Immunomodulators on HIV-1 Reservoir

Functional Cure Strategy and Clinical Study of AIDS--Study on the Reduction of HIV Viral Reservoir by Immunomodulators (IMs)

The goal of this clinical trial is to learn about the function of immunomodulators in reducing HIV reservoir. The main questions it aims to answer are:

• Are immunomodulators able to reduce HIV reservoirs?
• How do immunomodulators reduce HIV reservoirs? Participants will be randomly and equally divided into three groups, one control group and two trial groups. All three groups will continue to receive antiretroviral therapy. The two experimental groups will additionally be given different immunomodulators lenalidomide and adenosylmethionine, respectively. The effectiveness of immunomodulatory agents in reducing viral reservoirs will be explored by comparing relevant indicators in the three groups.

Study Overview

• Status: Recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Lenalidomide; Drug: Adenosylmethionine

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Biao Zhu; Phone Number: +86-0571-87236437; Email: zhubiao1327@zju.edu.cn
• Study Contact Backup: Name: Xiaorong Peng; Phone Number: +86-0571-87236417; Email: 699xiaorong@163.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The First Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: xiaorong Peng, MD; Phone Number: 15158843398; Email: 699xiaorong@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women age ≥ 18 and ≤ 65 years.
• HIV-1 infection, confirmed by any licensed rapid HIV test and then a licensed Western blot.
• Virologic suppression defined as HIV-1 RNA level below the limit of quantification prior to study entry.
• CD4+ T cell count > 200 cells/mm3 prior to study entry.
• Ability and willingness of participant or legal representative to provide written informed consent and attend study visits as scheduled at a participating site. Willingness of participant to accept the side effects of drugs.
• All participants of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable method of contraception from 4 weeks before the start of the study to 4 weeks after the end of the study.

Exclusion Criteria:

• Breastfeeding or pregnancy, or planned pregnancy during the study.
• Poor treatment adherence.
• Use of immunomodulators or systemic cytotoxic chemotherapy ≤ 6 months prior to study entry.

• Any current diagnosis or past history of a significant cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, neuropsychiatric, psychiatric, or other serious illness. The following laboratory values obtained prior to entry:

  • Absolute neutrophil count (ANC) ≤ 1000/mm3
  • Platelets ≤ 75,000/mm3
• Known allergy/sensitivity or any hypersensitivity to components of study drug or their formulation.
• Unwilling to provide written informed consent.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lenalidomide; Lenalidomide capsules (25 mg) were administered orally on days 1-21 of a 28-day cycle for 24 weeks with continuous antiretroviral therapy. After that, participants will be monitored for another 24 weeks.	Drug: Lenalidomide; Lenalidomide capsules (25 mg) were administered orally on days 1-21 of a 28-day cycle for 24 weeks with continuous antiretroviral therapy.
Experimental: Adenosylmethionine; Adenosylmethionine capsules (1000 mg, twice a day) were administered orally for 24 weeks with continuous antiretroviral therapy. After that, participants will be monitored for another 24 weeks.	Drug: Adenosylmethionine; Adenosylmethionine capsules (1000 mg, twice a day) were administered orally for 24 weeks with continuous antiretroviral therapy.
No Intervention: Control; Participants will continue to receive antiretroviral therapy without other intervention and be monitored for 48 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HIV reservoirs	The size of the HIV reservoir in blood determined by HIV-DNA and CA-HIV-RNA.	48 weeks
Decreased inflammatory factors in HIV-infected patients	The following inflammatory cytokines: interferon-alpha (IFN-α), TNF-α, IL-1, IL-6.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T-cell subsets	Absolute CD4+ and CD8+ T-cell counts and CD4/CD8 ratio were measured on peripheral blood mononuclear cells.	48 weeks
Immune activation	Immune activation measured by the percentage of human leukocyte antigen-DR isotype (HLA-DR) and CD38 expressing T-cells in blood.	48 weeks
Gut microbiome	Diversity and composition of gut microbiome.	48 weeks
Tolerability and safety outcomes	Discontinuation and occurrence of adverse event.	48 weeks

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Investigators: Principal Investigator: Biao Zhu, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2022
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: October 26, 2022
• First Submitted That Met QC Criteria: October 26, 2022
• First Posted (Actual): October 28, 2022

Study Record Updates

• Last Update Posted (Actual): September 14, 2023
• Last Update Submitted That Met QC Criteria: September 12, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: 2022IMs

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
• product manufactured in and exported from the U.S.: No