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Predictors of Time to Viremia With an Analytic Treatment Interruption

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ClinicalTrials.gov Identifier: NCT03033017
Recruitment Status : Withdrawn (Funding c hange)
First Posted : January 26, 2017
Last Update Posted : December 4, 2017
Sponsor:
Information provided by (Responsible Party):
University of Minnesota

Brief 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).


Condition or disease Intervention/treatment
HIV Other: Blood Testing

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.

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Study Type : Observational
Actual Enrollment : 0 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Predictors of Time to Viremia With an Analytic Treatment Interruption
Study Start Date : July 2016
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Group/Cohort Intervention/treatment
HIV-infected on antiretroviral therapy 2 years
HIV-infected participants who have been on antiretroviral therapy (ART) for at least two years.
Other: Blood Testing



Primary Outcome Measures :
  1. Time to viremia [ Time Frame: Baseline to 14 days ]
    Time to viremia

  2. 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

  3. SCA (Single Copy Assay) [ Time Frame: Baseline to 14 days ]
    performed as described in the protocol and reported as number of cells/ml plasma.

  4. 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

  5. Change in CD4 [ Time Frame: Baseline to 14 days ]
  6. Change in CD4/CD8 ratio [ Time Frame: Baseline to 14 days ]
  7. Polyadenylation-RT-ddPCR assay for total transcripts (TAR) [ Time Frame: Baseline to 14 days ]
    transcripts/million cells

  8. ddPCR assays for read-through, elongated, polyadenylated, and multiply-spliced (Tat-Rev) transcripts [ Time Frame: Baseline to 14 days ]
    reported as transcripts/million cells


Biospecimen Retention:   Samples With DNA
Lymph node biopsy: Inguinal lymph node biopsies will be collected per institutional guidelines


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 to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
30 HIV-infected participants who have been on antiretroviral therapy (ART) for at least two years.
Criteria

Inclusion Criteria:

  1. HIV-infected individuals who have been on ART therapy for at least two years
  2. Male or Female, aged 18 years or older
  3. Documented evidence of CD4+ T cell count ≥ 300 cells/µl for 12 months prior to study entry
  4. BMI ≤ 30 or evidence by ultrasound or physical exam of peripheral inguinal lymph node(s) that is/are surgically accessible
  5. 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)
  6. 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.
  7. Women of child bearing potential and men with partners of child bearing potential must agree to use effective contraception during protocol
  8. Able to provide voluntary written consent.

Exclusion Criteria

  1. ART was initiated during acute infection (within first 6 months of infection)
  2. Planning or current pregnancy or breastfeeding
  3. 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.
  4. Inability to comply with study procedures per enrolling physician discretion.

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): NCT03033017


Locations
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United States, California
University of California
San Francisco, California, United States
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
University of Minnesota
Investigators
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Principal Investigator: Timothy Schacker, MD University of Minnesota
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Responsible Party: University of Minnesota
ClinicalTrials.gov Identifier: NCT03033017    
Other Study ID Numbers: 24777
First Posted: January 26, 2017    Key Record Dates
Last Update Posted: December 4, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by University of Minnesota:
HIV
Additional relevant MeSH terms:
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Viremia
Virus Diseases
Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes