Effect of Gender and HIV Infection on Zidovudine and Lamivudine Pharmacokinetics
Condition: HIV
Intervention: zidovudine 300mg and lamivudine 150mg as Combivir
Intervention description: twice daily for 12 days in the HIV-negative group and indefinitely for their care in the HIV-positive group
Intervention MeSH terms: Lamivudine; Zidovudine; Lamivudine, zidovudine drug combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pharmacokinetics; antiretroviral therapy; nucleoside analogs; mitochondrial toxicity; clinical pharmacology; cellular pharmacology; pharmacogenetics

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.
    

Eligibility criteria:

        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.