T-cell Responses to Concurrent HIV and Herpesvirus Infections

HIV Infections Clinical Trial

Official title:

T-cell Responses to Concurrent HIV and Herpesvirus Infections

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03996018
• Other study ID #: TORCH
• Status: Active, not recruiting
• Start date: June 19, 2019
• Est. completion date: December 31, 2026

Study information

• Verified date: September 2023
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a research study in which we are trying to discover new information about how HIV and herpes viruses interact with the immune system. The goal of the study is to learn more about how T-cells in your immune system respond to and fight off long-term (chronic) viruses, in order to improve medical care in the future.

Description:

HIV-uninfected & HIV-infected participants who enroll on this study will be asked to provide blood samples for 18 months. These samples will be used to assess T-cell responses and presence of herpesvirus(es).

Primary Objective

Characterize phenotypic and functional features, including TCR repertoires of HIV-specific CD8 T-cell responses and exhaustion in HIV-positive humans with and without concomitant herpesvirus infections.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 135
• Est. completion date: December 31, 2026
• Est. primary completion date: July 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Criteria • Participant is greater than or equal to 18 years of age.

Group 1 (HIV Uninfected) Only

• Participant is HIV negative per antibody screen conducted on premises

• Participant is enrolled on HPTN 083 study (receiving HIV-PrEP) (see Recruitment and Screening).

Group 2 (HIV Infected) Only

• Participant has initiated ART therapy as a patient at St Jude Children's Research Hospital

*Note: participants will be allowed to continue on study and have data analyzed regardless of presence of detectable HIV or CD4+ counts.

a) Newly diagnosed HIV

• Participant is HIV-1 positive per medical record documentation or positive antibody screen conducted on premises, with initial diagnosis within 90 days prior to enrollment

b) Prolonged HIV

• Participant is HIV-1 positive per medical record documentation or positive antibody screen conducted on premises, with initial diagnosis more than 365 days prior to enrollment

Exclusion Criteria:

• Participant is unable or unwilling to provide informed consent.

• If female of child bearing potential, participant has a positive urine pregnancy test at screening. Note: if participant becomes pregnant while on study, they may not continue on study.

• Concurrent enrollment on a research study or receiving treatment for concurrent medical diagnosis with any of the following interventions which may impact study outcomes: high dose or prolonged steroids, chemotherapy to treat malignancy, radiation therapy, biologic pharmaceutical treatments that induce immunosuppression.

• If in the opinion of the investigator, participation in the blood draw would endanger the health of the participant.

• Participant is enrolled in other clinical trials that include any blood sampling such that the cumulative blood draws would exceed that established as constituting minimal risk (e.g., more than 550 ml in an 8 week period with collection more frequently than 2 times per week).

Related Conditions & MeSH terms

• Communicable Diseases
• Herpesviridae Infections
• HIV
• HIV Infections
• Infections

Intervention

Other:
• T-cell lymphocyte responses
T-cell lymphocyte responses to human immunodeficiency virus (HIV) with and without concomitant herpesvirus infections (specifically, the persistence of HIV-specific human CD8 T-cells in the context of antiretroviral therapy (ART).

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HIV-1 specific TCR repertoire: Change in Simpson's diversity index over time	using separated PBMCs, HIV-1 specific T-cells will be labeled with major histocompatibility complex (MHC) I tetramers previously described to be specific for HIV-1 [14-18]. Labeled cells will be subjected to flow cytometry for identity confirmation via established antibody cell marker staining, counting and sorting into single cells. The TCR genes of the individually sorted HIV-1 tetramer positive T-cells will then be sequenced, establishing a repertoire of TCR sequences. Diversities of the TCR gene repertoires obtained from each study group will be assessed using the established algorithm for Simpson's diversity index [9].	0, 6, 12 and 18 months (+/- 30 days for all time points after 0).
Secondary	Herpesvirus specific TCR repertoire: Change in Simpson's diversity index	process as described above, with use of newly identified and previously published herpesvirus specific MHC I tetramers, including those for HSV-1, HSV-2, EBV and CMV, [19-25]. Comparisons of TCR repertoires will be made between newly acquired and latent herpesvirus infections. Diversities of the TCR gene repertoires obtained from each study group will be assessed using the established algorithm for Simpson's diversity index [9].	0, 6, 12 and 18 months (+/- 30 days for all time points after 0).
Secondary	T-Cell exhaustion: binary value (Exhausted/not exhausted)	Intracellular and cell surface proteins will be assessed to determine if T-cells that have entered the exhaustion pathway. These markers include, but are not limited to, PD-1, Tim3, Tcf7, Tbet, and Tox. Marker expression will be measured at the transcript or protein level [1, 2]; T-cells will be concomitantly labeled/detected with T-cell specific markers and HIV-1 MHC I tetramers to confirm identity. Using this information, a binary value of "exhausted' or "not exhausted" will be assigned.	0, 6, 12 and 18 months (+/- 30 days for all time points after 0
Secondary	HIV control: HIV viral load	presence (or lack of) of HIV infection will be determined by HIV antigen/antibody testing. Control will be assessed by CD4+ T-cell counts, HIV viral titers, infections acquired likely due to immunodeficiency. The main outcome measure will be viral load. HIV related laboratory results including HIV screen, viral titers, T-cell counts will all be disclosed to patients as per standard of care.	0, 6, 12 and 18 months (+/- 30 days for all time points after 0
Secondary	Presence of herpesvirus infections: IgM and IgG levels	at first visit, all patients will have IgM and IgG levels in the clinical laboratory for each named virus to establish presence of chronic vs. newly acquired herpesvirus infections. At each visit all patients will have serological testing via HSV-1, HSV-2, CMV, EBV and specific IgG direct antibody detection with quantitative enzymatic immune assay (EIA). Patients with active mucosal (oral or genital) or skin lesions consistent with primary or secondary HSV infections will be swabbed and sent for PCR and/or direct fluorescence antibody assay (DFA) in the clinical laboratory. Control will be assessed by quantitative EIA results and frequency of herpesvirus specific symptoms of flare (acute or reactivated infections).	0, 6, 12 and 18 months (+/- 30 days for all time points after 0
Secondary	HLA typing	peripheral blood mononuclear cells (PBMCs) will be separated from patient's whole blood specimens. DNA will be extracted and specific HLA loci will be amplified using PCR, and yielded products will be sequenced. This will guide appropriate use of TCR tetramers.	baseline

External Links

•   Clinical Trials Open at St. Jude
•   St. Jude Children's Research Hospital