- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02707926
The Lymphoid Tissue Pharmacology of Antiretroviral Drugs
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).
Study Overview
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 Type
Contacts and Locations
Study Contact
- Name: Tim Schacker, MD
- Phone Number: 612-624-9955
- Email: schac008@umn.edu
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
6 months
|
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.
|
6 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Courtney V Fletcher, PharmD, University of Nebraska
- Principal Investigator: Tim Schacker, MD, University of Minnesota
Publications and helpful links
General 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.
- Fletcher 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Urogenital Diseases
- Genital Diseases
- HIV Infections
- Anti-Infective Agents
- Antiviral Agents
- Anti-Retroviral Agents
- Anti-HIV Agents
Other Study ID Numbers
- 0212-16-ET
- 1R01AI124965-01 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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