Status
Conditions
Treatments
About
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.
Full description
Study Design
This is an observational study of TFV, FTC, RAL, ATZ, EFV, and MVC localization within GALT (terminal ileum & rectum), vaginal, and cervical tissues in the setting of undetectable plasma HIV. Participants will be selected on the basis of receiving either TFV/FTC/RAL, TFV/FTC/ATZ/r, TFV/FTC/EFV, or TFV/FTC/MVC as part of their ongoing HIV care. After participant education, informed consent, and screening for study eligibility, participants will be evaluated at baseline. All samples will be collected over the course of a 36 hour inpatient visit as described below.
Study Sampling
Pharmacokinetic Analysis All blood, cervical, vaginal, ileal and rectal tissue samples will be analyzed by the Clinical Pharmacology and Analytical Chemistry Laboratory (CPAC) at the UNC School of Pharmacy, which is directed by the principal investigator, Angela Kashuba, PharmD. To visualize ARV localization within a tissue, one biopsy from each tissue site will be analyzed by IR-MALDESI using a previously established workflow for our laboratory.
HIV localization within tissues will be performed using in situ hybridization (ISH) in collaboration with the Haase lab at the University of Minnesota. This group has substantial experience in HIV RNA detection from human tissues, and preliminary studies have confirmed our ability to detect HIV RNA from serial slices of tissues.
Localization within tissue slices will be evaluated by IR-MALDESI. Measurement of the distribution of each ARV within pre-specified anatomical sub-regions across a tissue slice will allow for identification of areas where drug is either concentrating or lacking. ISH and IHC analysis of serial tissue slices will allow us to co-localize ARVs with HIV and HIV target cells. Once these anatomical areas have been visually identified, imaging software will be used to isolate and quantify the signal.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion Criteria:
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):
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.
Not receiving any known CYP3A4 inducers (rifampin, carbamazepine, St. John's wort) or inhibitors (ketoconazole, non-DHP calcium channel blockers, macrolide antibiotics) other than those contained in their HIV regimen for at least 6 months prior to enrollment.
Subject must be willing to abstain from sexual intercourse, douching, and all intravaginal and intrarectal objects and products for at least 72 hours prior to enrollment until study completion.
Subject must be Hepatitis B surface antigen negative as documented on screening labs (or documented in their clinical record).
Subject must not be actively involved in the conception process.
Subject must be able to swallow pills and have no allergies to any component of the study products (i.e. bowel preparation regimen)
Exclusion Criteria
5 participants in 4 patient groups
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal