The Lymphoid Tissue Pharmacology of Antiretroviral Drugs

NCT02707926 | Withdrawn

• 2 other identifiers: 0212-16-ET1R01AI124965-01
• Study Type: observational
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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. 1.Determine lymph nodes (LN) and gut-associated lymphoid tissue (GALT) pharmacokinetics (PK) in HIV-infected persons on an antiretroviral drug (ARV) regimen.
2. 2.Determine virological responses of antiretroviral therapy in plasma, peripheral blood mononuclear cells (PBMCs) and lymphoid tissue (LT).

Conditions

HIV Infection

Outcome Measures

Primary Outcomes (2)

• Lymph node (LN) tissue penetration ratio.

  Ratio of antiretroviral drug concentration in lymph node (LN) to peripheral blood mononuclear cells (PBMCs)

  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.

  6 months

Interventions

Anti-HIV Agents DRUG

Therapy to treat HIV infection

Also known as: antiretroviral (ARV) HIV drugs

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nebraska: lead
• University of Minnesota: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Related Publications (2)

• 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.

  PMID: 26814962 BACKGROUND

• 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.

  PMID: 24469825 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood, urine, lymph node biopsy, colonoscopy biopsy of ileum and rectum

MeSH Terms

Conditions

HIV Infections

Interventions

Anti-HIV Agents; Anti-Retroviral Agents

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antiviral Agents; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Tim Schacker, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

• Courtney V Fletcher, PharmD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2016
• First Posted: March 14, 2016
• Study Start: March 25, 2023
• Primary Completion: August 17, 2023
• Study Completion: August 17, 2023
• Last Updated: August 24, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: 6 months of completing the work
• Access Criteria: 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.