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

HIV Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05652088
• Other study ID #: STUDY-22-01294
• Status: Enrolling by invitation
• Phase: N/A
• Start date: March 14, 2023
• Est. completion date: June 2025

Study information

• Verified date: May 2024
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 6
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• HIV Infection
• HIV Infections
• Infections

Intervention

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

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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