Concentration-controlled compared with conventional antiretroviral therapy for HIV infection.

Objectives: To demonstrate the feasibility of a concentration-controlled approach to combination antiretroviral therapy, and to compare the virological responses and safety of this strategy versus conventional fixed-dose therapy.

Design: A prospective, randomized, 52 week, open-label trial of concentration-controlled compared with conventional dose zidovudine, lamivudine, and indinavir therapy conduced in a university-based general clinical research center in the United States.

Patients: Forty antiretroviral-naive individuals with plasma HIV-RNA levels > 5000 copies/ml.

Pharmacological basis for concentration-controlled therapy with zidovudine, lamivudine, and indinavir.

Conventional antiretroviral therapy involves administration of standard fixed doses to adults and adolescents. This approach ignores interindividual variability in pharmacokinetics and results in substantial differences in systemic concentrations among patients. Thus, variability in systemic concentrations contributes to variability in response to therapy.

Zidovudine triphosphate and lamivudine triphosphate concentration-response relationships in HIV-infected persons.

Objective: To quantitate intracellular concentrations of zidovudine and lamivudine triphosphate and explore relationships with virologic and immunologic responses to antiretroviral therapy.

Design: Eight antiretroviral-naive, HIV-infected persons with CD4 T cell counts > 100 x 10(6) cells/l, and HIV RNA in plasma > 5000 copies/ml participating in a prospective, randomized, open-label study of standard dose versus concentration-controlled therapy with zidovudine, lamivudine, and indinavir.

Methods: Peripheral blood mononuclear cells and plasma were collected frequently throughout the study for quantitation of intracellular zidovudine triphosphate and lamivudine triphosphate concentrations, and zidovudine and lamivudine concentrations in plasma.

Semen and serum pharmacokinetics of zidovudine and zidovudine-glucuronide in men with HIV-1 infection.

Study Objective: To characterize the concentration-time profiles of zidovudine and zidovudine-glucuronide in semen and serum of men infected with the human immunodeficiency-1 virus (HIV-1).

Design: Open-label observational study.

Setting: University-affiliated teaching hospital and research center.

Pharmacodynamics of human immunodeficiency virus type 1 protease inhibitors.

Many factors are involved in the success or failure of antiretroviral therapy. Recent data suggest that there are significant differences in drug absorption and disposition for the protease inhibitor class of antiretroviral drugs, and relationships between plasma concentrations and their antiviral effect have been described. Consequently, the issue of whether therapeutic drug monitoring should be employed for patients receiving treatment with these drugs has arisen.

Indinavir concentrations and antiviral effect.

Study Objectives: To determine the variability of indinavir pharmacokinetics in patients attending an outpatient clinic, and to explore relationships between indinavir exposure and antiviral effect.

Design: Open, formal pharmacokinetic evaluation.

Setting: University-affiliated clinical research center.

Variability in zidovudine serum concentrations.

This study explored the variability of zidovudine concentrations with computer simulations and measured concentrations. A one-compartment oral absorption model was selected to characterize zidovudine disposition. Mean (+/-standard deviation) values for the pharmacokinetic parameters were taken from the literature.