The Lymphoid Tissue Pharmacology of Antiretroviral Drugs

Withdrawn

• Conditions: HIV Infection

• Registration Number: NCT02707926
• Lead Sponsor: University of Nebraska

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. Determine lymph nodes (LN) and gut-associated lymphoid tissue (GALT) pharmacokinetics (PK) in HIV-infected persons on an antiretroviral drug (ARV) regimen.

2. 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 Timeline

• Study First Submitted: 2016-03-03
• Study First Submitted QC: 2016-03-08
• Study First Posted: 2016-03-14
• Study Start: 2023-03-25
• Status Verified: 2023-08
• Primary Completion: 2023-08-17
• Study Completion: 2023-08-17
• Last Update Submitted: 2023-08-22
• Last Update Posted: 2023-08-24

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Antiretroviral drug (ARV)-naive, HIV-infected individuals
2. Aged 18 years or over
3. Agree to initiating ARV therapy
4. BMI ≤ 30
5. Inguinal lymph node(s) identifiable by ultrasound at enrollment
6. Screening plasma HIV RNA > 40,000 copies/mL
7. Screening CD4 count > 200 cells/mm3
8. Women of child bearing potential must agree to use effective contraception while on the study.
9. Screening viral isolates demonstrate genotype sensitivity to chosen antiretroviral therapy (ART) regimen.
10. Able to provide voluntary written consent

Exclusion Criteria

1. Previous ARV therapy
2. Contraindications to ARV regimen (e.g., comorbid conditions or drug interactions), or study procedures as determined by the principal investigator.
3. Planning or current pregnancy or breastfeeding
4. 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.
5. Inability to comply with study procedures per enrolling physician discretion

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Lymph node (LN) residual viremia.	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.
Lymph node (LN) tissue penetration ratio.	6 months	Ratio of antiretroviral drug concentration in lymph node (LN) to peripheral blood mononuclear cells (PBMCs)