Description

The VISCONTI study proposed that post-treatment control (PTC) of HIV infection might be favored by early antiretroviral treatment (ART) initiation. However, a formal demonstration has not been established and the underlying mechanisms leading to PTC remain elusive. The pVISCONTI program aims to assess, in standardized conditions, the impact of early versus late ART initiation on viral reservoirs and immune responses, and the outcome after analytical treatment interruption (ATI). Using the Cynomolgus Macaques model of SIVmac251 infection, the specific aims of this study are i)to dissect, at the systemic and tissue level, the  viral diversity, dissemination, replication and reservoir levels at treatment initiation, at the time of treatment interruption and post-interruption, ii)to evaluate how such treatments impact T cell reconstitution and turnover, ii)to identify anti-viral immune responses, both innate and adaptive, associated with transient or long-term control of infection after treatment interruption. To assess how early vs. delayed treatment impacts the priming, maturation and preservation of such responses, and iv) to discover (systemic) biomarkers predicting, at the time of treatment initiation or during treatment, the outcome of treatment interruption.

Country
France
Starting year
2016
Duration
7 years
Budget
5.2M€

Linked Publications

Expansion of Immature Neutrophils During SIV Infection Is Associated With Their Capacity to Modulate T-Cell Function

Lemaitre J, Desjardins D, Gallouët AS, Gomez-Pacheco M, Bourgeois C, Favier B, Sáez-Cirión A, Le Grand R, Lambotte O. Front Immunol. 2022 Feb 3;13:781356. doi: 10.3389/fimmu.2022.781356. PMID: 35185880 

CD32+CD4+ T Cells Sharing B Cell Properties Increase With Simian Immunodeficiency Virus Replication in Lymphoid Tissues

Huot N, Rascle P, Planchais C, Contreras V, Passaes C, Le Grand R, Beignon AS, Kornobis E, Legendre R, Varet H, Saez-Cirion A, Mouquet H, Jacquelin B, Müller-Trutwin M. Front Immunol. 2021 Jun 16;12:695148. doi: 10.3389/fimmu.2021.695148. PMID: 34220857 

Immunometabolism and HIV-1 pathogenesis: food for thought.

Sáez-Cirión A, Sereti I (2021). Nat Rev Immunol., 21(1):5-19. doi: 10.1038/s41577-020-0381-7.

SIV-induced terminally differentiated adaptive NK cells in lymph nodes associated with enhanced MHC-E restricted activity

Huot N, Rascle P, Petitdemange C, Contreras V, Stürzel CM, Baquero E, Harper JL, Passaes C, Legendre R, Varet H, Madec Y, Sauermann U, Stahl-Hennig C, Nattermann J, Saez-Cirion A, Le Grand R, Keith Reeves R, Paiardini M, Kirchhoff F, Jacquelin B, Müller-Trutwin M. Nat Commun. 2021 Feb 24;12(1):1282. doi: 10.1038/s41467-021-21402-1.PMID: 33627642

Role of NKG2a/c+ CD8 + T cells in pathogenic versus non-pathogenic SIV infections

Huot N, Rascle P, Tchitchek N, Wimmer B, Passaes C, Contreras V, Desjardins D, Stahl-Hennig C, Le Grand R, Saez-Cirion A, Jacquelin B, Müller-Trutwin M. iScience. 2021 Mar 15;24(4):102314. doi: 10.1016/j.isci.2021.102314. PMID: 33870131

Ultrasensitive Detection of p24 in Plasma Samples from People with Primary and Chronic HIV-1 Infection

Passaes C, Delagreverie HM, Avettand-Fenoel V, David A, Monceaux V, Essat A, Müller-Trutwin M, Duffy D, De Castro N, Wittkop L, Rouzioux C, Molina JM, Meyer L, Delaugerre C, Sáez-Cirión A. J Virol. 2021 Jun 24;95(14):e0001621. doi: 10.1128/JVI.00016-21. PMID: 33952636 

Optimal Maturation of the SIV-Specific CD8 + T Cell Response after Primary Infection Is Associated with Natural Control of SIV: ANRS SIC Study

Passaes C, Millet A, Madelain V, Monceaux V, David A, Versmisse P, Sylla N, Gostick E, Llewellyn-Lacey S, Price DA, Blancher A, Dereuddre-Bosquet N, Desjardins D, Pancino G, Le Grand R, Lambotte O, Müller-Trutwin M, Rouzioux C, Guedj J, Avettand-Fenoel V, Vaslin B, Sáez-Cirión A. Cell Rep. 2020 Sep 22;32(12):108174. doi: 10.1016/j.celrep.2020.108174. PMID: 32966788.

Modeling SIV kinetics supports that cytotoxic response drives natural control and unravels heterogeneous populations of infected cells

V. Madelain, C. Passaes, A. Millet, V. Avettand-Fenoel, R. Djidjou-Demasse, N. Dereuddre-Bosquet, R. Le Grand, C. Rouzioux, B. Vaslin, A. Saez-Cirion, J. Guedj. doi: https://doi.org/10.1101/2020.01.19.911594

Mass Cytometry Reveals the Immaturity of Circulating Neutrophils during SIV Infection

Lemaitre J, Cosma A, Desjardins D, Lambotte O, Le Grand R. J Innate Immun. 2020;12(2):170-181. doi: 10.1159/000499841. Epub 2019 Jun 21. PMID: 31230057; PMCID: PMC7103026.

Antiapoptotic Clone 11-Derived Peptides Induce In Vitro Death of CD4+ T Cells Susceptible to HIV-1 Infection

Mikhailova A, Valle-Casuso JC, David A, Monceaux V, Volant S, Passaes C, Elfidha A, Müller-Trutwin M, Poyet JL, Sáez-Cirión A. J Virol. 2020 Jul 1;94(14):e00611-20. doi: 10.1128/JVI.00611-20. PMID: 32350074 

Metabolic plasticity of HIV-specific CD8 + T cells is associated with enhanced antiviral potential and natural control of HIV-1 infection

Angin M, Volant S, Passaes C, Lecuroux C, Monceaux V, Dillies MA, Valle-Casuso JC, Pancino G, Vaslin B, Le Grand R, Weiss L, Goujard C, Meyer L, Boufassa F, Müller-Trutwin M, Lambotte O, Sáez-Cirión A. Nat Metab. 2019 Jul;1(7):704-716. doi: 10.1038/s42255-019-0081-4. Epub 2019 Jul 12. PMID: 32694646.

Ultrasensitive HIV-1 p24 Assay Detects Single Infected Cells and Differences in Reservoir Induction by Latency Reversal Agents

Passaes CPB, Bruel T, Decalf J, David A, Angin M, Monceaux V, Muller-Trutwin M, Noel N, Bourdic K, Lambotte O, Albert ML, Duffy D, Schwartz O, Sáez-Cirión A. J Virol. 2017 Feb 28;91(6):e02296-16. doi: 10.1128/JVI.02296-16. PMID: 28077644; PMCID: PMC5331803.

Funding Agencies