HIV SeropositivityPLAQUEVIHNCT04062825
Interaction Between HIV and Platelets
An observational study of HIV Seropositivity, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The investigators propose that the lack of immune response in InR is driven by HIV-containing platelets that might interact with macrophages and CD4+ T-cells although by different mechanisms. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- HIV Seropositivity
- How many people
- 240 participants
- Where
- 1 siteFrance
- Study dates
- 17 Apr 2020to Mar 2025
- Phase
- Observational
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 200 VIH positive patients without lymphome + 20 VIH positive patients with lymphome + 20 healthy volunteers (VIH negative).
Who may be able to join
- For all patients:
- aged ⩾ 18 years;
- patients who can read and understand information document.
- For VIH positive patients without lymphoma:
- VIH positive patients with negative or positive viral load under cART since 1 year;
- patient under cART.
Show all 12Show fewer
- For VIH positive patients with lymphoma:
- VIH positive patient with negative viral load under cART since 1 year;
- patient with lymphoma.
- For Healthy Volunteers:
- VIH negative patient (control) already included in clinical trial;
- patient major without haematological pathology.
Who cannot join
- patient < 18 years;
- Unable to read and understand information document.
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Service Hématologie Immunologie, Hôpital Ambroise Paré
Boulogne-Billancourt, 92100
About this study
Official title: Interaction of HIV/Platelets and HIV-platelets/Lymphocytes in HIV Patients Under cART Treatment But Immunological Non Responders
The investigators propose that the lack of immune response in InR is driven by HIV-containing platelets that might interact with macrophages and CD4+ T-cells although by different mechanisms. In the one hand, HIV-sheltering platelets might fuel tissue HIV macrophage and in turn T cell reservoirs as observed in InRs and/or maintain a low-level viral replication in macrophages, sustaining a persistent inflammatory profile on in these cells. In the other hand,HIV-sheltering platelets might induce CD4+ T-cells dysfunctions via platelets/ectosomes, although without promoting platelet-to-T-cell HIV transfer/infection, thereby increasing the number of peripheral inflammatory TH17 cells and a TH17/Treg unbalance as observed in InRs.
Main Objectives:
- To characterize and the molecular and functional level the platelet factors implicated in HIV transfer to tissue-like macrophages as well as in the immunomodulatory activity of HIV-containing platelets on macrophages and CD4+ T-cells. ii) To interrogate the transfer of HIV-containing platelet-derived mRNA and microRNA to tissue-like macrophages and CD4+ T-cells as one major mechanism of target cell immunomodulation. iii) To investigate the therapeutic potential of anti-platelet aggregation/activation agents (e.g. Abciximab), known to block platelet-immune cell interaction, in improving immune cell functions in vitro and promoting immunological recovery in vivo.
Read the detailed description
The investigators have recently shown that infectious HIV is carried by platelets in the blood of HIV-infected patients which failed to respond immunologically to cART despite viral suppression (Immunological nonresponders, InRs) and that platelets can mediate HIV transmission to macrophages in vitro, in line with our recent description of HIV reservoir occurrence and establishment in macrophages in cART-suppressed patients. Around 20% of the overall cART-treated patients are InRs that fail to reconstitute their competent immune status despite treatment observance with prolonged viral suppression. The causes of this immunological failure remain unclear and no treatment is available to improve the health of InRs, which are at higher risk of AIDS and non-AIDS morbidity and mortality. The poor immunological recovery in InRs is mainly driven by a sustained low CD4+ T-cell counts that relies on persistent inflammation and immune activation affecting T-cell population profile.
Platelets are cleared by tissue macrophages in vivo in physiological or inflammatory contexts, what could represent a route for HIV to establish reservoirs in macrophages. We have shown that HIV sheltered in platelets can transfer infection to macrophages, in a process blocked by anti-αIIb/ β3 antibody Abciximab. This infection is productive as in turn, infection spreads replication-competent virus to non-infected CD4+ T-cells. This viral spread may increase the blood T-cell HIV reservoir, a hallmark of immunological failure as observed in InRs. In contrast, HIV-containing platelets fail to directly infect CD4+ T, unless infection is forced by the fusion inducer polybrene. Thus, in contrast to macrophages, CD4+ T cells are not targeted by HIV enclosed in platelets.
However, HIV-containing platelets might immunomodulate CD4+ T cell functions thereby triggering the immunological failure observed in cART-suppressed patients. Hence, platelet-T-cell conjugates form in the blood of HIV patients, suggesting that HIV-containing platelets could downregulate T-cell functions. Platelets are known to express adhesive proteins that not only promote platelet aggregation responsible for primary hemostasis, but also to mediate interactions with leukocytes, driving either inhibition of proliferation and differentiation of CD4+ T-cells into TH17, crucial in mediating chronic inflammation. Platelets can also shed microvesicles (ectosomes) which directly contact these lymphocytes, driving TH17 polarization of CD4+ T-cells and in turn an unbalanced TReg/TH17 ratio characteristic of InRs. Such TReg/TH17 unbalance might reflect a persistent inflammatory state that could translate in a cytotoxic/antiproliferative effect on CD4+ T-cells and ultimately immunological failure.
Very recently, we found that the number of platelets-CD4+ T-cells conjugates circulating in the blood of cART-treated HIV-infected patients is increased in InRs (virally suppressed and <350 CD4+T-cells/μl) compared with immunological responders (IR, >500 CD4+T-cells/μl). In addition, conjugates form more with TH17 in InR compared with IR, whereas conjugates form equally with TReg in the two InR and IR patients groups. These results indicate that InRs not only present a strong probability to have HIV-containing platelets but are also prone to form platelets-TH17 cells conjugates, suggesting a causal connection between association of HIV with platelets and platelet-driven immunomodulation of CD4+T-cells toward a TH17 profile. Whether these platelet-TH17 conjugates we observed form with full platelets or platelet ectosome (that both harbor CD41 used as platelet marker in our conjugate analyses) remains unknown.
Importantly, HIV RNA is only detected in circulating CD4+ T-cell reservoirs when latent proviral DNA is reactivated, suggesting that platelet-containing HIV does not conjugate with CD4+T cell in InR patients but rather with bystander platelets or platelet ectosomes (lacking HIV). Thus, immunomodulation of CD4+T cells in InRs might result from the interaction with these bystander platelet/ectosomes or ectosomes shed from HIV-containing platelets.
Platelets have been shown to exchange mRNA upon interaction with immune cells and tumors . Furthermore, transfer of functional mRNA and microRNA is so far demonstrated to be mediated by platelet ectosomes, targeting macrophage/monocytic and epithelial cells. Thus, transfer of messenger RNAs or microRNAs from platelets/ectosomes to macrophages and/or CD4+ T-cells could be the mechanism of platelet-dependent immunomodulation of target leukocytes. Platelets display a repertoire of mainly pro-inflammatory microRNAs such as miRNA-155 and miRNA-326, involved in NF-κB-mediated inflammatory macrophage responses 25 and TH17 cell-polarization. These miRNAs could be differentially expressed in platelets containing HIV and their eventual transfer to target immune cells could participate in immune cell dysfunction as observed in InRs. Furthermore, αIIb/ β3 mRNA are platelet-specific transcripts conserved in circulating platelets throughout their life-span, and can be exploited to tag leukocytes targeted by mRNA/microRNA of HIV-containing platelets.
- Conditions
- HIV Seropositivity
- Keywords
- HIV, platelets, lymphocytes, cART, InRs
- Medical subject headings
- HIV Seropositivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| VIH positive patients without lymphoma | 200 VIH positive patients without lymphoma | |
| VIH positive patients with lymphoma | 20 VIH positive patients with lymphoma | |
| healthy volunteers | 20 healthy volunteers |
What is being measured
The primary outcome is the main question the study is designed to answer.
CD4 number will be determined
Immunological response status based on the presence-absence of HIV in platelets during follow-up: CD4 number will be determined by flow cytometry.
Measured: at 48 month
VIH level in platelet will be quantified
Immunological response status based on the presence-absence of HIV in platelets during follow-up: VIH level in platelet will be quantified by flow fich and PCR.
Measured: at 48 month
Secondary outcomes (6)
potential interaction between platelets and lymphocytes
in vitro characterization of interaction between lymphocytes and platelets by microscopy. The cells will be stained with specific antibodies
Measured: 12-36 months
potential interaction between platelets and lymphocytes
in vitro characterization of interaction between lymphocytes and platelets by flow cytometry. The cells will be stained with specific antibodies
Measured: 12-36 months
analyze if the interaction can be blocked by anti GPIIbIIIa
anti GPIIbIIIa will be added in culture dish with platelets and lymphocytes. Analysis of inhibition of interaction will be performed by flow cytometry.
Measured: 12-36 months
analyze if the interaction can be blocked by anti GPIIbIIIa
anti GPIIbIIIa will be added in culture dish with platelets and lymphocytes. Analysis of inhibition of interaction will be performed by microscopy.
Measured: 12-36 months
HIV expression on bone marrow smear
cells from bone marrow will be spread on a slide; and presence of HIV will be performed with an anti HIV anti body
Measured: 1-48 months
soluble factors secretion
HIV+ platelets will be cultivated with donor's CD4 lymphocytes of. By ELISA and/or Bioplex, the secretion of soluble factors (cytokines, chemokines, soluble receptors), secreted by Lymphocytes in the culture medium will be studied.
Measured: 12-36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2019
- Study start17 Apr 2020
- Primary completionMar 2025 (estimated)
- Study completionMar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (31)Papers the sponsor has linked to this study.
- Other trials for HIV SeropositivityStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Claude Capron, MD, Principal investigator, Service Hématologie Immunologie, Hôpital Ambroise ParéMORGANE BOMSEL, MD, Study director, Unité CNRS UMR 8104, INSERM U1016, Laboratoire Entrée muqueuse du VIH et Immunité muqueuse, Département Infection, Immunité et Inflammation, Institut Cochin Université Paris Descartes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04062825
- Sponsor's protocol ID
- 19CCN-VIH-Plaquettes
- Acronym
- PLAQUEVIH
- Status last verified
- Mar 2023
- First submitted
- 1 Jul 2019
- Last updated
- 17 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ganor Y, Real F, Sennepin A, Dutertre CA, Prevedel L, Xu L, Tudor D, Charmeteau B, Couedel-Courteille A, Marion S, Zenak AR, Jourdain JP, Zhou Z, Schmitt A, Capron C, Eugenin EA, Cheynier R, Revol M, Cristofari S, Hosmalin A, Bomsel M. HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy. Nat Microbiol. 2019 Apr;4(4):633-644. doi: 10.1038/s41564-018-0335-z. Epub 2019 Feb 4.
PubMed 30718846Real F, Sennepin A, Ganor Y, Schmitt A, Bomsel M. Live Imaging of HIV-1 Transfer across T Cell Virological Synapse to Epithelial Cells that Promotes Stromal Macrophage Infection. Cell Rep. 2018 May 8;23(6):1794-1805. doi: 10.1016/j.celrep.2018.04.028.
PubMed 29742434Kaufmann GR, Perrin L, Pantaleo G, Opravil M, Furrer H, Telenti A, Hirschel B, Ledergerber B, Vernazza P, Bernasconi E, Rickenbach M, Egger M, Battegay M; Swiss HIV Cohort Study Group. CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med. 2003 Oct 13;163(18):2187-95. doi: 10.1001/archinte.163.18.2187.
PubMed 14557216Baker JV, Peng G, Rapkin J, Krason D, Reilly C, Cavert WP, Abrams DI, MacArthur RD, Henry K, Neaton JD; Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). Poor initial CD4+ recovery with antiretroviral therapy prolongs immune depletion and increases risk for AIDS and non-AIDS diseases. J Acquir Immune Defic Syndr. 2008 Aug 15;48(5):541-6. doi: 10.1097/QAI.0b013e31817bebb3.
PubMed 18645520Kelley CF, Kitchen CM, Hunt PW, Rodriguez B, Hecht FM, Kitahata M, Crane HM, Willig J, Mugavero M, Saag M, Martin JN, Deeks SG. Incomplete peripheral CD4+ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment. Clin Infect Dis. 2009 Mar 15;48(6):787-94. doi: 10.1086/597093.
PubMed 19193107Chene G, Sterne JA, May M, Costagliola D, Ledergerber B, Phillips AN, Dabis F, Lundgren J, D'Arminio Monforte A, de Wolf F, Hogg R, Reiss P, Justice A, Leport C, Staszewski S, Gill J, Fatkenheuer G, Egger ME; Antiretroviral Therapy Cohort Collaboration. Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies. Lancet. 2003 Aug 30;362(9385):679-86. doi: 10.1016/s0140-6736(03)14229-8.
PubMed 12957089Deeks SG, Kitchen CM, Liu L, Guo H, Gascon R, Narvaez AB, Hunt P, Martin JN, Kahn JO, Levy J, McGrath MS, Hecht FM. Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load. Blood. 2004 Aug 15;104(4):942-7. doi: 10.1182/blood-2003-09-3333. Epub 2004 Apr 29.
PubMed 15117761Hunt PW, Martin JN, Sinclair E, Bredt B, Hagos E, Lampiris H, Deeks SG. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis. 2003 May 15;187(10):1534-43. doi: 10.1086/374786. Epub 2003 Apr 23.
PubMed 12721933Marziali M, De Santis W, Carello R, Leti W, Esposito A, Isgro A, Fimiani C, Sirianni MC, Mezzaroma I, Aiuti F. T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART. AIDS. 2006 Oct 24;20(16):2033-41. doi: 10.1097/01.aids.0000247588.69438.fd.
PubMed 17053349Nunes-Alves C, Nobrega C, Behar SM, Correia-Neves M. Tolerance has its limits: how the thymus copes with infection. Trends Immunol. 2013 Oct;34(10):502-10. doi: 10.1016/j.it.2013.06.004. Epub 2013 Jul 16.
PubMed 23871487Wilson EM, Singh A, Hullsiek KH, Gibson D, Henry WK, Lichtenstein K, Onen NF, Kojic E, Patel P, Brooks JT, Sereti I, Baker JV; Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) Investigators. Monocyte-activation phenotypes are associated with biomarkers of inflammation and coagulation in chronic HIV infection. J Infect Dis. 2014 Nov 1;210(9):1396-406. doi: 10.1093/infdis/jiu275. Epub 2014 May 9.
PubMed 24813472Ballem PJ, Belzberg A, Devine DV, Lyster D, Spruston B, Chambers H, Doubroff P, Mikulash K. Kinetic studies of the mechanism of thrombocytopenia in patients with human immunodeficiency virus infection. N Engl J Med. 1992 Dec 17;327(25):1779-84. doi: 10.1056/NEJM199212173272503.
PubMed 1435932Grozovsky R, Hoffmeister KM, Falet H. Novel clearance mechanisms of platelets. Curr Opin Hematol. 2010 Nov;17(6):585-9. doi: 10.1097/MOH.0b013e32833e7561.
PubMed 20729731Hatano H, Hayes TL, Dahl V, Sinclair E, Lee TH, Hoh R, Lampiris H, Hunt PW, Palmer S, McCune JM, Martin JN, Busch MP, Shacklett BL, Deeks SG. A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response. J Infect Dis. 2011 Apr 1;203(7):960-8. doi: 10.1093/infdis/jiq138.
PubMed 21402547Green SA, Smith M, Hasley RB, Stephany D, Harned A, Nagashima K, Abdullah S, Pittaluga S, Imamichi T, Qin J, Rupert A, Ober A, Lane HC, Catalfamo M. Activated platelet-T-cell conjugates in peripheral blood of patients with HIV infection: coupling coagulation/inflammation and T cells. AIDS. 2015 Jul 17;29(11):1297-308. doi: 10.1097/QAD.0000000000000701.
PubMed 26002800
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interaction of HIV/Platelets and HIV-platelets/Lymphocytes in HIV Patients Under cART Treatment But Immunological Non Responders
- ClinicalTrials.gov ID
- NCT04062825
- Acronym / sponsor ID
- PLAQUEVIH / 19CCN-VIH-Plaquettes
- Conditions
- HIV Seropositivity
- Keywords
- HIV, platelets, lymphocytes, cART, InRs
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France
- Study start
- 17 Apr 2020 (actual)
- Primary completion
- Mar 2025 (estimated)
- Study completion
- Mar 2025 (estimated)
- First posted
- 20 Aug 2019 (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.
The investigators propose that the lack of immune response in InR is driven by HIV-containing platelets that might interact with macrophages and CD4+ T-cells although by different mechanisms. In the one hand, HIV-sheltering platelets might fuel tissue HIV macrophage and in turn T cell reservoirs as observed in InRs and/or maintain a low-level viral replication in macrophages, sustaining a persistent inflammatory profile on in these cells. In the other hand,HIV-sheltering platelets might induce CD4+ T-cells dysfunctions via platelets/ectosomes, although without promoting platelet-to-T-cell HIV transfer/infection, thereby increasing the number of peripheral inflammatory TH17 cells and a TH17/Treg unbalance as observed in InRs.
Main Objectives:
- To characterize and the molecular and functional level the platelet factors implicated in HIV transfer to tissue-like macrophages as well as in the immunomodulatory activity of HIV-containing platelets on macrophages and CD4+ T-cells. ii) To interrogate the transfer of HIV-containing platelet-derived mRNA and microRNA to tissue-like macrophages and CD4+ T-cells as one major mechanism of target cell immunomodulation. iii) To investigate the therapeutic potential of anti-platelet aggregation/activation agents (e.g. Abciximab), known to block platelet-immune cell interaction, in improving immune cell functions in vitro and promoting immunological recovery in vivo.
Detailed description
The investigators have recently shown that infectious HIV is carried by platelets in the blood of HIV-infected patients which failed to respond immunologically to cART despite viral suppression (Immunological nonresponders, InRs) and that platelets can mediate HIV transmission to macrophages in vitro, in line with our recent description of HIV reservoir occurrence and establishment in macrophages in cART-suppressed patients. Around 20% of the overall cART-treated patients are InRs that fail to reconstitute their competent immune status despite treatment observance with prolonged viral suppression. The causes of this immunological failure remain unclear and no treatment is available to improve the health of InRs, which are at higher risk of AIDS and non-AIDS morbidity and mortality. The poor immunological recovery in InRs is mainly driven by a sustained low CD4+ T-cell counts that relies on persistent inflammation and immune activation affecting T-cell population profile.
Platelets are cleared by tissue macrophages in vivo in physiological or inflammatory contexts, what could represent a route for HIV to establish reservoirs in macrophages. We have shown that HIV sheltered in platelets can transfer infection to macrophages, in a process blocked by anti-αIIb/ β3 antibody Abciximab. This infection is productive as in turn, infection spreads replication-competent virus to non-infected CD4+ T-cells. This viral spread may increase the blood T-cell HIV reservoir, a hallmark of immunological failure as observed in InRs. In contrast, HIV-containing platelets fail to directly infect CD4+ T, unless infection is forced by the fusion inducer polybrene. Thus, in contrast to macrophages, CD4+ T cells are not targeted by HIV enclosed in platelets.
However, HIV-containing platelets might immunomodulate CD4+ T cell functions thereby triggering the immunological failure observed in cART-suppressed patients. Hence, platelet-T-cell conjugates form in the blood of HIV patients, suggesting that HIV-containing platelets could downregulate T-cell functions. Platelets are known to express adhesive proteins that not only promote platelet aggregation responsible for primary hemostasis, but also to mediate interactions with leukocytes, driving either inhibition of proliferation and differentiation of CD4+ T-cells into TH17, crucial in mediating chronic inflammation. Platelets can also shed microvesicles (ectosomes) which directly contact these lymphocytes, driving TH17 polarization of CD4+ T-cells and in turn an unbalanced TReg/TH17 ratio characteristic of InRs. Such TReg/TH17 unbalance might reflect a persistent inflammatory state that could translate in a cytotoxic/antiproliferative effect on CD4+ T-cells and ultimately immunological failure.
Very recently, we found that the number of platelets-CD4+ T-cells conjugates circulating in the blood of cART-treated HIV-infected patients is increased in InRs (virally suppressed and <350 CD4+T-cells/μl) compared with immunological responders (IR, >500 CD4+T-cells/μl). In addition, conjugates form more with TH17 in InR compared with IR, whereas conjugates form equally with TReg in the two InR and IR patients groups. These results indicate that InRs not only present a strong probability to have HIV-containing platelets but are also prone to form platelets-TH17 cells conjugates, suggesting a causal connection between association of HIV with platelets and platelet-driven immunomodulation of CD4+T-cells toward a TH17 profile. Whether these platelet-TH17 conjugates we observed form with full platelets or platelet ectosome (that both harbor CD41 used as platelet marker in our conjugate analyses) remains unknown.
Importantly, HIV RNA is only detected in circulating CD4+ T-cell reservoirs when latent proviral DNA is reactivated, suggesting that platelet-containing HIV does not conjugate with CD4+T cell in InR patients but rather with bystander platelets or platelet ectosomes (lacking HIV). Thus, immunomodulation of CD4+T cells in InRs might result from the interaction with these bystander platelet/ectosomes or ectosomes shed from HIV-containing platelets.
Platelets have been shown to exchange mRNA upon interaction with immune cells and tumors . Furthermore, transfer of functional mRNA and microRNA is so far demonstrated to be mediated by platelet ectosomes, targeting macrophage/monocytic and epithelial cells. Thus, transfer of messenger RNAs or microRNAs from platelets/ectosomes to macrophages and/or CD4+ T-cells could be the mechanism of platelet-dependent immunomodulation of target leukocytes. Platelets display a repertoire of mainly pro-inflammatory microRNAs such as miRNA-155 and miRNA-326, involved in NF-κB-mediated inflammatory macrophage responses 25 and TH17 cell-polarization. These miRNAs could be differentially expressed in platelets containing HIV and their eventual transfer to target immune cells could participate in immune cell dysfunction as observed in InRs. Furthermore, αIIb/ β3 mRNA are platelet-specific transcripts conserved in circulating platelets throughout their life-span, and can be exploited to tag leukocytes targeted by mRNA/microRNA of HIV-containing platelets.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| VIH positive patients without lymphoma | – | –200 VIH positive patients without lymphoma |
| VIH positive patients with lymphoma | – | –20 VIH positive patients with lymphoma |
| healthy volunteers | – | –20 healthy volunteers |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 200 VIH positive patients without lymphome + 20 VIH positive patients with lymphome + 20 healthy volunteers (VIH negative).
Key inclusion criteria (12 listed)
- aged ⩾ 18 years;
- patients who can read and understand information document.
- VIH positive patients with negative or positive viral load under cART since 1 year;
- patient under cART.
- VIH positive patient with negative viral load under cART since 1 year;
Key exclusion criteria (2 listed)
- patient < 18 years;
- Unable to read and understand information document.
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
CD4 number will be determined
Time frame: at 48 month
Immunological response status based on the presence-absence of HIV in platelets during follow-up: CD4 number will be determined by flow cytometry.
VIH level in platelet will be quantified
Time frame: at 48 month
Immunological response status based on the presence-absence of HIV in platelets during follow-up: VIH level in platelet will be quantified by flow fich and PCR.
6 secondary outcomes
potential interaction between platelets and lymphocytes
Time frame: 12-36 months
potential interaction between platelets and lymphocytes
Time frame: 12-36 months
analyze if the interaction can be blocked by anti GPIIbIIIa
Time frame: 12-36 months
analyze if the interaction can be blocked by anti GPIIbIIIa
Time frame: 12-36 months
HIV expression on bone marrow smear
Time frame: 1-48 months
soluble factors secretion
Time frame: 12-36 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2023.
- Background: PubMed 30718846Ganor Y, Real F, Sennepin A, Dutertre CA, Prevedel L, Xu L, Tudor D, Charmeteau B, Couedel-Courteille A, Marion S, Zenak AR, Jourdain JP, Zhou Z, Schmitt A, Capron C, Eugenin EA, Cheynier R, Revol M, Cristofari S, Hosmalin A, Bomsel M. HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy. Nat Microbiol. 2019 Apr;4(4):633-644. doi: 10.1038/s41564-018-0335-z. Epub 2019 Feb 4.
- Background: PubMed 29742434Real F, Sennepin A, Ganor Y, Schmitt A, Bomsel M. Live Imaging of HIV-1 Transfer across T Cell Virological Synapse to Epithelial Cells that Promotes Stromal Macrophage Infection. Cell Rep. 2018 May 8;23(6):1794-1805. doi: 10.1016/j.celrep.2018.04.028.
- Background: PubMed 14557216Kaufmann GR, Perrin L, Pantaleo G, Opravil M, Furrer H, Telenti A, Hirschel B, Ledergerber B, Vernazza P, Bernasconi E, Rickenbach M, Egger M, Battegay M; Swiss HIV Cohort Study Group. CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med. 2003 Oct 13;163(18):2187-95. doi: 10.1001/archinte.163.18.2187.
- Background: PubMed 18645520Baker JV, Peng G, Rapkin J, Krason D, Reilly C, Cavert WP, Abrams DI, MacArthur RD, Henry K, Neaton JD; Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). Poor initial CD4+ recovery with antiretroviral therapy prolongs immune depletion and increases risk for AIDS and non-AIDS diseases. J Acquir Immune Defic Syndr. 2008 Aug 15;48(5):541-6. doi: 10.1097/QAI.0b013e31817bebb3.
- Background: PubMed 19193107Kelley CF, Kitchen CM, Hunt PW, Rodriguez B, Hecht FM, Kitahata M, Crane HM, Willig J, Mugavero M, Saag M, Martin JN, Deeks SG. Incomplete peripheral CD4+ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment. Clin Infect Dis. 2009 Mar 15;48(6):787-94. doi: 10.1086/597093.
- Background: PubMed 12957089Chene G, Sterne JA, May M, Costagliola D, Ledergerber B, Phillips AN, Dabis F, Lundgren J, D'Arminio Monforte A, de Wolf F, Hogg R, Reiss P, Justice A, Leport C, Staszewski S, Gill J, Fatkenheuer G, Egger ME; Antiretroviral Therapy Cohort Collaboration. Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies. Lancet. 2003 Aug 30;362(9385):679-86. doi: 10.1016/s0140-6736(03)14229-8.
- Background: PubMed 15117761Deeks SG, Kitchen CM, Liu L, Guo H, Gascon R, Narvaez AB, Hunt P, Martin JN, Kahn JO, Levy J, McGrath MS, Hecht FM. Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load. Blood. 2004 Aug 15;104(4):942-7. doi: 10.1182/blood-2003-09-3333. Epub 2004 Apr 29.
- Background: PubMed 12721933Hunt PW, Martin JN, Sinclair E, Bredt B, Hagos E, Lampiris H, Deeks SG. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis. 2003 May 15;187(10):1534-43. doi: 10.1086/374786. Epub 2003 Apr 23.
- Background: PubMed 17053349Marziali M, De Santis W, Carello R, Leti W, Esposito A, Isgro A, Fimiani C, Sirianni MC, Mezzaroma I, Aiuti F. T-cell homeostasis alteration in HIV-1 infected subjects with low CD4 T-cell count despite undetectable virus load during HAART. AIDS. 2006 Oct 24;20(16):2033-41. doi: 10.1097/01.aids.0000247588.69438.fd.
- Background: PubMed 23871487Nunes-Alves C, Nobrega C, Behar SM, Correia-Neves M. Tolerance has its limits: how the thymus copes with infection. Trends Immunol. 2013 Oct;34(10):502-10. doi: 10.1016/j.it.2013.06.004. Epub 2013 Jul 16.
- Background: PubMed 24813472Wilson EM, Singh A, Hullsiek KH, Gibson D, Henry WK, Lichtenstein K, Onen NF, Kojic E, Patel P, Brooks JT, Sereti I, Baker JV; Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) Investigators. Monocyte-activation phenotypes are associated with biomarkers of inflammation and coagulation in chronic HIV infection. J Infect Dis. 2014 Nov 1;210(9):1396-406. doi: 10.1093/infdis/jiu275. Epub 2014 May 9.
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- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Claude Capron, MD principal investigator
Service Hématologie Immunologie, Hôpital Ambroise Paré
MORGANE BOMSEL, MD study director
Unité CNRS UMR 8104, INSERM U1016, Laboratoire Entrée muqueuse du VIH et Immunité muqueuse, Département Infection, Immunité et Inflammation, Institut Cochin Université Paris Descartes
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 Seropositivity, run by Assistance Publique - Hôpitaux de Paris 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 12 inclusion and 2 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 17 Mar 2023. 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 Claude Capron, MD (+33(0)149095847, claude.capron@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CD4 number will be determined (time frame: at 48 month). The study lists 2 primary outcomes in all. 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 NCT04062825, which also lists 31 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 17 Mar 2023.