Chronic InfectionNCT02961829
Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure
A study testing Maraviroc, Dolutegravir and Dendritic Cell Vaccine in people with Chronic Infection and HIV, run by Federal University of São Paulo at 1 site in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years, men only
- Conditions the study is for
- Chronic Infection, HIV
- What is being tested?
- Maraviroc, Dolutegravir and Dendritic Cell Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteBrazil
- Study dates
- Jul 2015to Mar 2020
- Phase
- Interventional
- 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
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- > 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Conditions
- Chronic Infection, HIV
- Being tested
- Maraviroc, Dolutegravir, Dendritic Cell Vaccine, Auranofin, Sirtuin Histone deacetylase inhibitor
- Keywords
- Dendritic Cell vaccination using, antiretroviral intensification, Auranofin, Histone Deacetylase Inhibitor, residual viral replication, HIV sanctuaries, HIV latency
- Medical subject headings
- Persistent Infection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MaravirocDrug
Also called Selzentry, Celsentri
antiretroviral intensification
DolutegravirDrug
Also called Tivicay
antiretroviral intensification
Dendritic Cell VaccineBiological
Also called DC Vaccine
Therapeutic vaccination
AuranofinDrug
Also called Gold Salt
purging
Sirtuin Histone deacetylase inhibitorDrug
Also called Nicotinamide
latency disruption
| Study group | Role | What they receive |
|---|---|---|
| Antiretroviral Treated (ART) Group | No intervention | Five patients will receive no further intervention this group (control group) |
| ART Intensification Group | Experimental | Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks Receives: Drug: Maraviroc; Drug: Dolutegravir |
| ART Intensification + Nicotinamide Group | Experimental | Five patients will receive antiretroviral intensification with maraviroc and dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks. Receives: Drug: Maraviroc; Drug: Dolutegravir; Drug: Sirtuin Histone deacetylase inhibitor |
| ART Intensification + Auranofin Group | Experimental | Five patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks and the gold salt auranofin for 24 weeks. Receives: Drug: Maraviroc; Drug: Dolutegravir; Drug: Auranofin |
| ART Intensification + DC vaccine Group | Experimental | Five patients will receive antiretroviral intensification with dolutegravir and for 48 weeks, and dendritic cell vaccine. Receives: Drug: Dolutegravir; Biological: Dendritic Cell Vaccine |
| Multi Interventional Group | Experimental | Five 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. Receives: Drug: Dolutegravir; Biological: Dendritic Cell Vaccine; Drug: Auranofin; Drug: Sirtuin Histone deacetylase inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ultrasensitive RNA Viral load,
Measured: from baseline and every 4 weeks up to 48 weeks.
Cell-associated HIV RNA
Measured: from baseline and every 4 weeks up to 48 weeks.
Episomal DNA
Measured: from baseline and every 4 weeks up to 48 weeks
specific HIV antibodies
Measured: from baseline and every 4 weeks up to 48 weeks
CD38 and HLA-DR on CD4 and CD8+ cells
Measured: from baseline and every 4 weeks up to 48 weeks
PBMC for env sequence evolution
Measured: from baseline and every 4 weeks up to 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2016 (estimated)
- Study startJul 2015
- Primary completionMar 2019
- Study completionMar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic InfectionStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federal University of São Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, ViiV Healthcare
- Responsible party
- Principal investigator, Ricardo Sobhie Diaz, MD, PHD, Federal University of São Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02961829
- Sponsor's protocol ID
- SPARC-7
- Status last verified
- Jul 2020
- First submitted
- 18 Dec 2015
- Last updated
- 28 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 35022035Diaz 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.
PubMed 31394172
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure
- ClinicalTrials.gov ID
- NCT02961829
- Acronym / sponsor ID
- SPARC-7
- Conditions
- Chronic Infection, HIV
- Keywords
- Dendritic Cell vaccination using, antiretroviral intensification, Auranofin, Histone Deacetylase Inhibitor, residual viral replication, HIV sanctuaries, HIV latency
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Federal University of São PauloUniversity, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, ViiV Healthcare
- Study start
- Jul 2015 (actual)
- Primary completion
- Mar 2019 (actual)
- Study completion
- Mar 2020 (actual)
- First posted
- 11 Nov 2016 (estimated)
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Antiretroviral Treated (ART) Group | No intervention | –Five patients will receive no further intervention this group (control group) |
| ART Intensification Group | Experimental | Drug: Maraviroc, Drug: DolutegravirFive patients will receive antiretroviral intensification with maraviroc and dolutegravir for 48 weeks |
| ART Intensification + Nicotinamide Group | Experimental | Drug: Maraviroc, Drug: Dolutegravir, Drug: Sirtuin Histone deacetylase inhibitorFive patients will receive antiretroviral intensification with maraviroc and dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks. |
| ART Intensification + Auranofin Group | Experimental | Drug: Maraviroc, Drug: Dolutegravir, Drug: AuranofinFive 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 | Experimental | Drug: Dolutegravir, Biological: Dendritic Cell VaccineFive patients will receive antiretroviral intensification with dolutegravir and for 48 weeks, and dendritic cell vaccine. |
| Multi Interventional Group | Experimental | Drug: Dolutegravir, Biological: Dendritic Cell Vaccine, Drug: Auranofin, Drug: Sirtuin Histone deacetylase inhibitorFive 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- > 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.
Key exclusion criteria (11 listed)
- 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.
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 |
|---|---|---|
| MaravirocAlso: Selzentry, Celsentriantiretroviral intensification | Drug | ART Intensification + Auranofin Group, ART Intensification + Nicotinamide Group, ART Intensification Group |
| DolutegravirAlso: Tivicayantiretroviral intensification | Drug | ART Intensification + Auranofin Group, ART Intensification + DC vaccine Group, ART Intensification + Nicotinamide Group, ART Intensification Group, Multi Interventional Group |
| Dendritic Cell VaccineAlso: DC VaccineTherapeutic vaccination | Biological | ART Intensification + DC vaccine Group, Multi Interventional Group |
| AuranofinAlso: Gold Saltpurging | Drug | ART Intensification + Auranofin Group, Multi Interventional Group |
| Sirtuin Histone deacetylase inhibitorAlso: Nicotinamidelatency disruption | Drug | ART Intensification + Nicotinamide Group, Multi Interventional Group |
Primary outcome
Ultrasensitive RNA Viral load,
Time frame: from baseline and every 4 weeks up to 48 weeks.
Cell-associated HIV RNA
Time frame: from baseline and every 4 weeks up to 48 weeks.
Episomal DNA
Time frame: from baseline and every 4 weeks up to 48 weeks
specific HIV antibodies
Time frame: from baseline and every 4 weeks up to 48 weeks
CD38 and HLA-DR on CD4 and CD8+ cells
Time frame: from baseline and every 4 weeks up to 48 weeks
PBMC for env sequence evolution
Time frame: from baseline and every 4 weeks up to 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2020.
- Derived from this study: PubMed 35022035de 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.
- Derived from this study: PubMed 31394172Diaz 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.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Maraviroc, Dolutegravir and Dendritic Cell Vaccine in people with Chronic Infection and HIV, run by Federal University of São Paulo at 1 site in Brazil.
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 6 inclusion and 11 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: finished, as of the sponsor's last update on 28 Jul 2020. 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 Brazil. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ultrasensitive RNA Viral load, (time frame: from baseline and every 4 weeks up to 48 weeks.). The study lists 6 primary outcomes in all. 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 NCT02961829, which also lists 2 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 28 Jul 2020.