Therapeutic Vaccine Based on aDC1 Dendritic Cells for the Control of Viremia After ATI in HIV Infected Individuals

Therapeutic Vaccine Based on aDC1 Dendritic Cells for the Control of Viremia After Antiretroviral Therapy Interruption in HIV Infected Individuals

The goal of this interventional study is to validate the strategy of adjuvant therapy with dendritic cells in HIV infection in chronically infected individuals. The main questions it aims to answer are related to the safety and tolerance of the intervention and the virological and immunological impact of immunotherapy with aDC1 in HIV-infected individuals. The study will include 30 diagnosed HIV-infected patients, using antiretroviral therapy, who will be immunized with aDC1 or placebo according to the arms of this study: G1) placebo; G2) aDC1immunization; G3) aDC1 immunization with analytical treatment interruption of ART.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV Vaccine
• Intervention / Treatment: Other: Commercial ringer´s lactate solution; Biological: Alpha-type-1 Polarizing Dendritic Cells (aDC1) unpulsed with HIV peptides; Biological: Alpha-type-1 Polarizing Dendritic Cells (aDC1) pulsed with HIV peptides

Detailed Description

Dendritic cell based immunotherapy is a potential tool to stimulate a specific immune response, as a complementary treatment for HIV-infected individuals using ART. Polarizing DCs are capable to produce high levels of IL-12p70 and induce a strong cytotoxic response that is very useful in viral infections. In this context, we propose to study aDC1 pulsed with relevant HIV peptides for treatment of HIV infected individuals.

The study will include 30 diagnosed HIV-infected patients, using antiretroviral therapy, who will be immunized with aDC1 or placebo according to the arms of this study: G1) placebo; G2) aDC1immunization; G3) aDC1 immunization with analytical treatment interruption of ART. Autologous PBMCs will be collected for baseline parameters and vaccine will be inoculated in 3 doses (with 4 week interval). Three weeks after 3th vaccine inoculation, patients will be followed for 6 months and blood and biopsis samples will be collected for different parameters measurement as immune activation, immunogenicity, humoral response, mucosal cellular immunity and virologic profile and viral reservoir analysis.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Alberto José DS Duarte, PhD; Phone Number: +55 (11) 3061-7499; Email: adjsduar@usp.br

Study Locations

• Brazil
  • São Paulo, Brazil, 05403-000
    • Hospital das Clinicas da Faculdade de Medicina da USP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV infection confirmed according to the criteria of the Department of Chronic Diseases and Sexually Transmitted Infections of the Brazilian Health Ministry;
• Absence of the use of antineoplastic or corticosteroid therapies for a minimum period of six months prior to study entry;
• Absence of comorbidities considered uncontrolled by researchers;
• Viral load ≤ 40 copies/mL, stable (i.e., no > 0.5 log) in the six months prior to the start of the study;
• Blood count of CD4 T lymphocytes ≥ 500 cells/μL, stable (i.e., >25%) in the six months prior to the start of the study;
• Informed consent

Exclusion Criteria:

• Individuals without adequate venous access to the blood collection and apheresis procedure;
• Use of drugs or alcohol in a way that interferes with patients' ability to follow the study requirements;
• Pregnancy, breastfeeding or interest in becoming pregnant during the study period;
• Presence of any other condition that, in the evaluation of researchers is able to promote alteration of the immune system, as well as any disorders that could affect understanding in the process of informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; The participants will receive a placebo, which is the excipient solution of aDC1 cell suspension consisting of a commercial ringer´s lactate solution.	Other: Commercial ringer´s lactate solution; Placebo
Active Comparator: aDC1immunization; The participants will be immunized with aDC1 unpulsed with HIV peptides.	Biological: Alpha-type-1 Polarizing Dendritic Cells (aDC1) unpulsed with HIV peptides; Alpha-type-1 Polarizing Dendritic Cells (aDC1) unpulsed with HIV peptides
Experimental: aDC1 immunization with analytical treatment interruption of ART; The participants will be immunized with aDC1 pulsed with HIV peptides.	Biological: Alpha-type-1 Polarizing Dendritic Cells (aDC1) pulsed with HIV peptides; Alpha-type-1 Polarizing Dendritic Cells (aDC1) pulsed with HIV peptides

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events related to the study product	Number of participants with adverse events related to the study product	Six months
Plasma viral load setpoint after the intervention	Number of participants with changes in the plasma viral load setpoint after the intervention	Six months
Setpoint of CD4+ T lymphocyte count after the intervention	Number of participants with changes in the setpoint of CD4+ T lymphocyte count after the intervention	Six months

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Investigators: Principal Investigator: Alberto José DS Duarte, PhD, University of Sao Paulo

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2023
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: March 14, 2023
• First Submitted That Met QC Criteria: March 14, 2023
• First Posted (Actual): March 28, 2023

Study Record Updates

• Last Update Posted (Actual): March 28, 2023
• Last Update Submitted That Met QC Criteria: March 14, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: HIV; Immunotherapy; Polarizing dendritic cells
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Viremia
• Other Study ID Numbers: INHC031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No