology. 2007 Oct 2;4:71. doi: 10.1186/1742-4690-4-71.

    PubMed 17910760
  • Laverdure S, Gross A, Arpin-Andre C, Clerc I, Beaumelle B, Barbeau B, Mesnard JM. HIV-1 antisense transcription is preferentially activated in primary monocyte-derived cells. J Virol. 2012 Dec;86(24):13785-9. doi: 10.1128/JVI.01723-12. Epub 2012 Oct 3.

    PubMed 23035216
  • Bet A, Maze EA, Bansal A, Sterrett S, Gross A, Graff-Dubois S, Samri A, Guihot A, Katlama C, Theodorou I, Mesnard JM, Moris A, Goepfert PA, Cardinaud S. The HIV-1 antisense protein (ASP) induces CD8 T cell responses during chronic infection. Retrovirology. 2015 Feb 10;12:15. doi: 10.1186/s12977-015-0135-y.

    PubMed 25809376
  • Savoret J, Chazal N, Moles JP, Tuaillon E, Boufassa F, Meyer L, Lecuroux C, Lambotte O, Van De Perre P, Mesnard JM, Gross A. A Pilot Study of the Humoral Response Against the AntiSense Protein (ASP) in HIV-1-Infected Patients. Front Microbiol. 2020 Jan 24;11:20. doi: 10.3389/fmicb.2020.00020. eCollection 2020.

    PubMed 32117090
  • Cassan E, Arigon-Chifolleau AM, Mesnard JM, Gross A, Gascuel O. Concomitant emergence of the antisense protein gene of HIV-1 and of the pandemic. Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):11537-11542. doi: 10.1073/pnas.1605739113. Epub 2016 Sep 28.

    PubMed 27681623
  • Wang Y, Lifshitz L, Gellatly K, Vinton CL, Busman-Sahay K, McCauley S, Vangala P, Kim K, Derr A, Jaiswal S, Kucukural A, McDonel P, Hunt PW, Greenough T, Houghton J, Somsouk M, Estes JD, Brenchley JM, Garber M, Deeks SG, Luban J. HIV-1-induced cytokines deplete homeostatic innate lymphoid cells and expand TCF7-dependent memory NK cells. Nat Immunol. 2020 Mar;21(3):274-286. doi: 10.1038/s41590-020-0593-9. Epub 2020 Feb 17.

    PubMed 32066947
  • Giuliani E, Vassena L, Di Cesare S, Malagnino V, Desimio MG, Andreoni M, Barnaba V, Doria M. NK cells of HIV-1-infected patients with poor CD4+ T-cell reconstitution despite suppressive HAART show reduced IFN-gamma production and high frequency of autoreactive CD56bright cells. Immunol Lett. 2017 Oct;190:185-193. doi: 10.1016/j.imlet.2017.08.014. Epub 2017 Aug 19.

    PubMed 28826739
  • Florez-Alvarez L, Hernandez JC, Zapata W. NK Cells in HIV-1 Infection: From Basic Science to Vaccine Strategies. Front Immunol. 2018 Oct 17;9:2290. doi: 10.3389/fimmu.2018.02290. eCollection 2018.

    PubMed 30386329
  • Lucar O, Reeves RK, Jost S. A Natural Impact: NK Cells at the Intersection of Cancer and HIV Disease. Front Immunol. 2019 Aug 14;10:1850. doi: 10.3389/fimmu.2019.01850. eCollection 2019.

    PubMed 31474977
  • Perez PS, Romaniuk MA, Duette GA, Zhao Z, Huang Y, Martin-Jaular L, Witwer KW, Thery C, Ostrowski M. Extracellular vesicles and chronic inflammation during HIV infection. J Extracell Vesicles. 2019 Nov 6;8(1):1687275. doi: 10.1080/20013078.2019.1687275. eCollection 2019.

    PubMed 31998449
  • Pantazis N, Papastamopoulos V, Paparizos V, Metallidis S, Adamis G, Antoniadou A, Psichogiou M, Chini M, Sambatakou H, Sipsas NV, Gogos C, Chrysos G, Panagopoulos P, Katsarou O, Gikas A, Touloumi G; AMACS. Long-term evolution of CD4+ cell count in patients under combined antiretroviral therapy. AIDS. 2019 Aug 1;33(10):1645-1655. doi: 10.1097/QAD.0000000000002248.

    PubMed 31305332
  • Gras L, May M, Ryder LP, Trickey A, Helleberg M, Obel N, Thiebaut R, Guest J, Gill J, Crane H, Dias Lima V, d'Arminio Monforte A, Sterling TR, Miro J, Moreno S, Stephan C, Smith C, Tate J, Shepherd L, Saag M, Rieger A, Gillor D, Cavassini M, Montero M, Ingle SM, Reiss P, Costagliola D, Wit FWNM, Sterne J, de Wolf F, Geskus R; Antiretroviral Therapy Cohort Collaboration (ART-CC). Determinants of Restoration of CD4 and CD8 Cell Counts and Their Ratio in HIV-1-Positive Individuals With Sustained Virological Suppression on Antiretroviral Therapy. J Acquir Immune Defic Syndr. 2019 Mar 1;80(3):292-300. doi: 10.1097/QAI.0000000000001913.

    PubMed 30531492
  • Roul H, Mary-Krause M, Ghosn J, Delaugerre C, Pialoux G, Cuzin L, Launay O, Lacombe JM, Menard A, De Truchis P, Delfraissy JF, Weiss L, Costagliola D; FHDH-ANRS CO4. CD4+ cell count recovery after combined antiretroviral therapy in the modern combined antiretroviral therapy era. AIDS. 2018 Nov 13;32(17):2605-2614. doi: 10.1097/QAD.0000000000002010.

    PubMed 30289817
  • Mussini C, Lorenzini P, Cozzi-Lepri A, Lapadula G, Marchetti G, Nicastri E, Cingolani A, Lichtner M, Antinori A, Gori A, d'Arminio Monforte A; Icona Foundation Study Group. CD4/CD8 ratio normalisation and non-AIDS-related events in individuals with HIV who achieve viral load suppression with antiretroviral therapy: an observational cohort study. Lancet HIV. 2015 Mar;2(3):e98-106. doi: 10.1016/S2352-3018(15)00006-5. Epub 2015 Feb 6.

    PubMed 26424550
  • Silvestre C, Tuaillon E, Duroyon MM, Abrantes M, Thibout JC, Villalba M, Picot MC, Gross A, Makinson A. NK Count and Natural Cytotoxicity in Immune Nonresponders Versus Responders Living With HIV. J Med Virol. 2025 Feb;97(2):e70170. doi: 10.1002/jmv.70170.

    PubMed 39868926

Questions about this trial

What is this clinical trial studying?

A study testing 20 ml blood test in people with HIV Infections, run by University Hospital, Montpellier at 1 site in France.

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 5 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 7 Sep 2022. 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 France. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Alain MAKINSON, MH PD (+33467339510, a-makinson@chu-montpellier.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Immune status of HIV-infected patients (time frame: The day of inclusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05243381, which also lists 15 linked publications.

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 7 Sep 2022.

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