HIVNCT03996018
T-cell Responses to Concurrent HIV and Herpesvirus Infections
An observational study of HIV and HIV Infections, run by St. Jude Children's Research Hospital at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV, HIV Infections
- What is being tested?
- T-cell lymphocyte responses
- How many people
- 135 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Jun 2019to 28 Jul 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adults with HIV who meet eligibility criteria.
Who may be able to join
- 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
Show all 11Show fewer
- Note: participants will be allowed to continue on study and have data analyzed regardless of presence of detectable HIV or CD4+ counts.
- 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
- 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
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
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.
Read the 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.
- Conditions
- HIV, HIV Infections
- Being tested
- T-cell lymphocyte responses
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
T-cell lymphocyte responsesOther
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).
| Study group | Role | What they receive |
|---|---|---|
| group 1(HIV Uninfected) | Participant is HIV negative per antibody screen conducted on premises and participant is enrolled on HPTN 083 study Receives: Other: T-cell lymphocyte responses | |
| 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 Receives: Other: T-cell lymphocyte responses |
What is being measured
The primary outcome is the main question the study is designed to answer.
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].
Measured: 0, 6, 12 and 18 months (+/- 30 days for all time points after 0).
Secondary outcomes (5)
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].
Measured: 0, 6, 12 and 18 months (+/- 30 days for all time points after 0).
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.
Measured: 0, 6, 12 and 18 months (+/- 30 days for all time points after 0
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.
Measured: 0, 6, 12 and 18 months (+/- 30 days for all time points after 0
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).
Measured: 0, 6, 12 and 18 months (+/- 30 days for all time points after 0
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.
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2019
- Study start19 Jun 2019
- Primary completion28 Jul 2023
- Study completion28 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 135 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Amanda Green, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03996018
- Sponsor's protocol ID
- TORCH
- Status last verified
- Nov 2024
- First submitted
- 29 May 2019
- Last updated
- 15 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- T-cell Responses to Concurrent HIV and Herpesvirus Infections
- ClinicalTrials.gov ID
- NCT03996018
- Acronym / sponsor ID
- TORCH
- Conditions
- HIV, HIV Infections
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 135 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Study start
- 19 Jun 2019 (actual)
- Primary completion
- 28 Jul 2023 (actual)
- Study completion
- 28 Jul 2023 (actual)
- First posted
- 24 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| group 1(HIV Uninfected) | – | Other: T-cell lymphocyte responsesParticipant is HIV negative per antibody screen conducted on premises and participant is enrolled on HPTN 083 study |
| group 2 (HIV Infected) | – | Other: T-cell lymphocyte responsesParticipant has initiated ART therapy as a patient at St Jude Children's Research Hospital, newly diagnosed HIV and prolonged HIV |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults with HIV who meet eligibility criteria.
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (5 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| T-cell lymphocyte responsesT-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). | Other | group 1(HIV Uninfected), group 2 (HIV Infected) |
Primary outcome
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].
5 secondary outcomes
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).
T-Cell exhaustion: binary value (Exhausted/not exhausted)
Time frame: 0, 6, 12 and 18 months (+/- 30 days for all time points after 0
HIV control: HIV viral load
Time frame: 0, 6, 12 and 18 months (+/- 30 days for all time points after 0
Presence of herpesvirus infections: IgM and IgG levels
Time frame: 0, 6, 12 and 18 months (+/- 30 days for all time points after 0
HLA typing
Time frame: baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2024.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
Related trials for HIV
Not yet recruiting
HealthMpowerment Korea: Pilot Testing the Cultural Adaptation of a Digital HIV Intervention for Men Who Have Sex With Men in South Korea
HIV Infections, HIV Prevention and Care
Not yet recruiting
Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amanda Green, MD principal investigator
St. Jude Children's Research Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV and HIV Infections, run by St. Jude Children's Research Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2024.