The Role of the Gastrointestinal-associated Lymphoid Tissue in the Cure of HIV Infection

The objective of this study is to understand the effects of HIV cure strategies on the virus and immune cells that reside within the gastrointestinal tract. Subjects receiving therapies with the potential for HIV cure will undergo a colonoscopy to obtain gastrointestinal tissue for research assays. This study will test whether receiving these therapies will induce changes in the immune cells in the gastrointestinal tract and reduce the tissue-associated HIV viral levels.

Study Overview

• Status: Recruiting
• Conditions: HIV Infection
• Intervention / Treatment: Procedure: Colonoscopy

Detailed Description

After almost forty years from its first discovery, Human Immunodeficiency Virus (HIV) infection remains uncurable. The major obstacle to a cure for HIV infection is the integration of HIV into the host genome and its persistence in populations of long-lived immune cells subsets. These long-lived resting cells represent a reservoir of transcriptionally silent HIV and they are mostly localized in the secondary lymphoid tissue and the gastrointestinal associated lymphoid tissue (GALT).

The most promising HIV cure strategies relay on molecules which can induce enhanced immune responses through antibody mediated effects such as antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) as well as enhanced CD8+ T cells activity.

The specific purpose of this study is to evaluate whether the proposed treatment strategies for HIV cure, can induce changes in the gastrointestinal associated immune system (GALT) effector immune cells such as NK cells, cytotoxic CD8+ T Cells and whether treatment with these molecules leads to changes in the amount of tissue-associated HIV virus within the GALT. The results from the proposed study will inform on the ability of these molecules to exert their effect on this critical site of HIV latency and persistence and thus advance the field on their HIV cure potential.

Subjects receiving treatment with the potential for HIV cure will undergo a colonoscopy to obtain gastrointestinal tissue for research assays. The research proposal will test the hypothesis of whether these molecules are able to induce changes in the immune cells in the gastrointestinal tract and reduce the tissue-associated HIV viral levels.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Francesca Cossarini, MD; Phone Number: 212-659-9269; Email: francesca.cossarini@mountsinai.org
• Study Contact Backup: Name: Saurabh Mehandru, MD; Phone Number: 212-659-9206; Email: Saurabh.mehandru@mssm.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
      • Contact: Francesca Cossarini, MD; Phone Number: 212-659-9269; Email: francesca.cossarini@mountsinai.org
      • Contact: Saurabh Mehandru, MD; Phone Number: 212-659-9206; Email: Saurabh.mehandru@mssm.edu
      • Principal Investigator: Francesca Cossarini

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and lifestyle considerations and availability for the duration of the study
• Males and females; Age 18-75
• Chronic HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load
• Receiving treatment with a molecule with the potential for HIV cure
• Willingness and ability to undergo colonoscopy twice during the study timeframe

Exclusion Criteria:

• Known coagulopathy or altered coagulation studies
• Concomitant pregnancy of plans for pregnancy during the study period
• Concomitant Inflammatory Bowel Disease, Diarrheal disease or other gastrointestinal disease that might alter the intestinal mucosal tissue
• Concomitant sexually transmitted infection
• Any other condition which in the opinion of investigators would impede competence, compliance or possibly hinder completion of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with HIV Therapy; Subjects receiving therapies with the potential for HIV cure	Procedure: Colonoscopy; Colonoscopy is a procedure where an instrument called colonoscope is inserted through the rectum to look at the entire internal surface of the intestine. Participants will be placed on a stretcher on the left side. A colonoscope will be advanced into the colon and into the terminal ileum. The entire procedure should take approximately 40 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HIV tissue viral load	Change in HIV in tissue-associated HIV RNA viral load at the end of the study at month one compared to baseline	End of the study (at month one) compared to baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in number of Cytotoxic T cells	Change in number of tissue-associated cytotoxic T cells at the end of the study (at month one) period compared to baseline	End of the study (at month one) compared to baseline
Change in number of NK Cells	Change in number of tissue-associated NK cells at the end of the study (at month one) period compared to baseline	End of the study (at month one) compared to baseline

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Francesca Cossarini, MD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: December 7, 2022
• First Submitted That Met QC Criteria: December 7, 2022
• First Posted (Actual): December 15, 2022

Study Record Updates

• Last Update Posted (Actual): July 4, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Pathologic Processes; Disease Attributes; Immune System Diseases; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Infections; Communicable Diseases
• Other Study ID Numbers: STUDY-22-01294

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IPD at this time.

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