TBTC Study 23B:Intensive PK of the Nelfinavir Rifabutin Interaction in Patients With HIV-TB

Primary Objective:

To define the impact of nelfinavir (given at 1250mg bid as part of a combination antiretroviral regimen) on peak levels and area under the curve for rifabutin and the rifabutin metabolite, 25-O-desacetyl rifabutin when rifabutin is given at 300 mg bi-weekly as part of tuberculosis chemotherapy.

Secondary Objectives:

To compare the pharmacokinetics of nelfinavir given twice daily at 1250 mg bid with twice-weekly isoniazid and rifabutin to the pharmacokinetics of nelfinavir 1250 mg twice-daily in historical HIV-infected patients not receiving isoniazid and rifabutin.

To evaluate the correlation between pharmacokinetic parameters of rifabutin and 25-O-desacetyl rifabutin and the occurrence of toxicity attributed to rifabutin in patients with HIV-related tuberculosis.

To define detailed pharmacokinetics of isoniazid given at 15mg/kg or 900 mg in patients with HIV-related tuberculosis.

To attempt to derive optimal sampling times for nelfinavir and rifabutin pharmacokinetic studies.