Effect of Gender and HIV Infection on Zidovudine and Lamivudine Pharmacokinetics

Study Overview
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Brief Summary
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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.

Official Title
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Sex and Disease Dependent Nucleoside Analog Toxicity

Conditions
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HIV

Intervention / Treatment
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* Drug: zidovudine 300mg and lamivudine 150mg as Combivir


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HIV-negative<br>This group was used to compare intracellular ZDV- and 3TC-triphosphate concentrations to the HIV-infected group and in men versus women. | Drug: zidovudine 300mg and lamivudine 150mg as Combivir<br>* twice daily for 12 days in the HIV-negative group and indefinitely for their care in the HIV-positive group<br>|
| Active Comparator: HIV-infected<br>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. | Drug: zidovudine 300mg and lamivudine 150mg as Combivir<br>* twice daily for 12 days in the HIV-negative group and indefinitely for their care in the HIV-positive group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, antiretroviral therapy, nucleoside analogs, mitochondrial toxicity, clinical pharmacology, cellular pharmacology, pharmacogenetics