HIV InfectionNCT02707926
The Lymphoid Tissue Pharmacology of Antiretroviral Drugs
An observational study of HIV Infection, run by University of Nebraska.
Trial summary
Hypothesis: Antiretroviral drugs (ARVs) with enhanced LT penetration characteristics in vitro and in macaques will translate into an ARV regimen with increased LN and GALT concentrations and a faster decay and more potent suppression of HIV replication in LT in HIV-infected persons. Objectives: 1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection
- What is being tested?
- Anti-HIV Agents
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 25 Mar 2023to 17 Aug 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: Eighteen (18) antiretroviral drug (ARV)-naive, HIV-infected persons who are going to initiate ARV therapy will be recruited at the University of Minnesota. Study entry is open to adults regardless of race or ethnic background. While there will be every effort to seek out and include minority participants from both genders, the patient population is expected to be no different than that of the HIV infected population in Minnesota.
Who may be able to join
- Antiretroviral drug (ARV)-naive, HIV-infected individuals
- Aged 18 years or over
- Agree to initiating ARV therapy
- BMI ≤ 30
- Inguinal lymph node(s) identifiable by ultrasound at enrollment
- Screening plasma HIV RNA > 40,000 copies/mL
Show all 10Show fewer
- Screening CD4 count > 200 cells/mm3
- Women of child bearing potential must agree to use effective contraception while on the study.
- Screening viral isolates demonstrate genotype sensitivity to chosen antiretroviral therapy (ART) regimen.
- Able to provide voluntary written consent
Who cannot join
- Previous ARV therapy
- Contraindications to ARV regimen (e.g., comorbid conditions or drug interactions), or study procedures as determined by the principal investigator.
- 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
About this study
Hypothesis:
Antiretroviral drugs (ARVs) with enhanced LT penetration characteristics in vitro and in macaques will translate into an ARV regimen with increased LN and GALT concentrations and a faster decay and more potent suppression of HIV replication in LT in HIV-infected persons.
Objectives:
- Determine lymph nodes (LN) and gut-associated lymphoid tissue (GALT) pharmacokinetics (PK) in HIV-infected persons on an antiretroviral drug (ARV) regimen.
- Determine virological responses of antiretroviral therapy in plasma, peripheral blood mononuclear cells (PBMCs) and lymphoid tissue (LT).
Read the detailed description
This is a single-center study of 18 ARV naïve, HIV infected persons to assess impact of an ARV regimen on lymph node (LN) and (GALT) virus reservoirs.
All participants will give informed consent. At baseline, plasma and PBMCs will be obtained and all subjects will have an incisional biopsy of an inguinal LN and pinch biopsy of ileum and rectum via colonoscopy. The selected LT-enhanced ARV regimen will be initiated. Participants will return to the clinic at weeks 2 and 4 and then monthly for safety evaluations, CD4 T cell counts, plasma HIV-RNA and ARV drug concentrations in plasma and PBMCs. An intensive PK study will be performed at week 2. At months 3 and 6, the inguinal LN biopsy and pinch biopsies of ileum and rectum will be repeated.
- Conditions
- HIV Infection
- Being tested
- Anti-HIV Agents
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-HIV AgentsDrug
Also called antiretroviral (ARV) HIV drugs
Therapy to treat HIV infection
What is being measured
The primary outcome is the main question the study is designed to answer.
Lymph node (LN) tissue penetration ratio.
Ratio of antiretroviral drug concentration in lymph node (LN) to peripheral blood mononuclear cells (PBMCs)
Measured: 6 months
Lymph node (LN) residual viremia.
Quantification of residual viremia in lymph node (LN) at 6 months of therapy as measured by digital droplet polymerase chain reaction (PCR), which can quantify as low as 50 copies/million cells.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2016 (estimated)
- Study start25 Mar 2023
- Primary completion17 Aug 2023
- Study completion17 Aug 2023
Why it stopped: COVID-19 required halting recruitment into new clinical protocols. Following the allowed opening to clinical research, our assessment of site and investigator interest and time frame of available grant funding resulted in a judgment of futility.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe 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 Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tim Schacker, MD, Principal investigator, University of MinnesotaCourtney V Fletcher, PharmD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02707926
- Sponsor's protocol ID
- 0212-16-ET
- Other IDs
- 1R01AI124965-01
- Status last verified
- Aug 2023
- First submitted
- 3 Mar 2016
- Last updated
- 24 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: The results of this trial will be of interest to the HIV research and medical communities. We expect to submit the data from the main analysis within 6 months of completing the work. We will publish the results in a major scientific journal and present the results at a major scientific meeting (e.g., CROI). Subsequent analyses will be presented at national and international HIV meetings. Data generated under this project, and any intellectual property, will be administered in accordance with NIH policies, including the NIH Data Sharing Policy the NIH Public Access Policy.
Publications
Lorenzo-Redondo R, Fryer HR, Bedford T, Kim EY, Archer J, Pond SLK, Chung YS, Penugonda S, Chipman J, Fletcher CV, Schacker TW, Malim MH, Rambaut A, Haase AT, McLean AR, Wolinsky SM. Persistent HIV-1 replication maintains the tissue reservoir during therapy. Nature. 2016 Feb 4;530(7588):51-56. doi: 10.1038/nature16933. Epub 2016 Jan 27.
PubMed 26814962Fletcher CV, Staskus K, Wietgrefe SW, Rothenberger M, Reilly C, Chipman JG, Beilman GJ, Khoruts A, Thorkelson A, Schmidt TE, Anderson J, Perkey K, Stevenson M, Perelson AS, Douek DC, Haase AT, Schacker TW. Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2307-12. doi: 10.1073/pnas.1318249111. Epub 2014 Jan 27.
PubMed 24469825
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Lymphoid Tissue Pharmacology of Antiretroviral Drugs
- ClinicalTrials.gov ID
- NCT02707926
- Acronym / sponsor ID
- 0212-16-ET
- Conditions
- HIV Infection
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: COVID-19 required halting recruitment into new clinical protocols. Following the allowed opening to clinical research, our assessment of site and investigator interest and time frame of available grant funding resulted in a judgment of futility.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- University of Minnesota, National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- 25 Mar 2023 (actual)
- Primary completion
- 17 Aug 2023 (actual)
- Study completion
- 17 Aug 2023 (actual)
- First posted
- 14 Mar 2016 (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.
Hypothesis:
Antiretroviral drugs (ARVs) with enhanced LT penetration characteristics in vitro and in macaques will translate into an ARV regimen with increased LN and GALT concentrations and a faster decay and more potent suppression of HIV replication in LT in HIV-infected persons.
Objectives:
- Determine lymph nodes (LN) and gut-associated lymphoid tissue (GALT) pharmacokinetics (PK) in HIV-infected persons on an antiretroviral drug (ARV) regimen.
- Determine virological responses of antiretroviral therapy in plasma, peripheral blood mononuclear cells (PBMCs) and lymphoid tissue (LT).
Detailed description
This is a single-center study of 18 ARV naïve, HIV infected persons to assess impact of an ARV regimen on lymph node (LN) and (GALT) virus reservoirs.
All participants will give informed consent. At baseline, plasma and PBMCs will be obtained and all subjects will have an incisional biopsy of an inguinal LN and pinch biopsy of ileum and rectum via colonoscopy. The selected LT-enhanced ARV regimen will be initiated. Participants will return to the clinic at weeks 2 and 4 and then monthly for safety evaluations, CD4 T cell counts, plasma HIV-RNA and ARV drug concentrations in plasma and PBMCs. An intensive PK study will be performed at week 2. At months 3 and 6, the inguinal LN biopsy and pinch biopsies of ileum and rectum will be repeated.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Eighteen (18) antiretroviral drug (ARV)-naive, HIV-infected persons who are going to initiate ARV therapy will be recruited at the University of Minnesota. Study entry is open to adults regardless of race or ethnic background. While there will be every effort to seek out and include minority participants from both genders, the patient population is expected to be no different than that of the HIV infected population in Minnesota.
Key inclusion criteria (10 listed)
- Antiretroviral drug (ARV)-naive, HIV-infected individuals
- Aged 18 years or over
- Agree to initiating ARV therapy
- BMI ≤ 30
- Inguinal lymph node(s) identifiable by ultrasound at enrollment
Key exclusion criteria (5 listed)
- Previous ARV therapy
- Contraindications to ARV regimen (e.g., comorbid conditions or drug interactions), or study procedures as determined by the principal investigator.
- 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 |
|---|---|---|
| Anti-HIV AgentsAlso: antiretroviral (ARV) HIV drugsTherapy to treat HIV infection | Drug | – |
Primary outcome
Lymph node (LN) tissue penetration ratio.
Time frame: 6 months
Ratio of antiretroviral drug concentration in lymph node (LN) to peripheral blood mononuclear cells (PBMCs)
Lymph node (LN) residual viremia.
Time frame: 6 months
Quantification of residual viremia in lymph node (LN) at 6 months of therapy as measured by digital droplet polymerase chain reaction (PCR), which can quantify as low as 50 copies/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 24 Aug 2023.
- Background: PubMed 26814962Lorenzo-Redondo R, Fryer HR, Bedford T, Kim EY, Archer J, Pond SLK, Chung YS, Penugonda S, Chipman J, Fletcher CV, Schacker TW, Malim MH, Rambaut A, Haase AT, McLean AR, Wolinsky SM. Persistent HIV-1 replication maintains the tissue reservoir during therapy. Nature. 2016 Feb 4;530(7588):51-56. doi: 10.1038/nature16933. Epub 2016 Jan 27.
- Background: PubMed 24469825Fletcher CV, Staskus K, Wietgrefe SW, Rothenberger M, Reilly C, Chipman JG, Beilman GJ, Khoruts A, Thorkelson A, Schmidt TE, Anderson J, Perkey K, Stevenson M, Perelson AS, Douek DC, Haase AT, Schacker TW. Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2307-12. doi: 10.1073/pnas.1318249111. Epub 2014 Jan 27.
- Individual participant dataSharing planned: Yes. The results of this trial will be of interest to the HIV research and medical communities. We expect to submit the data from the main analysis within 6 months of completing the work. We will publish the results in a major scientific journal and present the results at a major scientific meeting (e.g., CROI). Subsequent analyses will be presented at national and international HIV meetings. Data generated under this project, and any intellectual property, will be administered in accordance with NIH policies, including the NIH Data Sharing Policy the NIH Public Access Policy.
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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.
Tim Schacker, MD principal investigator
University of Minnesota
Courtney V Fletcher, PharmD principal investigator
University of Nebraska
Questions about this trial
What is this clinical trial studying?
An observational study of HIV Infection, run by University of Nebraska.
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 10 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: withdrawn, as of the sponsor's last update on 24 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
Lymph node (LN) tissue penetration ratio. (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02707926, which also lists 2 linked publications.
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 24 Aug 2023.