Clinical trial NCT05652088: The Role of the Gastrointestinal-associated Lymphoid Tissue in the Cure of HIV Infection
Official title: The Role of the Gastrointestinal-associated Lymphoid Tissue in the Cure of HIV Infection
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: HIV Infection
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2022-12-15
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All subjects receiving therapies with the potential for HIV cure who agree to participate in this study, will undergo a colonoscopy to obtain tissue samples for research assays before and after receiving such treatment.
Primary purpose: BASIC_SCIENCE

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in HIV tissue viral load
timeFrame: End of the study (at month one) compared to baseline
Secondary outcomes:
measure: Change in number of Cytotoxic T cells
timeFrame: End of the study (at month one) compared to baseline
measure: Change in number of NK Cells
timeFrame: End of the study (at month one) compared to baseline
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Francesca Cossarini, MD
role: PRINCIPAL_INVESTIGATOR
References: