Multi Interventional Approaches to Mitigate HIV Reservoirs for the Sustained HIV Remission Without Use of Antiretrovirals
| Registry | NCT06805656 |
|---|---|
| Status | Recruiting |
| Phase | Phase 2 |
| Study type | Interventional; randomized, parallel, masking: none, treatment |
| Enrollment | 70 (Estimated) |
| Sponsor | Federal University of São Paulo (Other); collaborators: Conselho Nacional de Desenvolvimento Científico e Tecnológico, Weill Medical College of Cornell University, Fundação de Amparo à Pesquisa do Estado de São Paulo |
| Conditions | Hiv, HIV I Infection |
| Interventions | Maraviroc, Dolutegravir, Dendritic Cell Vaccine, Auranofin, Sirtuin Histone deacetylase inhibitor (Drug, biological) |
| Dates | start 2026-07-15, primary completion 2027-03-01 (estimated), completion 2028-06-01 (estimated), first posted 2025-02-03, last updated 2026-08-19 |
| Locations | 1 site in Brazil |
Related Papers Related Patents Related Grants Related Experts
All trials for Hiv All trials for HIV I Infection All trials of Maraviroc All trials of Dolutegravir
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 patients 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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Antiretroviral Treated (ART) Group | No intervention | Ten patients will receive no further intervention (control group) | |
| ART Intensification Group | Experimental | Drug: Maraviroc; Drug: Dolutegravir; Biological: Dendritic Cell Vaccine; Drug: Auranofin; Drug: Sirtuin Histone deacetylase inhibitor | Sixty patients will be included in this stage to undergo antiretroviral intensification with dolutegravir, the Sirtuin Histone deacetylase inhibitor nicotinamide for 48 weeks, gold salt (auranofin) for the last 24 weeks and dendritic cell vaccine, with the adjustment to use also maraviroc during the first 48 weeks. |
Sex: All, ages: 18 Years to 65 Years
Inclusion Criteria: \- > 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. 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. Exclusion 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 (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. 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.
| Facility | City | Country | Status |
|---|---|---|---|
| CCDI | São Paulo, São Paulo | Brazil | Recruiting |