Levels of Raltegravir in the Female Genital Tissue
| Status: | Recruiting |
|---|---|
| Conditions: | HIV / AIDS |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - 50 |
| Updated: | 11/30/2013 |
| Start Date: | October 2011 |
| Contact: | Evangelyn Nkwopara |
| Email: | evangelc@u.washington.edu |
| Phone: | 206-221-2792 |
Modeling Intracellular and Extracellular Raltegravir (RAL) Pharmacokinetics in the Female Genital Tract and Blood After a Twice Daily 400mg Dose Over the Course of a Menstrual Cycle
This study is an investigation of the pharmacokinetics of raltegravir in the tissue of the
female genital tract to determine if twice-daily dosing of 400mg achieves adequate drug
levels to prevent viral integration of HIV-1. The study will also assess whether drug levels
change in the tissue across the different phases of the menstrual cycle.
- Hypothesis #1: Twice daily dosing with raltegravir 400mg will result in intracellular
concentrations that should be sufficient to suppress HIV-1 replication throughout the
menstrual cycle.
- Hypothesis #2: Intracellular genital raltegravir peaks will be lower and troughs higher
compared to extracellular concentrations in the plasma and PMBCs (peripheral blood
mononuclear cells).
- Hypothesis #3: Intracellular raltegravir concentrations will be slightly lower during
the luteal phase of the menstrual cycle due to cellular pumps such as p-glycoprotein,
which are present in higher numbers during periods of high progesterone.
HIV-1 is shed in genital secretions which increase the risk of transmission between sexual
partners and from mother to infant. Antiretroviral medication taken prior to exposure to
HIV-1 can prevent viral transmission from a mother to her infant. Raltegravir (RAL), by
blocking integration of viral cDNA into the host's genome, makes an excellent candidate for
preventing HIV-1 infection. RAL is licensed for treatment with twice-daily dosing based on
plasma trough concentrations; however, intracellular concentrations of RAL which are
relevant to blocking infection of cells have not been previously studied. P-glycoprotein
pumps, which are involved in regulating drug absorption and metabolism, can influence
intracellular drug concentrations. P-glycoprotein concentrations appear to vary with
menstrual cycle suggesting it may affect intracellular drug concentration of RAL in women.
Women will be enrolled in the study and followed during the course of a menstrual cycle
while taking a dose of 400mg PO twice daily. An initial screening visit will be performed
prior to enrollment and participation in the study. Review of medical history as well as
blood and urine collection will occur during the screening visit. Once enrolled,
participants will have blood and genital tract samples collected once a week for four weeks
to assess intracellular concentrations of RAL in the blood and genital tract tissue.
Inclusion Criteria
Volunteers must be:
- Over 18 years of age.
- Willing to abstain from sexual intercourse during course of study.
- Able to commit to follow-up visit schedule.
- Willing to abstain from use of vaginal medications or creams 48 hours prior to
follow-up visits.
- Willing and able to provide informed consent.
Exclusion Criteria
Volunteers will not be eligible for the study if they:
- Are over 50 years of age.
- Are pregnant, attempting to become pregnant, or breast-feeding.
- Have irregular menstrual bleeding.
- Are using a hormonal form of birth control.
- Have abnormal liver/kidney function test results at screening visit.
- Have HIV-positive test result at screening visit.
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