Protocol Number: 03-CC-0091

Title:

Global Initiative to Characterize Differences in Antiretroviral Pharmacokinetics in HIV-Infected Populations

Number:

03-CC-0091

Summary:

This study will determine whether blood levels of the anti-HIV medicine nevirapine are different in HIV-infected patients in the United States from patients in Uganda. People from all over the world take medications to treat HIV infection. These medicines work well in some people but not in others, and they cause harmful side effects in some people and not in others. These differences may be related to variations in how much of the drug reaches the blood. Differences in drug blood levels among people in various areas of the world may be attributed to differences in diet, state of health, ability to absorb the medicines from the stomach, ability to eliminate the drugs from the body, and the brand of medicine taken. This study will help scientists learn whether differences in blood levels of HIV medicines are important in determining how well the drugs work in different patient populations.

HIV-infected patients 18 years of age and older in the United States and in Kampala, Uganda who have been on an antiretroviral treatment regimen that includes at least 28 consecutive days of nevirapine may be eligible for this study. Candidates will be screened with a medical history, physical examination, and blood tests.

Participants will have a total of approximately about 5 ounces of blood drawn during this 6- to 8-hour study. They will come to the NIH clinic in the morning, and a catheter (plastic tube) will be inserted into an arm vein for collecting blood. (Alternatively, blood can be collected by a needle inserted into an arm vein.) Blood will be withdrawn according to the following schedule:

- About 5 tablespoons will be collected upon arrival at the clinic after an overnight fast. Within 30 minutes of this blood draw, the patient will have breakfast and take his or her morning dose of nevirapine, along with any other medications that need to be taken at that time.

- 1 tablespoon of blood will be drawn 2 hours after the nevirapine dose.

- 1 tablespoon of blood will be drawn 4 hours later (6 hours after the nevirapine dose).

The blood will be analyzed for levels of nevirapine and possibly other HIV medicines. Some of the blood will be stored for later analysis of genes (cytochrome P450 and MDR1) that are involved in eliminating medicines from the body.

Sponsoring Institute:

Warren G. Magnuson Clinical Center (CC)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

1. Documentation in the patient's medical record of HIV -1 infection using double ELISA or a second confirmatory test (e.g., Western Blot) or any one of the following: detectable p24 antigen, quantifiable plasma HIV RNA, or detectable proviral DNA.

2. Males and females greater than or equal to 18 years of age

3. Laboratory values within acceptable limits

AST/SGOT less than or equal to 5 X upper limit of normal (ULN)

Serum creatinine less than or equal to 2 X ULN

Hemoglobin greater than or equal to 9.0 g/dL

4. Receipt of a stable nevirapine-containing antiretroviral regimen for at least 28 days.

5. Informed consent signed and subject declares that they have been adherent to their nevirapine-containing antiretroviral regimen.

EXCLUSION CRITERIA:

1. Presence of life-threatening or unstable renal, hepatic, cardiovascular, hematologic, neurologic, psychiatric, or respiratory disease, as determined by medical records, or any other condition that may interfere with the interpretation of the study results or not be in the best interest of the subject in the opinion of the investigator.

2. Laboratory values outside acceptable limits

AST/SGOT less than or equal to 5 X upper limit of normal (ULN)

Serum creatinine less than or equal to 2 X ULN

Hemoglobin greater than or equal to 9.0 g/dL

3. Positive pregnancy test.

4. Receipt of IL-2 within 3 months of study participation.

5. Drug or alcohol use that may impair safety or adherence.

6. Poor venous access.

7. Documented or reported fever (less than 38.5 degrees C) within 7 days of screening.

8. Active opportunistic infection requiring therapy.

9. Refusal to agree to allow for specimens to be stored for future research.

10. Greater than 4 loose/soft stools per day.

11. Subject is non-adherent with their nevirapine-containing antiretroviral regimen and/or they have not provided informed consent.

Special Instructions: Currently Not Provided

Keywords:

Race

Ethnicity

Pharmacogenetics

Cytochrome P450

Population Pharmacokinetics

Recruitment Keywords:

HIV

Conditions:

HIV Infection

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Danner SA, et al. A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. European-Australian Collaborative Ritonavir Study Group. N Engl J Med. 1995 Dec 7;333(23):1528-33.

Harris M, et al. A pilot study of nevirapine, indinavir, and lamivudine among patients with advanced human immunodeficiency virus disease who have had failure of combination nucleoside therapy. J Infect Dis. 1998 Jun;177(6):1514-20.

Hoetelmans RM, et al. The effect of plasma drug concentrations on HIV-1 clearance rate during quadruple drug therapy. AIDS. 1998 Jul 30;12(11):F111-5.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

Warren Grant Magnuson Clinical Center (CC)
National Institutes of Health (NIH)
Bethesda, Maryland 20892. Last update: 10/20/2004