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

NCT00774683 | Completed

• 1 other identifier: CID 0706 Sub-study A
• Study Type: observational
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV; AIDS

Keywords

Pilot; Pharmacokinetics; Raltegravir; Cervicovaginal; HIV; Women

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Sub-study Group A

Six HIV-positive African American women from the main study, CID 0706

Drug: Raltegravir (Isentress®)

Interventions

Raltegravir (Isentress®) DRUG

400 mg p.o. BID x 7 days

Also known as: ISENTRESS, MK-0518

Sub-study Group A

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

UNC ID Clinic, Durham County Health Department, Wake County Health Department

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Kristine Patterson, MD: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Related Publications (8)

• 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.

  PMID: 8074601 BACKGROUND

• 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. doi: 10.1128/jvi.74.20.9771-9775.2000.

  PMID: 11000253 BACKGROUND

• 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. doi: 10.1056/NEJMoa033500. Epub 2004 Jul 9.

  PMID: 15247338 BACKGROUND

• Blankson JN, Persaud D, Siliciano RF. The challenge of viral reservoirs in HIV-1 infection. Annu Rev Med. 2002;53:557-93. doi: 10.1146/annurev.med.53.082901.104024.

  PMID: 11818490 BACKGROUND

• 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. doi: 10.1128/jvi.74.17.7824-7833.2000.

  PMID: 10933689 BACKGROUND

• 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.

  PMID: 17133211 BACKGROUND

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

  PMID: 18190301 BACKGROUND

• Isentress (Raltegravir) Prescribing Guide. Merck & Co., Inc. October 2007

  BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

blood specimens and cervicovaginal fluids

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Raltegravir Potassium

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Kristine B Patterson, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

• Angela DM Kashuba, PharmD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: October 15, 2008
• First Posted: October 17, 2008
• Study Start: August 1, 2008
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: October 25, 2011

Record last verified: 2011-10

Locations

US (1)