HIVNCT03033017
Predictors of Time to Viremia With an Analytic Treatment Interruption
An observational study of HIV, run by University of Minnesota at 2 sites in United States.
Trial summary
This is a two-center study of 30 HIV-infected participants who have been on antiretroviral therapy (ART) for at least two years. Participants will be asked to undergo LN and GALT biopsies both before and after a closely monitored analytic treatment interruption (ATI). Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- HIV
- What is being tested?
- Blood Testing
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2016to Jan 2019
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 30 HIV-infected participants who have been on antiretroviral therapy (ART) for at least two years.
Who may be able to join
- HIV-infected individuals who have been on ART therapy for at least two years
- Male or Female, aged 18 years or older
- Documented evidence of CD4+ T cell count ≥ 300 cells/µl for 12 months prior to study entry
- BMI ≤ 30 or evidence by ultrasound or physical exam of peripheral inguinal lymph node(s) that is/are surgically accessible
- Documented plasma HIV RNA levels below level of quantification <20 to <40 copies RNA/mL depending on the assay) ≥ 24 months (a single measurement above the level of detection but < 200 copies/ml will be allowed)
- Willing to switch to an ART regimen consisting of dolutegravir and either tenofovir/emtricitabine or abacavir/lamivudine to avoid drugs with a long-half life that would expose the participant to a period of mono-therapy when the drugs are stopped.
- Women of child bearing potential and men with partners of child bearing potential must agree to use effective contraception during protocol
- Able to provide voluntary written consent.
Who cannot join
- ART was initiated during acute infection (within first 6 months of infection)
- Planning or current pregnancy or breastfeeding
- History and/or presence of any clinically significant disease or disorder, such as cardiovascular, pulmonary, renal, hepatic, neurological, gastrointestinal and psychiatric/mental disease/disorder, which, in the opinion of the enrolling physician, may put the participant at risk because of participation in the study, influence the results of the study, or affect the participant's ability to participate in the study.
- Inability to comply with study procedures per enrolling physician discretion.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Minnesota
Minneapolis, Minnesota, 55455
University of California
San Francisco, California
About this study
This is a two-center study of 30 HIV-infected participants who have been on antiretroviral therapy (ART) for at least two years.
Participants will be asked to undergo LN and GALT biopsies both before and after a closely monitored analytic treatment interruption (ATI).
Read the detailed description
The HIV field has made a dramatic shift to an emphasis on finding a cure for HIV.
However, there is no agreed upon test of cure, or even what the definition of a cure might be. The investigator believes the most reliable test of cure will be an analytic treatment interruption (ATI) with time to viremia as a standard measure of the impact of an intervention on the degree to which the reservoir has been depleted. This is rational as modeling studies utilizing ATI data point to reservoir size as an important predictor of time to viremia(1) and other studies have shown that levels of HIV DNA(2) and cell associated HIV RNA(3) prior to starting antiretroviral therapy (ART) are associated with time-to-rebound. However, these studies used a limited sampling strategy to determine when viremia rebounded and it is likely that greater sensitivity in measures of time-to rebound will be needed to accurately assess the impact of an intervention. The investigators have tested an ATI strategy where plasma HIV is sampled three times each week and ART is resumed once the virus becomes detectable. In this small, pilot study, the investigators sampled lymph nodes, GALT, plasma, and PBMC before, during, and after the ATI and found the time-to-rebound was 14 days (range 5 to 30 days) and that total years of ART exposure was associated with the time-to-rebound (4). The investigators propose a similar study that includes more intensive blood and lymphoid tissue sampling to identify factors that predict time to-rebound to provide a necessary foundation for future studies that utilize a treatment interruption as a test of efficacy for curative interventions.
- Conditions
- HIV
- Being tested
- Blood Testing
- Keywords
- HIV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood TestingOther
| Study group | Role | What they receive |
|---|---|---|
| HIV-infected on antiretroviral therapy 2 years | HIV-infected participants who have been on antiretroviral therapy (ART) for at least two years. Receives: Other: Blood Testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to viremia
Time to viremia
Measured: Baseline to 14 days
Change in vRNA+ and vDNA+ cells
measured by in situ hybridization and using quantitative image analysis to determine the frequency of + cell/gram lymphoid tissue
Measured: Baseline to 14 days
SCA (Single Copy Assay)
performed as described in the protocol and reported as number of cells/ml plasma.
Measured: Baseline to 14 days
Change in markers of immune activation
All measurements are the same IL1B, TNF, IL4, IL13, IL17, IL21,IL22, IL6, IL10
Measured: Baseline to 14 days
Change in CD4
Measured: Baseline to 14 days
Change in CD4/CD8 ratio
Measured: Baseline to 14 days
Polyadenylation-RT-ddPCR assay for total transcripts (TAR)
transcripts/million cells
Measured: Baseline to 14 days
ddPCR assays for read-through, elongated, polyadenylated, and multiply-spliced (Tat-Rev) transcripts
reported as transcripts/million cells
Measured: Baseline to 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2017 (estimated)
- Study startJul 2016
- Primary completionJan 2019 (estimated)
- Study completionJan 2019 (estimated)
Why it stopped: Funding c hange
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 University of MinnesotaThe 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Timothy Schacker, MD, Principal investigator, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03033017
- Sponsor's protocol ID
- 24777
- Status last verified
- Dec 2017
- First submitted
- 7 Oct 2016
- Last updated
- 4 Dec 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predictors of Time to Viremia With an Analytic Treatment Interruption
- ClinicalTrials.gov ID
- NCT03033017
- Acronym / sponsor ID
- 24777
- Conditions
- HIV
- Keywords
- HIV
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: Funding c hange
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Study start
- Jul 2016
- Primary completion
- Jan 2019 (estimated)
- Study completion
- Jan 2019 (estimated)
- First posted
- 26 Jan 2017 (estimated)
- 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 two-center study of 30 HIV-infected participants who have been on antiretroviral therapy (ART) for at least two years.
Participants will be asked to undergo LN and GALT biopsies both before and after a closely monitored analytic treatment interruption (ATI).
Detailed description
The HIV field has made a dramatic shift to an emphasis on finding a cure for HIV.
However, there is no agreed upon test of cure, or even what the definition of a cure might be. The investigator believes the most reliable test of cure will be an analytic treatment interruption (ATI) with time to viremia as a standard measure of the impact of an intervention on the degree to which the reservoir has been depleted. This is rational as modeling studies utilizing ATI data point to reservoir size as an important predictor of time to viremia(1) and other studies have shown that levels of HIV DNA(2) and cell associated HIV RNA(3) prior to starting antiretroviral therapy (ART) are associated with time-to-rebound. However, these studies used a limited sampling strategy to determine when viremia rebounded and it is likely that greater sensitivity in measures of time-to rebound will be needed to accurately assess the impact of an intervention. The investigators have tested an ATI strategy where plasma HIV is sampled three times each week and ART is resumed once the virus becomes detectable. In this small, pilot study, the investigators sampled lymph nodes, GALT, plasma, and PBMC before, during, and after the ATI and found the time-to-rebound was 14 days (range 5 to 30 days) and that total years of ART exposure was associated with the time-to-rebound (4). The investigators propose a similar study that includes more intensive blood and lymphoid tissue sampling to identify factors that predict time to-rebound to provide a necessary foundation for future studies that utilize a treatment interruption as a test of efficacy for curative interventions.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HIV-infected on antiretroviral therapy 2 years | – | Other: Blood TestingHIV-infected participants who have been on antiretroviral therapy (ART) for at least two years. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 30 HIV-infected participants who have been on antiretroviral therapy (ART) for at least two years.
Key inclusion criteria (8 listed)
- HIV-infected individuals who have been on ART therapy for at least two years
- Male or Female, aged 18 years or older
- Documented evidence of CD4+ T cell count ≥ 300 cells/µl for 12 months prior to study entry
- BMI ≤ 30 or evidence by ultrasound or physical exam of peripheral inguinal lymph node(s) that is/are surgically accessible
- Documented plasma HIV RNA levels below level of quantification <20 to <40 copies RNA/mL depending on the assay) ≥ 24 months (a single measurement above the level of detection but < 200 copies/ml will be allowed)
Key exclusion criteria (4 listed)
- ART was initiated during acute infection (within first 6 months of infection)
- Planning or current pregnancy or breastfeeding
- History and/or presence of any clinically significant disease or disorder, such as cardiovascular, pulmonary, renal, hepatic, neurological, gastrointestinal and psychiatric/mental disease/disorder, which, in the opinion of the enrolling physician, may put the participant at risk because of participation in the study, influence the results of the study, or affect the participant's ability to participate in the study.
- Inability to comply with study procedures per enrolling physician discretion.
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 |
|---|---|---|
| Blood Testing | Other | HIV-infected on antiretroviral therapy 2 years |
Primary outcome
Time to viremia
Time frame: Baseline to 14 days
Time to viremia
Change in vRNA+ and vDNA+ cells
Time frame: Baseline to 14 days
measured by in situ hybridization and using quantitative image analysis to determine the frequency of + cell/gram lymphoid tissue
SCA (Single Copy Assay)
Time frame: Baseline to 14 days
performed as described in the protocol and reported as number of cells/ml plasma.
Change in markers of immune activation
Time frame: Baseline to 14 days
All measurements are the same IL1B, TNF, IL4, IL13, IL17, IL21,IL22, IL6, IL10
Change in CD4
Time frame: Baseline to 14 days
Change in CD4/CD8 ratio
Time frame: Baseline to 14 days
Polyadenylation-RT-ddPCR assay for total transcripts (TAR)
Time frame: Baseline to 14 days
transcripts/million cells
ddPCR assays for read-through, elongated, polyadenylated, and multiply-spliced (Tat-Rev) transcripts
Time frame: Baseline to 14 days
reported as transcripts/million cells
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2017.
- Individual participant dataSharing planned: Undecided
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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.
Timothy Schacker, MD principal investigator
University of Minnesota
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV, run by University of Minnesota at 2 sites 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 8 inclusion and 4 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: withdrawn, as of the sponsor's last update on 4 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 was withdrawn before enrolling participants, so there are no results.
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?
Time to viremia (time frame: Baseline to 14 days). The study lists 8 primary outcomes in all. 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 4 Dec 2017.