Multi Interventional Approaches to Mitigate HIV Reservoirs Aiming the Sustained HIV Remission Without Antiretrovirals

NCT ID: NCT06805656

Last Updated: 2025-08-11

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-01
• Study Completion Date: 2027-12-31

Brief Summary

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.

Conditions

Hiv; HIV I Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Antiretroviral Treated (ART) Group

Ten patients will receive no further intervention (control group)

Group Type: NO_INTERVENTION

No interventions assigned to this group

ART Intensification Group

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.

Group Type: EXPERIMENTAL

Maraviroc

Intervention Type: DRUG

antiretroviral intensification

Dolutegravir

Intervention Type: DRUG

antiretroviral intensification

Dendritic Cell Vaccine

Intervention Type: BIOLOGICAL

therapeutic vaccination

Auranofin

Intervention Type: DRUG

purging

Sirtuin Histone deacetylase inhibitor

Intervention Type: DRUG

latency disruption

Interventions

Maraviroc

antiretroviral intensification

Intervention Type: DRUG

Dolutegravir

antiretroviral intensification

Intervention Type: DRUG

Dendritic Cell Vaccine

therapeutic vaccination

Intervention Type: BIOLOGICAL

Auranofin

purging

Intervention Type: DRUG

Sirtuin Histone deacetylase inhibitor

latency disruption

Intervention Type: DRUG

Other Intervention Names

Selzentry; Celsentri; Tivicay; DC Vaccine; Gold Salt; Nicotinamide

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Conselho Nacional de Desenvolvimento Científico e Tecnológico

OTHER_GOV

Sponsor Role: collaborator

Federal University of São Paulo

OTHER

Sponsor Role: lead

Responsible Party

Ricardo Sobhie Diaz

Associated Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

CCDI

São Paulo, São Paulo, Brazil

Countries

Brazil

Central Contacts

Ricardo S Diaz, M.D.; PhD

Role: CONTACT

rsdiaz@catg.com.br

+55 11 991090445

Facility Contacts

Ricardo S Diaz, M.D.; /PhD

Role: primary

Other Identifiers

SPARC-11

Identifier Type: -

Identifier Source: org_study_id