Effect of Gender and HIV Infection on Zidovudine and Lamivudine Pharmacokinetics

University of Colorado Denver (CU Denver)

Status and phase: Completed; Phase 4

Conditions: HIV

Treatments: Drug: zidovudine 300mg and lamivudine 150mg as Combivir

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01386970

04-1101

R01AI064029 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Enrollment: 43 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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43 participants in 2 patient groups

HIV-negative

Active Comparator group

Description:

This group was used to compare intracellular ZDV- and 3TC-triphosphate concentrations to the HIV-infected group and in men versus women.

Treatment:

Drug: zidovudine 300mg and lamivudine 150mg as Combivir

HIV-infected

Active Comparator group

Description:

This group was started on ZDV-3TC based therapy. Intracellular ZDV- and 3TC-triphosphate concentrations were compared in men versus women and the HIV-negative group.

Treatment:

Drug: zidovudine 300mg and lamivudine 150mg as Combivir