The Effect of Arsenic Trioxide on Eliminating HIV-1 Reservoir Combined With cART

Summary

To evaluate the safety and efficacy of arsenic trioxide combined with cART in eliminating latent HIV-1 reservoir, providing potential strategies for AIDS functional cure.

Timeline

Start

2019-04-01

Primary completion

2022-12-31

Completion

2025-12-31

Publications

• Background Liu C, Ma X, Liu B, Chen C, Zhang H. HIV-1 functional cure: will the dream come true? BMC Med. 2015 Nov 20;13:284. doi: 10.1186/s12916-015-0517-y.
• Background Chun TW, Engel D, Berrey MM, Shea T, Corey L, Fauci AS. Early establishment of a pool of latently infected, resting CD4(+) T cells during primary HIV-1 infection. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8869-73. doi: 10.1073/pnas.95.15.8869.
• Background Deng K, Pertea M, Rongvaux A, Wang L, Durand CM, Ghiaur G, Lai J, McHugh HL, Hao H, Zhang H, Margolick JB, Gurer C, Murphy AJ, Valenzuela DM, Yancopoulos GD, Deeks SG, Strowig T, Kumar P, Siliciano JD, Salzberg SL, Flavell RA, Shan L, Siliciano RF. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature. 2015 Jan 15;517(7534):381-5. doi: 10.1038/nature14053. Epub 2015 Jan 7.
• Background McCoy LE, Weiss RA. Neutralizing antibodies to HIV-1 induced by immunization. J Exp Med. 2013 Feb 11;210(2):209-23. doi: 10.1084/jem.20121827.
• Background Eriksson S, Graf EH, Dahl V, Strain MC, Yukl SA, Lysenko ES, Bosch RJ, Lai J, Chioma S, Emad F, Abdel-Mohsen M, Hoh R, Hecht F, Hunt P, Somsouk M, Wong J, Johnston R, Siliciano RF, Richman DD, O'Doherty U, Palmer S, Deeks SG, Siliciano JD. Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies. PLoS Pathog. 2013 Feb;9(2):e1003174. doi: 10.1371/journal.ppat.1003174. Epub 2013 Feb 14.
• Background Hutter G, Nowak D, Mossner M, Ganepola S, Mussig A, Allers K, Schneider T, Hofmann J, Kucherer C, Blau O, Blau IW, Hofmann WK, Thiel E. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med. 2009 Feb 12;360(7):692-8. doi: 10.1056/NEJMoa0802905.
• Background Leong YA, Atnerkar A, Yu D. Human Immunodeficiency Virus Playing Hide-and-Seek: Understanding the TFH Cell Reservoir and Proposing Strategies to Overcome the Follicle Sanctuary. Front Immunol. 2017 May 31;8:622. doi: 10.3389/fimmu.2017.00622. eCollection 2017.
• Background Fellmann C, Gowen BG, Lin PC, Doudna JA, Corn JE. Cornerstones of CRISPR-Cas in drug discovery and therapy. Nat Rev Drug Discov. 2017 Feb;16(2):89-100. doi: 10.1038/nrd.2016.238. Epub 2016 Dec 23.
• Background Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, Kovacs C, Gange SJ, Siliciano RF. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med. 2003 Jun;9(6):727-8. doi: 10.1038/nm880. Epub 2003 May 18.
• Background Finzi D, Hermankova M, Pierson T, Carruth LM, Buck C, Chaisson RE, Quinn TC, Chadwick K, Margolick J, Brookmeyer R, Gallant J, Markowitz M, Ho DD, Richman DD, Siliciano RF. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science. 1997 Nov 14;278(5341):1295-300. doi: 10.1126/science.278.5341.1295.
• Background Chun TW, Stuyver L, Mizell SB, Ehler LA, Mican JA, Baseler M, Lloyd AL, Nowak MA, Fauci AS. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13193-7. doi: 10.1073/pnas.94.24.13193.
• Background Wong JK, Hezareh M, Gunthard HF, Havlir DV, Ignacio CC, Spina CA, Richman DD. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science. 1997 Nov 14;278(5341):1291-5. doi: 10.1126/science.278.5341.1291.
• Background Donahue DA, Wainberg MA. Cellular and molecular mechanisms involved in the establishment of HIV-1 latency. Retrovirology. 2013 Feb 1;10:11. doi: 10.1186/1742-4690-10-11.
• Background Goulder PJ, Watkins DI. HIV and SIV CTL escape: implications for vaccine design. Nat Rev Immunol. 2004 Aug;4(8):630-40. doi: 10.1038/nri1417. No abstract available.
• Background Goonetilleke N, Liu MK, Salazar-Gonzalez JF, Ferrari G, Giorgi E, Ganusov VV, Keele BF, Learn GH, Turnbull EL, Salazar MG, Weinhold KJ, Moore S; CHAVI Clinical Core B; Letvin N, Haynes BF, Cohen MS, Hraber P, Bhattacharya T, Borrow P, Perelson AS, Hahn BH, Shaw GM, Korber BT, McMichael AJ. The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J Exp Med. 2009 Jun 8;206(6):1253-72. doi: 10.1084/jem.20090365. Epub 2009 Jun 1.
• Background Qiao L, Li Y, Xiong G, Liu X, He S, Tong X, Wu S, Hu H, Wang R, Hu H, Chen L, Zhang L, Wu J, Dai F, Lu C, Xiang Z. Effects of altered catecholamine metabolism on pigmentation and physical properties of sclerotized regions in the silkworm melanism mutant. PLoS One. 2012;7(8):e42968. doi: 10.1371/journal.pone.0042968. Epub 2012 Aug 24.
• Background Abaza Y, Kantarjian H, Garcia-Manero G, Estey E, Borthakur G, Jabbour E, Faderl S, O'Brien S, Wierda W, Pierce S, Brandt M, McCue D, Luthra R, Patel K, Kornblau S, Kadia T, Daver N, DiNardo C, Jain N, Verstovsek S, Ferrajoli A, Andreeff M, Konopleva M, Estrov Z, Foudray M, McCue D, Cortes J, Ravandi F. Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab. Blood. 2017 Mar 9;129(10):1275-1283. doi: 10.1182/blood-2016-09-736686. Epub 2016 Dec 21.
• Background Wang P, Qu X, Wang X, Liu L, Zhu X, Zeng H, Zhu H. As2O3 synergistically reactivate latent HIV-1 by induction of NF-kappaB. Antiviral Res. 2013 Dec;100(3):688-97. doi: 10.1016/j.antiviral.2013.10.010.

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