HIV/AIDSPhase 1NCT03980665
The Effect of Arsenic Trioxide on Eliminating HIV-1 Reservoir Combined With cART
A Phase 1 study testing Arsenic Trioxide in people with HIV/AIDS, run by Guangzhou 8th People's Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- HIV/AIDS
- What is being tested?
- Arsenic Trioxide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2019to 31 Dec 2025
- Phase
- Phase 1
- 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 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Guangzhou 8th People's Hospital
Guangzhou, Guangdong, 510060
Linghua LI, PhD, 020-83710825, llheliza@126.com
C
About this study
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.
Read the detailed description
Although combined antiretroviral therapy (cART) could control human immunodeficiency virus type 1 (HIV-1) infection, the persistence of HIV-1 viral reservoir make it extremely difficult to achieving cure of AIDS. The shock and kill strategy has been extensively practiced. The latency reversing agents (LRAs) could reactivate latent HIV-1 and then the reactivated virus could be eradicated. However, no appropriate activator has been found nor manufactured. Our previous work found that the arsenic trioxide, clinically approved for treating acute promyelocytic leukemia,could efficiently reactivate latent provirus in CD4+T cells from HIV-1 patients and Simian immunodeficiency virus (SIV)-infected macaques, without significant systemic T cell activation and inflammatory responses. In this study, we are going to study the safety of and efficacy of arsenic trioxide combined with cART in 20 HIV-1 infected patients, by observing adverse events,HIV-1 reservoir, HIV-1 load, and some immune index.
- Conditions
- HIV/AIDS
- Being tested
- Arsenic Trioxide
- Keywords
- Arsenic Trioxide, cART, HIV-1 reservoir, functional cure
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arsenic TrioxideDrug
Also called Arsenic Trioxide Injectable Solution
a arsenic class of mineral, clinically approved for treating acute promyelocytic leukemia
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 Months
Secondary outcomes (1)
HIV-1 reservoir
To assay the HIV-1 viral load in the peripheral blood Mono-nuclear cells and plasma
Measured: 6 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2019
- Study start1 Apr 2019
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for HIV/AIDSStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The control arm includes HIV-infected patients with the therapy of Antiretroviral drugs.
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangzhou 8th People's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences
- Responsible party
- Principal investigator, Linghua LI, Guangzhou 8th People's Hospital
- Investigators
- Weiping Cai, Bachelor, Study chair, Guangzhou 8th People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03980665
- Sponsor's protocol ID
- 20170812V1
- Status last verified
- Sep 2022
- First submitted
- 7 Jun 2019
- Last updated
- 14 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26588898Chun 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.
PubMed 9671771Deng 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.
PubMed 25561180McCoy 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.
PubMed 23401570Eriksson 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.
PubMed 23459007Hutter 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.
PubMed 19213682Leong 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.
PubMed 28620380Fellmann 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.
PubMed 28008168Siliciano 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.
PubMed 12754504Finzi 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.
PubMed 9360927Chun 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.
PubMed 9371822Wong 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.
PubMed 9360926Donahue 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.
PubMed 23375003Goulder 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.
PubMed 15286729Goonetilleke 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.
PubMed 19487423
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Arsenic Trioxide on Eliminating HIV-1 Reservoir Combined With cART
- ClinicalTrials.gov ID
- NCT03980665
- Acronym / sponsor ID
- 20170812V1
- Conditions
- HIV/AIDS
- Keywords
- Arsenic Trioxide, cART, HIV-1 reservoir, functional cure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Guangzhou 8th People's HospitalUniversity, hospital or other
- Collaborators
- Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 10 Jun 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.
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.
Detailed description
Although combined antiretroviral therapy (cART) could control human immunodeficiency virus type 1 (HIV-1) infection, the persistence of HIV-1 viral reservoir make it extremely difficult to achieving cure of AIDS. The shock and kill strategy has been extensively practiced. The latency reversing agents (LRAs) could reactivate latent HIV-1 and then the reactivated virus could be eradicated. However, no appropriate activator has been found nor manufactured. Our previous work found that the arsenic trioxide, clinically approved for treating acute promyelocytic leukemia,could efficiently reactivate latent provirus in CD4+T cells from HIV-1 patients and Simian immunodeficiency virus (SIV)-infected macaques, without significant systemic T cell activation and inflammatory responses. In this study, we are going to study the safety of and efficacy of arsenic trioxide combined with cART in 20 HIV-1 infected patients, by observing adverse events,HIV-1 reservoir, HIV-1 load, and some immune index.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The control arm includes HIV-infected patients with the therapy of Antiretroviral drugs.
| Arm | Type | Receives |
|---|---|---|
| Arsenic trioxide combined with cART | Experimental | Drug: Arsenic TrioxideReceiving 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. |
| 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arsenic TrioxideAlso: Arsenic Trioxide Injectable Solutiona arsenic class of mineral, clinically approved for treating acute promyelocytic leukemia | Drug | Arsenic trioxide combined with cART |
Primary outcome
Incidence of treatment-emergent adverse events of arsenic trioxide combined with cART
Time frame: 6 Months
To observe the adverse events of arsenic trioxide combined with cART when treating with HIV-infected patients during the clinical trial
1 secondary outcome
HIV-1 reservoir
Time frame: 6 Months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2022.
- Background: PubMed 26588898Liu 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: PubMed 9671771Chun 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: PubMed 25561180Deng 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: PubMed 23401570McCoy 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: PubMed 23459007Eriksson 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: PubMed 19213682Hutter 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: PubMed 28620380Leong 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: PubMed 28008168Fellmann 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: PubMed 12754504Siliciano 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: PubMed 9360927Finzi 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: PubMed 9371822Chun 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: PubMed 9360926Wong 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.
- 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.
Weiping Cai, Bachelor study chair
Guangzhou 8th People's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Arsenic Trioxide in people with HIV/AIDS, run by Guangzhou 8th People's Hospital at 1 site in China.
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 5 inclusion and 6 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 14 Sep 2022. 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 China. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Linghua Li, Doctor (020-83710825, llheliza@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment-emergent adverse events of arsenic trioxide combined with cART (time frame: 6 Months). 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 NCT03980665, which also lists 18 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 14 Sep 2022.