Corticosteroid administration has been associated with a variety of toxicities, including osteonecrosis and Cushing's Syndrome, in patients with HIV infection. The prevalence of these toxicities has led to speculation that protease inhibitors impair the cytochrome P450 (CYP) 3A4-mediated metabolism of corticosteroids leading to an increase in their systemic exposure and toxicity. Conversely, reduced corticosteroid exposure may be expected when these drugs are coadministrated with CYP3A4 inducers such as the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz. Despite the hypothesized interaction between antiretroviral medications and corticosteroids, drug interactions between agents from these classes have not been formally investigated. The objectives of this study are (1) to determine the impact of the HIV protease inhibitor ritonavir on the pharmacokinetics of prednisolone after administration of oral prednisone to healthy volunteers and (2) to determine the respective influences of chronic dosing with lopinavir-ritonavir (LPV/r) and efavirenz (EFV) on prednisolone pharmacokinetics in HIV+ individuals taking a single dose of prednisone. For the HIV-negative healthy volunteer portion of the study, 10 HIV-negative study subjects will receive a single 20 mg dose of prednisone before, and after 3 and 14 days of ritonavir exposure at 200 mg twice daily. Blood and urine will be collected over 24 hrs after prednisone administration to determine prednisolone pharmacokinetics and renal elimination. Blood will also be collected for determination of MDR1 genotype, which may influence prednisolone disposition. For the portion of the study conducted in HIV-infected volunteers, 3 groups of 10 subjects will be recruited to receive a single 20 mg dose of prednisone followed by serial blood sampling for prednisolone concentrations. The 3 groups will consist of (1) individuals receiving and HIV treatment regimen (for at least 30 days) that includes LPV/r (2) individuals receiving an HIV treatment regimen (for at least 30 days) that includes EFV and (3) individual receiving no antiretroviral treatment or treatment devoid of HIV protease inhibitors or NNRTIs. Prednisolone concentrations will be determined by validated high performance chromatographic methods. Non-compartmental methods will be used to characterize prednisolone pharmacokinetics in all study groups. Pharmacokinetic parameter values will be compared using ANOVA with post-hoc testing. Geometric mean data with 90% confidence intervals will be reported. This study will characterize, for the first time, the influence of antiretroviral medications on the pharmacokinetics of a corticosteroid medication (prednisolone).