Clinical trial NCT00774683: A Pilot Study to Characterize the Pharmacokinetics of Raltegravir in the Cervicovaginal Fluids of HIV-infected Women
Official title: A Phase IV, Open-Label, Single-Sequence Pilot Study to Characterize the Pharmacokinetics of a 400mg Oral Dose of Raltegravir in the Cervicovaginal Fluids of HIV-Infected Women
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV
AIDS
Keywords: Pilot
Pharmacokinetics
Raltegravir
Cervicovaginal
HIV
Women
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2008-10-17
Enrollment: 1
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: UNC ID Clinic, Durham County Health Department, Wake County Health Department

Brief summary: The purpose of this research sub-study is to learn about the levels of an antiretroviral (ARV) medication called Raltegravir, and response to HIV virus in the genital tract of HIV-positive women.

We would like to see how this study medication is tolerated, and how the body processes the study medication in women who are HIV-positive. More specifically, we are interested in how Isentress® might penetrate into the female cervicovaginal secretions thereby potentially reducing the amount of HIV in those secretions. A reduction in the amount of HIV in genital secretions may prevent female subjects from transmitting HIV to their sexual partners. This information will help the research team know how a medication such as Isentress® might be used to prevent the sexual transmission of HIV.

Detailed description: Purpose: This study aims to characterize the pharmacokinetics of raltegravir in cervicovaginal fluids of HIV-infected women, and compare this to the blood plasma pharmacokinetics being obtained in the main study, CID 0706.

Participants: Six HIV-positive women from the CID 0706 study Procedures: During the pharmacokinetic visit to obtain blood plasma in the CID 0706 study, women will be asked to self-collect cervicovaginal samples using a vaginal aspirator at the following timepoints: pre-dose and 1, 2, 4, 6, 8, and 12 hours after raltegravir 400mg dose administration.

Eligibility criteria: Inclusion Criteria:

* HIV-1 infection documented by HIV serology or detectable viral load
* Self-described as African-American
* Less than 7 days cumulative of prior HIV therapy
* Plasma HIV RNA PCR equal to or greater than 1000 copies/mL within 90 days prior to study entry
* Able to provide informed consent
* In the opinion of the investigator, able to comply with study medication and procedures
* ALT (SGPT) \< or equal to 3.0 x ULN within 45 days prior to study entry
* GRF \> 60 as calculated by MDRD within 45 days prior to study entry
* All women of reproductive potential (who have not reached menopause or undergone hysterectomy, bilateral oophorectomy, or tubal ligation) must have a negative serum or urine β-HCG pregnancy test performed within 48 hours before entry.

All study volunteers must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) and, if participating in sexual activity that could lead to pregnancy, the female study volunteer/male partner must use at least one reliable method of contraception (e.g., condoms, with or without a spermicidal agent; a diaphragm or cervical cap with spermicide; an IUD; or hormonal-based contraception), simultaneously while receiving the protocol-specified medication(s) and for 6 weeks after stopping the medication(s).

Exclusion Criteria:

* Pregnancy
* Breastfeeding
* Prior receipt of Raltegravir
* Any condition which in the opinion of the investigator is likely to interfere with follow-up or ability to take the study medication appropriately
* A positive test for bacterial vaginosis, syphilis, gonorrhea, Chlamydia, HSV-2 (active lesions), or trichomonas at entry or week 2 of the main study, CID 0706

Primary outcomes:
measure: To characterize the pharmacokinetics of raltegravir in cervicovaginal fluids of HIV-infected women, and compare this to the blood plasma pharmacokinetics being obtained in the main study, CID 0706.
timeFrame: Single Time Point Measurement at 4 Weeks after ART Initiation
Secondary outcomes:
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Kristine B Patterson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of North Carolina, Chapel Hill
name: Angela DM Kashuba, PharmD
role: PRINCIPAL_INVESTIGATOR
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citation: Markowitz M, Morales-Ramirez JO, Nguyen BY, Kovacs CM, Steigbigel RT, Cooper DA, Liporace R, Schwartz R, Isaacs R, Gilde LR, Wenning L, Zhao J, Teppler H. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2006 Dec 15;43(5):509-15. doi: 10.1097/QAI.0b013e31802b4956.
citation: Cohen MS. Preventing sexual transmission of HIV. Clin Infect Dis. 2007 Dec 15;45 Suppl 4:S287-92. doi: 10.1086/522552.
citation: Isentress (Raltegravir) Prescribing Guide. Merck & Co., Inc. October 2007