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

NCT03980665 | Unknown Phase 1

• 1 other identifier: 20170812V1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV/AIDS

Keywords

Arsenic Trioxide; cART; HIV-1 reservoir; functional cure

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-emergent adverse events of arsenic trioxide combined with cART

  To observe the adverse events of arsenic trioxide combined with cART when treating with HIV-infected patients during the clinical trial

  6 Months

Secondary Outcomes (1)

• HIV-1 reservoir

  6 Months

Other Outcomes (1)

• HIV-specific immunity

  6 Months

Study Arms (2)

Arsenic trioxide combined with cART

EXPERIMENTAL

Receiving intravenous arsenic trioxide, 0.16mg/kg/day, no more than 10 mg per-day , two to four weeks, combined with continuous cART after attaining plasma HIV-1 suppression (plasma HIV RNA \<50 cp/ml) and CD4+ cell count more than 350 cells/ul over 1 year by cART, without active HCV or HBV infection or opportunistic infections.

Drug: Arsenic Trioxide

Without arsenic trioxide therapy

NO INTERVENTION

Only receiving cART without arsenic Trioxide after attaining plasma HIV-1 suppression (plasma HIV RNA \<50 cp/ml) and CD4+ cell count more than 350 cells/ul over 1 year by cART, without active HCV or HBV infection or opportunistic infections.

Interventions

Arsenic Trioxide DRUG

a arsenic class of mineral, clinically approved for treating acute promyelocytic leukemia

Also known as: Arsenic Trioxide Injectable Solution

Arsenic trioxide combined with cART

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• HIV infection confirmed
• Receiving HAART more than 12 months.
• HIV viral-load \< 50 copies/ml and CD4+ cell count more than 350 cells/ul.
• Without serious heart, lung, liver or kidney disease.
• Participants know about the study and sign informed consent.

You may not qualify if:

• With serious active HBV or HCV infection or opportunistic infections
• With serious chronic disease such as diabetes, mental illness,et al
• History of suffering from pancreatitis during HAART.
• Pregnant or breast-fed.
• With poor adherence.
• Unable to complete the follow up.

Sponsors & Collaborators

• Guangzhou 8th People's Hospital: lead
• Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences: collaborator

Study Sites (1)

Guangzhou 8th People's Hospital

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (18)

• 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.

  PMID: 26588898 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.

  PMID: 9671771 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.

  PMID: 25561180 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.

  PMID: 23401570 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.

  PMID: 23459007 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.

  PMID: 19213682 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.

  PMID: 28620380 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.

  PMID: 28008168 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.

  PMID: 12754504 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.

  PMID: 9360927 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.

  PMID: 9371822 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.

  PMID: 9360926 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.

  PMID: 23375003 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.

  PMID: 15286729 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.

  PMID: 19487423 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.

  PMID: 22937004 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.

  PMID: 28003274 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.

  PMID: 24416773 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Arsenic Trioxide

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds

Study Officials

• Weiping Cai, Bachelor

  Guangzhou 8th People's Hospital

  STUDY CHAIR

Central Study Contacts

Linghua Li, Doctor

CONTACT

020-83710825; llheliza@126.com

Weiping Cai, Bachelor

CONTACT

020-83710816; gz8hcwp@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Chief physician

Model Details: The control arm includes HIV-infected patients with the therapy of Antiretroviral drugs.

Study Record Dates

• First Submitted: June 7, 2019
• First Posted: June 10, 2019
• Study Start: April 1, 2019
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2025
• Last Updated: September 14, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)