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.

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).

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.

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

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.

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.

6 months of completing the work

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.