Ignite Creation Date:
2025-12-24 @ 11:30 PM
Ignite Modification Date:
2025-12-25 @ 9:17 PM
Study NCT ID:
NCT06805656
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-08-11
First Post:
2022-03-25
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Multi Interventional Approaches to Mitigate HIV Reservoirs Aiming the Sustained HIV Remission Without Antiretrovirals
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000163', 'term': 'Acquired Immunodeficiency Syndrome'}], 'ancestors': [{'id': 'D015658', 'term': 'HIV Infections'}, {'id': 'D000086982', 'term': 'Blood-Borne Infections'}, {'id': 'D003141', 'term': 'Communicable Diseases'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D015229', 'term': 'Sexually Transmitted Diseases, Viral'}, {'id': 'D012749', 'term': 'Sexually Transmitted Diseases'}, {'id': 'D016180', 'term': 'Lentivirus Infections'}, {'id': 'D012192', 'term': 'Retroviridae Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D012897', 'term': 'Slow Virus Diseases'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D007153', 'term': 'Immunologic Deficiency Syndromes'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077592', 'term': 'Maraviroc'}, {'id': 'C562325', 'term': 'dolutegravir'}, {'id': 'C000706173', 'term': 'lentiviral minigene vaccine of COVID-19 coronavirus'}, {'id': 'D001310', 'term': 'Auranofin'}, {'id': 'D009536', 'term': 'Niacinamide'}], 'ancestors': [{'id': 'D003510', 'term': 'Cyclohexanes'}, {'id': 'D003516', 'term': 'Cycloparaffins'}, {'id': 'D006840', 'term': 'Hydrocarbons, Alicyclic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D014230', 'term': 'Triazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D006051', 'term': 'Aurothioglucose'}, {'id': 'D050607', 'term': 'Organogold Compounds'}, {'id': 'D009942', 'term': 'Organometallic Compounds'}, {'id': 'D009539', 'term': 'Nicotinic Acids'}, {'id': 'D000147', 'term': 'Acids, Heterocyclic'}, {'id': 'D011725', 'term': 'Pyridines'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 70}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-09-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-08', 'completionDateStruct': {'date': '2027-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-08-05', 'studyFirstSubmitDate': '2022-03-25', 'studyFirstSubmitQcDate': '2025-01-28', 'lastUpdatePostDateStruct': {'date': '2025-08-11', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-02-03', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-07-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Evolution of viral load of HIV RNA over the time frame of study', 'timeFrame': 'baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to 36 months after antiretroviral ATI', 'description': 'Viral load count by qPCR at each time point to measure the viral persistence in each participant'}, {'measure': 'Evolution of total DNA and episomal HIV in PBMCs', 'timeFrame': 'baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to 36 months after antiretroviral ATI', 'description': 'Quantification of total DNA and episomal HIV in a virological assay'}, {'measure': 'Evolution of cell-associated HIV RNA in PBMCs over the study time frame', 'timeFrame': 'baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to 36 months after antiretroviral ATI', 'description': 'Quantification of HIV RNA in PBMCs by qPCR'}, {'measure': 'Evolution of total DNA and episomal HIV DNA in lymphoid tissue (rectal biopsy)', 'timeFrame': 'baseline, week 48, after resurgence of viremia in the analytical interruption of antiretrovirals, or after 24 and 96 weeks after analytical interruption of antiretrovirals.', 'description': 'Quantification by in-house virological assay'}, {'measure': 'Evolution of the HIV DNA sequence of the V3 region of gp 120, protease, reverse transcriptase and integrase regions of the pol gene, and of the gag gene', 'timeFrame': 'baseline, week 24, week 48, after resurgence of viremia after ATI and before reintroduction of ART', 'description': 'NGS sequencing of the V3 region of gp120, the protease, reverse transcriptase, and integrase regions of the pol gene, and of the gag gene of HIV DNA'}, {'measure': 'Evolution of the HIV RNA sequence of the V3 region of gp 120, protease, reverse transcriptase and integrase regions of the pol gene, and of the gag gene', 'timeFrame': 'baseline, week 24, week 48, after resurgence of viremia after ATI and before reintroduction of ART', 'description': 'NGS sequencing of the V3 region of gp120, the protease, reverse transcriptase, and integrase regions of the pol gene, and of the gag gene of HIV RNA'}, {'measure': 'Evolution of CD4 + and CD8 + T lymphocyte count', 'timeFrame': 'baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to a total of 36 months after ATI.', 'description': 'Count by flow cytometry of CD4+ and CD8+ lymphocytes'}, {'measure': 'Evolution of percentages of CD38 and HLA DR in CD4 + and CD8 + T lymphocytes', 'timeFrame': 'baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to 36 months after antiretroviral ATI', 'description': 'Measurement by flow cytometry of cell activation of CD4+ and CD8+ T lymphocytes as a means of assessing immune and inflammatory responses'}, {'measure': 'Evolution of plasma cytokines IL-2, IL-4, IL-6, IL-10, IL-17, TNF and IFN-γ', 'timeFrame': 'baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to 36 months after antiretroviral ATI', 'description': 'Measurement by ELISA Assay of plasma cytokines IL-2, IL-4, IL-6, IL-10, IL-17, TNF and IFN-γ as a means of assessing immune and inflammatory responses'}, {'measure': 'Changes in bacterial translocation levels by quantification of plasma LPS levels', 'timeFrame': 'baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to 36 months after antiretroviral ATI', 'description': 'Assay for determining the proinflammatory level of endotoxin (LPS)'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Dendritic Cell vaccination', 'antiretroviral intensification', 'Auranofin', 'Histone Deacetylase Inhibitor', 'residual viral replication', 'HIV sanctuaries', 'HIV latency'], 'conditions': ['Hiv', 'HIV I Infection']}, 'descriptionModule': {'briefSummary': "A modern and urgent challenge in fighting HIV infection is to achieve sustained HIV remission without the use of antiretrovirals. The investigators' preliminary data indicate that the use of combined strategies to mitigate the HIV proviral reservoir size among individuals with suppressive antiretroviral treatment achieved unprecedented results in the reduction of HIV DNA present in these cells and in the reduction of CD4 + and CD8 + T cell activation. Combined interventions include intensified antiretroviral treatment to mitigate residual HIV replication, use of a histone deacetylase inhibitor to interrupt viral latency, use of an anti-proliferative medication to reduce long-lived T cells that harbor HIV and a personalized dendritic cell therapy vaccine to eliminate cells with latent HIV infection or cells present in viral sanctuaries. Due to the good results obtained in the exploratory stage of the project, the investigators propose to expand it by recruiting a larger number of patient to confirm the previously obtained results and to generate new insights related to the mechanisms involved in viral latency, latency disruption and the effects of analytical treatment interruption of antiretrovirals among patients undergoing all above mentioned interventions."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'genderBased': True, 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n\\- \\> 18 years old \\< 65 years old Documented HIV-1 infection. Has voluntarily signed ICF. On HAART ≥ 2 years, without changes in the 24 weeks immediately prior to screening.\n\nHIV viral load \\<50 copies/mL, and never \\> 50 copies/mL on 2 consecutive occasions in the last 2 years. CD4 count nadir.\n\n\\> 350 cells/ mm3 Current CD4 count \\> 500 cells/ mm3. R5 HIV-1 at Screening as defined by proviral DNA genotropism.\n\nExclusion Criteria:\n\n\\- 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 (colonystimulating 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.\n\nReceipt 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.\n\nKnown hypersensitivity to the components of gold salt, nicotinamide or its analogs.\n\nHepatitis B (HBsAg +) or Hepatitis C (HCV RNA +) infection. Known renal insufficiency defined as calculated creatinine clearance (Cockcroft Gault formula) \\<60 mL/min.\n\nSubjects with a laboratory abnormality grade 3 or 4 with the following exceptions: pancreatic amylase, cholesterol, triglyceride, gamma glutamyl transpeptidase, bilirubin.\n\nAny condition which, in the investigators opinion, could compromise the subject's safety or adherence to the trial protocol."}, 'identificationModule': {'nctId': 'NCT06805656', 'briefTitle': 'Multi Interventional Approaches to Mitigate HIV Reservoirs Aiming the Sustained HIV Remission Without Antiretrovirals', 'organization': {'class': 'OTHER', 'fullName': 'Federal University of São Paulo'}, 'officialTitle': 'Multi Interventional Approaches to Mitigate HIV Reservoirs Aiming the Sustained HIV Remission Without Use of Antiretrovirals', 'orgStudyIdInfo': {'id': 'SPARC-11'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'NO_INTERVENTION', 'label': 'Antiretroviral Treated (ART) Group', 'description': 'Ten patients will receive no further intervention (control group)'}, {'type': 'EXPERIMENTAL', 'label': 'ART Intensification Group', 'description': 'Sixty patients will be included in this stage to undergo the same interventions as Group 6 of the study under registration NCT02961829 of clinicaltrials.gov (antiretroviral intensification with dolutegravir and the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks, and gold salt for 24 weeks and dendritic cell vaccine.), with the adjustment to use also the maraviroc during the first 44 weeks.', 'interventionNames': ['Drug: Maraviroc', 'Drug: Dolutegravir', 'Biological: Dendritic Cell Vaccine', 'Drug: Auranofin', 'Drug: Sirtuin Histone deacetylase inhibitor']}], 'interventions': [{'name': 'Maraviroc', 'type': 'DRUG', 'otherNames': ['Selzentry', 'Celsentri'], 'description': 'antiretroviral intensification', 'armGroupLabels': ['ART Intensification Group']}, {'name': 'Dolutegravir', 'type': 'DRUG', 'otherNames': ['Tivicay'], 'description': 'antiretroviral intensification', 'armGroupLabels': ['ART Intensification Group']}, {'name': 'Dendritic Cell Vaccine', 'type': 'BIOLOGICAL', 'otherNames': ['DC Vaccine'], 'description': 'therapeutic vaccination', 'armGroupLabels': ['ART Intensification Group']}, {'name': 'Auranofin', 'type': 'DRUG', 'otherNames': ['Gold Salt'], 'description': 'purging', 'armGroupLabels': ['ART Intensification Group']}, {'name': 'Sirtuin Histone deacetylase inhibitor', 'type': 'DRUG', 'otherNames': ['Nicotinamide'], 'description': 'latency disruption', 'armGroupLabels': ['ART Intensification Group']}]}, 'contactsLocationsModule': {'locations': [{'city': 'São Paulo', 'state': 'São Paulo', 'country': 'Brazil', 'contacts': [{'name': 'Ricardo S Diaz, M.D.; /PhD', 'role': 'CONTACT'}], 'facility': 'CCDI', 'geoPoint': {'lat': -23.5475, 'lon': -46.63611}}], 'centralContacts': [{'name': 'Ricardo S Diaz, M.D.; PhD', 'role': 'CONTACT', 'email': 'rsdiaz@catg.com.br', 'phone': '+55 11 991090445'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'Because of the range of personal data gathered, IPD will be shared on request when properly anonymized.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Federal University of São Paulo', 'class': 'OTHER'}, 'collaborators': [{'name': 'Conselho Nacional de Desenvolvimento Científico e Tecnológico', 'class': 'OTHER_GOV'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Associated Professor', 'investigatorFullName': 'Ricardo Sobhie Diaz', 'investigatorAffiliation': 'Federal University of São Paulo'}}}}