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T-cell Responses to Concurrent HIV and Herpesvirus Infections

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03996018
Recruitment Status : Recruiting
First Posted : June 24, 2019
Last Update Posted : August 7, 2019
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Brief 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.

Condition or disease Intervention/treatment
HIV HIV Infections Other: T-cell lymphocyte responses

Detailed 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.

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Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: T-cell Responses to Concurrent HIV and Herpesvirus Infections
Actual Study Start Date : June 19, 2019
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : June 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Group/Cohort Intervention/treatment
group 1(HIV Uninfected)
Participant is HIV negative per antibody screen conducted on premises and participant is enrolled on HPTN 083 study
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).

group 2 (HIV Infected)
Participant has initiated ART therapy as a patient at St Jude Children's Research Hospital, newly diagnosed HIV and prolonged HIV
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).




Primary Outcome Measures :
  1. HIV-1 specific TCR repertoire: Change in Simpson's diversity index over time [ Time Frame: 0, 6, 12 and 18 months (+/- 30 days for all time points after 0). ]
    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].


Secondary Outcome Measures :
  1. Herpesvirus specific TCR repertoire: Change in Simpson's diversity index [ Time Frame: 0, 6, 12 and 18 months (+/- 30 days for all time points after 0). ]
    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].

  2. T-Cell exhaustion: binary value (Exhausted/not exhausted) [ Time Frame: 0, 6, 12 and 18 months (+/- 30 days for all time points after 0 ]
    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.

  3. HIV control: HIV viral load [ Time Frame: 0, 6, 12 and 18 months (+/- 30 days for all time points after 0 ]
    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.

  4. Presence of herpesvirus infections: IgM and IgG levels [ Time Frame: 0, 6, 12 and 18 months (+/- 30 days for all time points after 0 ]
    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).

  5. HLA typing [ Time Frame: baseline ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Adults with HIV who meet eligibility criteria.
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03996018


Contacts
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Contact: Amanda Green, MD 866-278-5833 referralinfo@stjude.org

Locations
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United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Amanda Green, MD    866-278-5833    referralinfo@stjude.org   
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
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Principal Investigator: Amanda Green, MD St. Jude Children's Research Hospital
Additional Information:
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Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT03996018    
Other Study ID Numbers: TORCH
First Posted: June 24, 2019    Key Record Dates
Last Update Posted: August 7, 2019
Last Verified: August 2019
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Herpesviridae Infections
Virus Diseases
DNA Virus Infections