Limited HIV-1 Reactivation in Resting CD4+ T cells from Aviremic Patients under Protease Inhibitors

被引:11
|
作者
Kumar, Amit [1 ]
Abbas, Wasim [1 ]
Bouchat, Sophie [2 ]
Gatot, Jean-Stephane [2 ,4 ]
Pasquereau, Sebastien [1 ]
Kabeya, Kabamba [3 ]
Clumeck, Nathan [3 ]
De Wit, Stephane [3 ]
Van Lint, Carine [2 ]
Herbein, Georges [1 ]
机构
[1] Univ Franche Comte, CHRU Besancon, COMUE Bourgogne,SFR FED 4234, Dept Virol,Pathogens & Inflammat Lab,UPRES EA4266, F-25030 Besancon, France
[2] Univ Libre Bruxelles, IBMM, Lab Mol Virol, Gosselies, Belgium
[3] ULB, CHU St Pierre, Dept Infect Dis, Brussels, Belgium
[4] Domaine Univ Sart Tilman, CHU Liege, Serv Genet, B23, B-4000 Liege, Belgium
来源
SCIENTIFIC REPORTS | 2016年 / 6卷
关键词
RALTEGRAVIR INTENSIFICATION; INTEGRATION; INFECTION; LATENCY; REPLICATION; ACTIVATION; RECOVERY; INCREASE; VIREMIA; LEVEL;
D O I
10.1038/srep38313
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A latent viral reservoir that resides in resting CD4(+) T cells represents a major barrier for eradication of HIV infection. We test here the impact of HIV protease inhibitor (PI) based combination anti-retroviral therapy (cART) over nonnucleoside reverse transcriptase inhibitor (NNRTI)-based cART on HIV-1 reactivation and integration in resting CD4(+) T cells. This is a prospective cohort study of patients with chronic HIV-1 infection treated with conventional cART with an undetectable viremia. We performed a seven-year study of 47 patients with chronic HIV-infection treated with cART regimens and with undetectable plasma HIV-1 RNA levels for at least 1 year. Of these 47 patients treated with cART, 24 were treated with a PI-based regimen and 23 with a NNRTI-based regimen as their most recent treatment for more than one year. We evaluated the HIV-1 reservoir using reactivation assay and integrated HIV-1 DNA, respectively, in resting CD4(+) T cells. Resting CD4(+) T cells isolated from PI-treated patients compared to NNRTI-treated patients showed a limited HIV-1 reactivation upon T-cell stimulation (p = 0.024) and a lower level of HIV-1 integration (p = 0.024). Our study indicates that PI-based cART could be more efficient than NNRTI-based cART for limiting HIV-1 reactivation in aviremic chronically infected patients.
引用
收藏
页数:7
相关论文
共 50 条
  • [21] Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers
    Saez-Cirion, Asier
    Hamimi, Chiraz
    Bergamaschi, Anna
    David, Annie
    Versmisse, Pierre
    Melard, Adeline
    Boufassa, Faroudy
    Barre-Sinoussi, Francoise
    Lambotte, Olivier
    Rouzioux, Christine
    Pancino, Gianfranco
    BLOOD, 2011, 118 (04) : 955 - 964
  • [22] Nonnucleoside Reverse Transcriptase Inhibitors Reduce HIV-1 Production from Latently Infected Resting CD4+ T Cells following Latency Reversal
    Zerbato, Jennifer M.
    Tachedjian, Gilda
    Sluis-Cremer, Nicolas
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2017, 61 (03)
  • [23] SAMHD1 Impairs HIV-1 Gene Expression and Negatively Modulates Reactivation of Viral Latency in CD4+ T Cells
    Antonucci, Jenna M.
    Kim, Sun Hee
    St Gelais, Corine
    Bonifati, Serena
    Li, Tai-Wei
    Buzovetsky, Olga
    Knecht, Kirsten M.
    Duchon, Alice A.
    Xiong, Yong
    Musier-Forsyth, Karin
    Wu, Li
    JOURNAL OF VIROLOGY, 2018, 92 (15)
  • [24] Highly Efficient Autologous HIV-1 Isolation by Coculturing Macrophage With Enriched CD4+ T Cells From HIV-1 Patients
    Xufre, Cristina
    Gonzalez, Tania
    Leal, Lorna
    Trubey, Charles M.
    Lifson, Jeffrey D.
    Gatell, Jose Maria
    Alcami, Jose
    Climent, Nuria
    Garcia, Felipe
    Sanchez-Palomino, Sonsoles
    FRONTIERS IN VIROLOGY, 2022, 2
  • [25] Modest de novo Reactivation of Single HIV-1 Proviruses in Peripheral CD4+ T Cells by Romidepsin
    Kjaer, Kathrine
    Leth, Steffen
    Konrad, Christina V.
    Gunst, Jesper D.
    Nymann, Rasmus
    Ostergaard, Lars
    Sogaard, Ole S.
    Schleimann, Mariane H.
    Tolstrup, Martin
    Denton, Paul W.
    FRONTIERS IN VIROLOGY, 2021, 1
  • [26] Latent HIV-1 Infection of Resting CD4+ T Cells in the Humanized Rag2-/- γc-/- Mouse
    Choudhary, Shailesh K.
    Archin, Nancie M.
    Cheema, Manzoor
    Dahl, Noelle P.
    Garcia, J. Victor
    Margolis, David M.
    JOURNAL OF VIROLOGY, 2012, 86 (01) : 114 - 120
  • [27] Primary CD8+ T cells from elite suppressors effectively eliminate non-productively HIV-1 infected resting and activated CD4+ T cells
    Buckheit, Robert W., III
    Siliciano, Robert F.
    Blankson, Joel N.
    RETROVIROLOGY, 2013, 10
  • [28] Endothelial Cell Stimulation Overcomes Restriction and Promotes Productive and Latent HIV-1 Infection of Resting CD4+ T Cells
    Shen, Anding
    Baker, Jacob J.
    Scott, Geoffrey L.
    Davis, Yelena P.
    Ho, Yen-Yi
    Siliciano, Robert F.
    JOURNAL OF VIROLOGY, 2013, 87 (17) : 9768 - 9779
  • [29] Establishment of HIV-1 latency in resting CD4+ T cells depends on chemokine-induced changes in the actin cytoskeleton
    Cameron, Paul U.
    Saleh, Suha
    Sallmann, Georgina
    Solomon, Ajantha
    Wightman, Fiona
    Evans, Vanessa A.
    Boucher, Genevieve
    Haddad, Elias K.
    Sekaly, Rafick-Pierre
    Harman, Andrew N.
    Anderson, Jenny L.
    Jones, Kate L.
    Mak, Johnson
    Cunningham, Anthony L.
    Jaworowski, Anthony
    Lewin, Sharon R.
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (39) : 16934 - 16939
  • [30] Membrane metalloprotease TRABD2A restricts HIV-1 progeny production in resting CD4+ T cells by degrading viral Gag polyprotein
    Liang, Guoxin
    Zhao, Li
    Qiao, Ying
    Geng, Wenqing
    Zhang, Xiaowei
    Liu, Mei
    Dong, Jinxiu
    Ding, Haibo
    Sun, Hong
    Shang, Hong
    NATURE IMMUNOLOGY, 2019, 20 (06) : 711 - +