Antiretroviral Localization in Gut-Associated Lymphoid Tissue and Lower Female Genital Tract Tissue of HIV+ Subjects

NCT02641444 | Terminated

• 1 other identifier: 15-2865
• Study Type: observational
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to find out how the drugs Truvada® (tenofovir/emtricitabine), Isentress® (raltegravir), Reyataz® (atazanavir), Sustiva® (efavirenz), and Selzentry® (maraviroc) get into the intestines and the female genital tract. All of these drugs are very effective at reducing the number of HIV viruses in the blood, however it is unknown how the drugs move around inside tissues where HIV might be hiding. This study will determine specifically where in the tissue the drug and the HIV are located through the use of a new technology that takes creates a picture of the tissue. This information will help scientists determine the best way to make new drugs to target the hidden HIV in tissue.

Conditions

HIV

Outcome Measures

Primary Outcomes (1)

• Antiretroviral tissue localization

  Tissues collected during inpatient stay will be frozen for later analysis (i.e. MSI-derived images of TFV, FTC, RAL, ATZ, EFV, and MVC localization within tissue slices.) to be completed within 6 months of tissue collection.

  Samples collected within 24 hours post-dose

Secondary Outcomes (4)

• Quantitation of antiretroviral tissue concentrations by LC-MS/MS

  Samples collected within 24 hours post-dose

• Immunohistochemical images of CD3, CD4, and CD8 distribution within tissue slices

  Samples collected within 24 hours post-dose

• in-situ hybridization images of HIV RNA distribution within tissue slices

  Samples collected within 24 hours post-dose

• Quantification of antiretroviral tissue concentrations by MSI

  Samples collected within 24 hours post-dose

Study Arms (4)

Efavirenz

Receiving efavirenz as part of their HIV regimen. Will undergo blood plasma collection, cervical and vaginal biopsy, and colonoscopy with ileal and rectal biopsy.

Procedure: Blood plasma collection; Procedure: Cervical and Vaginal Biopsy; Procedure: Colonoscopy with Ileal and Rectal Biopsy

Atazanavir

Receiving atazanavir as part of their HIV regimen. Will undergo blood plasma collection, cervical and vaginal biopsy, and colonoscopy with ileal and rectal biopsy.

Procedure: Blood plasma collection; Procedure: Cervical and Vaginal Biopsy; Procedure: Colonoscopy with Ileal and Rectal Biopsy

Raltegravir

Receiving raltegravir as part of their HIV regimen. Will undergo blood plasma collection, cervical and vaginal biopsy, and colonoscopy with ileal and rectal biopsy.

Procedure: Blood plasma collection; Procedure: Cervical and Vaginal Biopsy; Procedure: Colonoscopy with Ileal and Rectal Biopsy

Maraviroc

Receiving maraviroc as part of their HIV regimen. Will undergo blood plasma collection, cervical and vaginal biopsy, and colonoscopy with ileal and rectal biopsy.

Procedure: Blood plasma collection; Procedure: Cervical and Vaginal Biopsy; Procedure: Colonoscopy with Ileal and Rectal Biopsy

Interventions

Blood plasma collection PROCEDURE

Approximately 3mL of blood will be taken from each subject just prior to the colonoscopy.

Atazanavir; Efavirenz; Maraviroc; Raltegravir

Cervical and Vaginal Biopsy PROCEDURE

2 biopsies each will be collected from the vaginal wall and the cervix

Atazanavir; Efavirenz; Maraviroc; Raltegravir

Colonoscopy with Ileal and Rectal Biopsy PROCEDURE

10 biopsies each will be collected from the rectum and terminal ileum from each subject during the colonoscopy.

Atazanavir; Efavirenz; Maraviroc; Raltegravir

Eligibility Criteria

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

Study Population

This study will consist of 22 HIV positive women between 18-65 years of age (inclusive) with an intact gastrointestinal tract, uterus and cervix who are available to complete all study procedures at UNC.

You may qualify if:

• Healthy HIV-positive female subjects between the ages of 18 and 65 years, inclusive on the date of screening, with an intact gastrointestinal tract, uterus, and cervix. Healthy is defined as no clinically relevant abnormalities that would interfere with the interpretation of results, or pose unnecessary risk onto volunteers due to study procedures.
• All subjects must have an undetectable viral load at the time of screening or a documented undetectable viral load within the preceding 3 months of screening.
• All subjects must be receiving one of the study regimens as part of their regular HIV care for at least 6 months preceding the date of enrollment.
• Subjects must not have a history of GI disease (e.g. Crohn's disease, irritable bowel syndrome, ulcerative colitis, diverticulitis, colon cancer) or have a history of GI surgery.
• All subjects (of childbearing potential) must have a negative serum pregnancy test at screening and negative urine pregnancy tests on days of sampling and should be using at least one of the following methods of contraception from the screening visit through 72 hours prior to inpatient admission (at which time the women will be asked to remain abstinent until after their follow-up visit):
• Systemic hormonal contraceptive (oral, depot, transdermal or implant)
• IUD placed at least 1 month prior to study enrollment
• Bilateral tubal ligation (Sterilization)
• Vasectomized male partners
• Condom + Spermicide
• Engaged in sexual activity with female only sex partners or abstinent for at least 3 months prior with no intention of becoming sexually active during the study period. Any history of recent or present concomitant male sex partners will be addressed and ruled out in the context of screening participants for eligibility for the protocol
• Body Mass Index (BMI) of approximately 18 to 37 kg/m2; and a total body weight \> 45 kg (99 lbs).
• Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the trial.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
• Subject must have documentation of a normal pap smear within 36 months of the screening visit, no procedures for abnormal cervical/vaginal pathology in the last six months, at least one prior gynecological visit as part of subject's routine medical history.

You may not qualify if:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including documented drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
• Subjects with a history of hysterectomy or cervical resection that would preclude obtaining a cervical biopsy.
• Subjects who are pregnant, possibly pregnant or lactating.
• Subjects with a presence of abnormal vaginal discharge bleeding at screening.
• History of febrile illness within five days prior to enrollment.
• A positive urine drug screen for illicit substances (e.g. cocaine, methamphetamines) that would increase risk associated with sedation.
• Active Hepatitis B infection
• An untreated-positive test for syphilis, gonorrhea, Chlamydia, or trichomonas at screening. Tests for these STIs will be performed on samples from both the vaginal and rectal orifices.
• Any clinically significant laboratory chemistry or hematology result Grade 3 or greater according to the DAIDS Laboratory Grading Tables
• Treatment with an investigational drug within 4 months preceding the first dose of trial medication.
• History of regular alcohol consumption exceeding 14 drinks (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of spirits) per week.
• Participation in a clinical trial involving genital tract or rectal biopsies within 6 months preceding enrollment.
• Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing.
• History of sensitivity to heparin or heparin-induced thrombocytopenia.
• Allergy to lidocaine or Monsel's solution.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Related Publications (2)

• Thompson CG, Bokhart MT, Sykes C, Adamson L, Fedoriw Y, Luciw PA, Muddiman DC, Kashuba AD, Rosen EP. Mass spectrometry imaging reveals heterogeneous efavirenz distribution within putative HIV reservoirs. Antimicrob Agents Chemother. 2015 May;59(5):2944-8. doi: 10.1128/AAC.04952-14. Epub 2015 Mar 2.

  PMID: 25733502 BACKGROUND

• Robichaud G, Garrard KP, Barry JA, Muddiman DC. MSiReader: an open-source interface to view and analyze high resolving power MS imaging files on Matlab platform. J Am Soc Mass Spectrom. 2013 May;24(5):718-21. doi: 10.1007/s13361-013-0607-z. Epub 2013 Mar 28.

  PMID: 23536269 BACKGROUND

MeSH Terms

Interventions

Colonoscopy

Intervention Hierarchy (Ancestors)

Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures

Study Officials

• Angela DM Kashuba, PharmD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy

Study Record Dates

• First Submitted: December 17, 2015
• First Posted: December 29, 2015
• Study Start: April 13, 2016
• Primary Completion: August 29, 2017
• Study Completion: August 29, 2017
• Last Updated: January 17, 2018

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)