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

NCT06805656 | Not Yet Recruiting Phase 2

• 1 other identifier: SPARC-11
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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

Keywords

Dendritic Cell vaccination; antiretroviral intensification; Auranofin; Histone Deacetylase Inhibitor; residual viral replication; HIV sanctuaries; HIV latency

Outcome Measures

Primary Outcomes (10)

• Evolution of viral load of HIV RNA over the time frame of study

  Viral load count by qPCR at each time point to measure the viral persistence in each participant

  baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to 36 months after antiretroviral ATI

• Evolution of total DNA and episomal HIV in PBMCs

  Quantification of total DNA and episomal HIV in a virological assay

  baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to 36 months after antiretroviral ATI

• Evolution of cell-associated HIV RNA in PBMCs over the study time frame

  Quantification of HIV RNA in PBMCs by qPCR

  baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to 36 months after antiretroviral ATI

• Evolution of total DNA and episomal HIV DNA in lymphoid tissue (rectal biopsy)

  Quantification by in-house virological assay

  baseline, week 48, after resurgence of viremia in the analytical interruption of antiretrovirals, or after 24 and 96 weeks after analytical interruption of antiretrovirals.

• 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

  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

  baseline, week 24, week 48, after resurgence of viremia after ATI and before reintroduction of ART

• 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

  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

  baseline, week 24, week 48, after resurgence of viremia after ATI and before reintroduction of ART

• Evolution of CD4 + and CD8 + T lymphocyte count

  Count by flow cytometry of CD4+ and CD8+ lymphocytes

  baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to a total of 36 months after ATI.

• Evolution of percentages of CD38 and HLA DR in CD4 + and CD8 + T lymphocytes

  Measurement by flow cytometry of cell activation of CD4+ and CD8+ T lymphocytes as a means of assessing immune and inflammatory responses

  baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to 36 months after antiretroviral ATI

• Evolution of plasma cytokines IL-2, IL-4, IL-6, IL-10, IL-17, TNF and IFN-γ

  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

  baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to 36 months after antiretroviral ATI

• Changes in bacterial translocation levels by quantification of plasma LPS levels

  Assay for determining the proinflammatory level of endotoxin (LPS)

  baseline, weeks 12, 24, 36 and 48 and every 3 weeks after the antiretroviral ATI up to 36 months after antiretroviral ATI

Study Arms (2)

Antiretroviral Treated (ART) Group

NO INTERVENTION

Ten patients will receive no further intervention (control group)

ART Intensification Group

EXPERIMENTAL

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.

Drug: Maraviroc; Drug: Dolutegravir; Biological: Dendritic Cell Vaccine; Drug: Auranofin; Drug: Sirtuin Histone deacetylase inhibitor

Interventions

Maraviroc DRUG

antiretroviral intensification

Also known as: Selzentry, Celsentri

ART Intensification Group

Dolutegravir DRUG

antiretroviral intensification

Also known as: Tivicay

ART Intensification Group

Dendritic Cell Vaccine BIOLOGICAL

therapeutic vaccination

Also known as: DC Vaccine

ART Intensification Group

Auranofin DRUG

purging

Also known as: Gold Salt

ART Intensification Group

Sirtuin Histone deacetylase inhibitor DRUG

latency disruption

Also known as: Nicotinamide

ART Intensification Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- \> 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.

You may not qualify if:

• \- 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.

Sponsors & Collaborators

• Federal University of São Paulo: lead
• Conselho Nacional de Desenvolvimento Científico e Tecnológico: collaborator

Study Sites (1)

CCDI

São Paulo, São Paulo, Brazil

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Maraviroc; dolutegravir; lentiviral minigene vaccine of COVID-19 coronavirus; Auranofin; Niacinamide

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aurothioglucose; Organogold Compounds; Organometallic Compounds; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Central Study Contacts

Ricardo S Diaz, M.D.; PhD

CONTACT

+55 11 991090445; rsdiaz@catg.com.br

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associated Professor

Study Record Dates

• First Submitted: March 25, 2022
• First Posted: February 3, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)