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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hiv; HIV I Infection
• Intervention / Treatment: Drug: Maraviroc; Drug: Dolutegravir; Drug: Sirtuin Histone deacetylase inhibitor; Drug: Auranofin; Biological: Dendritic Cell Vaccine

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ricardo S Diaz, M.D.; PhD; Phone Number: +55 11 991090445; Email: rsdiaz@catg.com.br

Study Locations

• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil
      • CCDI
      • Contact: Ricardo S Diaz, M.D.; /PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Antiretroviral Treated (ART) Group; Ten patients will receive no further intervention (control group)
Experimental: 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.	Drug: Maraviroc; antiretroviral intensification; Other Names: Celsentri; Selzentry; Drug: Dolutegravir; antiretroviral intensification; Other Names: Tivicay; Drug: Sirtuin Histone deacetylase inhibitor; latency disruption; Other Names: Nicotinamide; Drug: Auranofin; purging; Other Names: Gold Salt; Biological: Dendritic Cell Vaccine; therapeutic vaccination; Other Names: DC Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Federal University of São Paulo
• Collaborators: Conselho Nacional de Desenvolvimento Científico e Tecnológico

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 25, 2022
• First Submitted That Met QC Criteria: January 28, 2025
• First Posted (Actual): February 3, 2025

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Histone Deacetylase Inhibitor; Auranofin; HIV latency; antiretroviral intensification; residual viral replication; HIV sanctuaries; Dendritic Cell vaccination
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Triazoles; Acids, Heterocyclic; Nicotinic Acids; Organometallic Compounds; Aurothioglucose; Organogold Compounds; Maraviroc; Niacinamide; Auranofin; dolutegravir; lentiviral minigene vaccine of COVID-19 coronavirus
• Other Study ID Numbers: SPARC-11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Because of the range of personal data gathered, IPD will be shared on request when properly anonymized.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No