Effect of Gender and HIV Infection on Zidovudine and Lamivudine Pharmacokinetics

HIV Clinical Trial

Official title:

Sex and Disease Dependent Nucleoside Analog Toxicity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01386970
• Other study ID #: 04-1101
• Secondary ID: R01AI064029
• Status: Completed
• Phase: Phase 4
• Start date: May 2005
• Est. completion date: July 2010

Study information

• Verified date: March 2020
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluated the blood and blood cell concentrations of zidovudine and lamivudine in men versus women and in those with versus without HIV infection. Additionally, markers of side effects were correlated with blood levels of the drugs. The hypothesis was that women and those with HIV would have higher drug levels, as well as markers of side effects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: July 2010
• Est. primary completion date: July 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Documented physician-diagnosed HIV-infection (HIV+ antibody or plasma HIV-RNA+); HIV-negative volunteers must have a negative HIV-ELISA.

• Age 18 to 55 years;

• Either antiretroviral naïve, or no HIV-therapy in the preceding 6 months;

• Planned antiretroviral regimen includes standard doses of ZDV plus 3TC as part of the antiretroviral regimen. Once- or twice-daily 3TC will be allowed.

Exclusion Criteria:

• Any medical condition that in the opinion of the investigators would jeopardize the intent of the study.

• In the opinion of the investigator, any concomitant immunomodulatory medications, chemotherapeutic agents, investigational drugs, and alternative therapies, including, glucocorticoids, recombinant growth factors or cytokines (e.g. Granulocyte-macrophage colony-stimulating factor, Granulocyte colony-stimulating factor, interferon-alpha or gamma, human growth hormone, etc), ribavirin, birth-control pills, and sex hormones that could interfere with the cellular pharmacology of the study medications;

• Concomitant medications that interfere with renal drug clearances including, tenofovir, adefovir, cidofovir, ganciclovir, probenecid, or any similarly problematic medication in the opinion of the investigators;

• Concomitant warfarin or daily aspirin (to prevent excess bleeding from biopsy).

• Pregnancy or a plan to become pregnant, or menopause;

• Any > or = grade II abnormality in hemoglobin, absolute neutrophil count, routine liver function tests, serum creatinine, or other organ function abnormalities.

• Any medical or personal condition that, in the judgment of the investigators, may influence the subject's ability to comply with study conditions, such as active mental illnesses, or plans to leave the geographical area.

• Inability to give informed consent.

• Triple nucleoside analog reverse transcriptase regimens.

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• zidovudine 300mg and lamivudine 150mg as Combivir
twice daily for 12 days in the HIV-negative group and indefinitely for their care in the HIV-positive group

Locations

Country	Name	City	State
United States	University of Colorado Denver and Health Sciences Center	Aurora	Colorado

Sponsors (3)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Institute of Allergy and Infectious Diseases (NIAID), University of Hawaii

Country where clinical trial is conducted

United States, 

References & Publications (6)

Anderson PL, Rower JE. Zidovudine and Lamivudine for HIV Infection. Clin Med Rev Ther. 2010;2:a2004. — View Citation

Anderson PL, Zheng JH, King T, Bushman LR, Predhomme J, Meditz A, Gerber J, Fletcher CV. Concentrations of zidovudine- and lamivudine-triphosphate according to cell type in HIV-seronegative adults. AIDS. 2007 Sep 12;21(14):1849-54. — View Citation

Anderson PL. Recent developments in the clinical pharmacology of anti-HIV nucleoside analogs. Curr Opin HIV AIDS. 2008 May;3(3):258-65. doi: 10.1097/COH.0b013e3282f85dc1. — View Citation

Ghodke Y, Anderson PL, Sangkuhl K, Lamba J, Altman RB, Klein TE. PharmGKB summary: zidovudine pathway. Pharmacogenet Genomics. 2012 Dec;22(12):891-4. doi: 10.1097/FPC.0b013e32835879a8. — View Citation

Rower JE, Klein B, Bushman LR, Anderson PL. Validation of a sensitive LC/MS/MS method for the determination of zidovudine and lamivudine in human plasma. Biomed Chromatogr. 2012 Jan;26(1):12-20. doi: 10.1002/bmc.1617. Epub 2011 Apr 4. — View Citation

Rower JE, Meditz A, Gardner EM, Lichtenstein K, Predhomme J, Bushman LR, Klein B, Zheng JH, Mawhinney S, Anderson PL. Effect of HIV-1 infection and sex on the cellular pharmacology of the antiretroviral drugs zidovudine and lamivudine. Antimicrob Agents C — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ZDV-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject	To compare ZDV- triphosphate concentrations in HIV-negative versus HIV-infected subjects.	Day 12 of dosing
Primary	3TC-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject	To compare 3TC- triphosphate concentrations in HIV-negative versus HIV-infected subjects.	Day 12 of dosing