Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure
1 other identifier
interventional
30
1 country
1
Brief Summary
It is becoming clear that a combination of interventions will be desirable to achieve HIV cure. Therefore the investigators propose a pilot proof of concept study, using combination of a number of different interventions for eradicating residual plasma viremia and decreasing HIV reservoirs. The investigators hypothesize that, (i) antiretroviral intensification using Maraviroc, and/or dolutegravir with (ii) Dendritic Cell vaccination using autologous HIV, and (iii) purging intervention using the Class III HDACs, Sirtuin-1, and (iv) decreasing the ratio of long-lived central memory (TCM)/transitional memory (TTM) CD4+ T-cells using Auranofin will provide a synergistic impact leading to a sterilizing cure of HIV infection. Results of this study may provide insightful evidence for planning the next steps using the more efficacious combination of intervention strategies towards HIV sterilizing cure.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable
Started Jul 2015
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2015
CompletedFirst Submitted
Initial submission to the registry
December 18, 2015
CompletedFirst Posted
Study publicly available on registry
November 11, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2020
CompletedJuly 28, 2020
July 1, 2020
3.7 years
December 18, 2015
July 25, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Ultrasensitive RNA Viral load,
from baseline and every 4 weeks up to 48 weeks.
Cell-associated HIV RNA
from baseline and every 4 weeks up to 48 weeks.
Episomal DNA
from baseline and every 4 weeks up to 48 weeks
specific HIV antibodies
from baseline and every 4 weeks up to 48 weeks
CD38 and HLA-DR on CD4 and CD8+ cells
from baseline and every 4 weeks up to 48 weeks
PBMC for env sequence evolution
from baseline and every 4 weeks up to 48 weeks
Study Arms (6)
Antiretroviral Treated (ART) Group
NO INTERVENTIONFive patients will receive no further intervention this group (control group)
ART Intensification Group
EXPERIMENTALFive patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks
ART Intensification + Nicotinamide Group
EXPERIMENTALFive patients will receive antiretroviral intensification with maraviroc and dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks.
ART Intensification + Auranofin Group
EXPERIMENTALFive patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks and the gold salt auranofin for 24 weeks.
ART Intensification + DC vaccine Group
EXPERIMENTALFive patients will receive antiretroviral intensification with dolutegravir and for 48 weeks, and dendritic cell vaccine.
Multi Interventional Group
EXPERIMENTALFive patients will receive antiretroviral intensification with dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks, and gold salt for 24 weeks and dendritic cell vaccine.
Interventions
antiretroviral intensification
antiretroviral intensification
Therapeutic vaccination
purging
latency disruption
Eligibility Criteria
You may qualify if:
- \> 18 years old Documented HIV-1 infection.
- Has voluntarily signed ICF.
- On HAART ≥ 2 years, without changes in the 24 weeks immediately prior to screening.
- HIV viral load \<50 copies/mL, and never \> 50 copies/mL on 2 consecutive occasions in the last 2 years. CD4 count nadir.
- \> 350 cells/ mm3 Current CD4 count \> 500 cells/ mm3.
- R5 HIV-1 at Screening as defined by proviral DNA genotropism.
You may not qualify if:
- A subject will NOT be eligible for study participation if he/she meets ANY of the following criteria:
- Any evidence of an active AIDS-defining condition.
- Any significant acute medical illness in the past 8 weeks.
- Women who are pregnant or breastfeeding.
- Use of any of the following within 90 days prior to entry: systemic cytotoxic chemotherapy; investigational agents; immunomodulators (colony-stimulating factors, growth factors, systemic corticosteroids, HIV vaccines, immune globulin, interleukins, interferons); coumadin, warfarin, or other Coumadin derivative anticoagulants. Use of an agent definitely or possibly associated with effects on QT intervals: amiodarone, arsenic trioxide, astemizole, bepridil, chloroquine, chlorpromazine, cisapride, clarithromycin, disopyramide, dofetilide, domperidone, droperidol, erythromycin, halofantrine, haloperidol, ibutilide, levomethadyl, mesoridazine, methadone, pentamidine, pimozide, probucol, procainamide, quinidine, sotalol, sparfloxacin, terfenadine, thioridazine.
- Receipt of compounds with HDAC inhibitor-like activity, such as valproic acid or nicotinamide within the last 30 days. Potential participants may enroll after a 30-day washout period.
- Known hypersensitivity to the components of gold salt, nicotinamide or its analogs.
- Hepatitis B (HBsAg +) or Hepatitis C (HCV RNA +) infection.
- Known renal insufficiency defined as calculated creatinine clearance (Cockcroft Gault formula) \<60 mL/min.
- Subjects with a laboratory abnormality grade 3 or 4 with the following exceptions: pancreatic amylase, cholesterol, triglyceride, gamma glutamyl transpeptidase, bilirubin.
- Any condition which, in the investigators opinion, could compromise the subject's safety or adherence to the trial protocol.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Federal University of São Paulolead
- Fundação de Amparo à Pesquisa do Estado de São Paulocollaborator
- Conselho Nacional de Desenvolvimento Científico e Tecnológicocollaborator
- ViiV Healthcarecollaborator
Study Sites (1)
CCDI
São Paulo, São Paulo, 04040002, Brazil
Related Publications (2)
de Almeida Baptista MV, da Silva LT, Samer S, Oshiro TM, Shytaj IL, Giron LB, Pena NM, Cruz N, Gosuen GC, Ferreira PRA, Cunha-Neto E, Galinskas J, Dias D, Sucupira MCA, de Almeida-Neto C, Salomao R, da Silva Duarte AJ, Janini LM, Hunter JR, Savarino A, Juliano MA, Diaz RS. Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment: interim analysis from a phase II clinical trial. AIDS Res Ther. 2022 Jan 12;19(1):2. doi: 10.1186/s12981-021-00426-z.
PMID: 35022035DERIVEDDiaz RS, Shytaj IL, Giron LB, Obermaier B, Della Libera E Jr, Galinskas J, Dias D, Hunter J, Janini M, Gosuen G, Ferreira PA, Sucupira MC, Maricato J, Fackler O, Lusic M, Savarino A; SPARC Working Group. Potential impact of the antirheumatic agent auranofin on proviral HIV-1 DNA in individuals under intensified antiretroviral therapy: Results from a randomised clinical trial. Int J Antimicrob Agents. 2019 Nov;54(5):592-600. doi: 10.1016/j.ijantimicag.2019.08.001. Epub 2019 Aug 5.
PMID: 31394172DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Professor of Medicine
Study Record Dates
First Submitted
December 18, 2015
First Posted
November 11, 2016
Study Start
July 1, 2015
Primary Completion
March 1, 2019
Study Completion
March 1, 2020
Last Updated
July 28, 2020
Record last verified: 2020-07