A Pilot Study to Characterize the Pharmacokinetics of Raltegravir in the Cervicovaginal Fluids of HIV-infected Women

HIV Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00774683
• Other study ID #: CID 0706 Sub-study A
• Status: Completed
• Phase: N/A
• First received: October 15, 2008
• Last updated: October 21, 2011
• Start date: August 2008
• Est. completion date: September 2009

Study information

• Verified date: October 2011
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 49 Years

Eligibility

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 ß-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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• AIDS
• HIV

Intervention

Drug:
• Raltegravir (Isentress®)
400 mg p.o. BID x 7 days

Locations

Country	Name	City	State
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Kristine Patterson, MD	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

References & Publications (7)

Blankson JN, Persaud D, Siliciano RF. The challenge of viral reservoirs in HIV-1 infection. Annu Rev Med. 2002;53:557-93. Review. — View Citation

Cohen MS. Preventing sexual transmission of HIV. Clin Infect Dis. 2007 Dec 15;45 Suppl 4:S287-92. doi: 10.1086/522552. — View Citation

Lallemant M, Jourdain G, Le Coeur S, Mary JY, Ngo-Giang-Huong N, Koetsawang S, Kanshana S, McIntosh K, Thaineua V; Perinatal HIV Prevention Trial (Thailand) Investigators. Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand. N Engl J Med. 2004 Jul 15;351(3):217-28. Epub 2004 Jul 9. — View 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. Erratum in: J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):492. — View Citation

Musicco M, Lazzarin A, Nicolosi A, Gasparini M, Costigliola P, Arici C, Saracco A. Antiretroviral treatment of men infected with human immunodeficiency virus type 1 reduces the incidence of heterosexual transmission. Italian Study Group on HIV Heterosexual Transmission. Arch Intern Med. 1994 Sep 12;154(17):1971-6. — View Citation

Otten RA, Smith DK, Adams DR, Pullium JK, Jackson E, Kim CN, Jaffe H, Janssen R, Butera S, Folks TM. Efficacy of postexposure prophylaxis after intravaginal exposure of pig-tailed macaques to a human-derived retrovirus (human immunodeficiency virus type 2). J Virol. 2000 Oct;74(20):9771-5. — View Citation

Pierson T, Hoffman TL, Blankson J, Finzi D, Chadwick K, Margolick JB, Buck C, Siliciano JD, Doms RW, Siliciano RF. Characterization of chemokine receptor utilization of viruses in the latent reservoir for human immunodeficiency virus type 1. J Virol. 2000 Sep;74(17):7824-33. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		Single Time Point Measurement at 4 Weeks after ART Initiation	No