ABT-378 is a novel peptidomimetic HIV protease inhibitor, with 10-fold more potency in vitro than ritonavir; ABT-378 is active in vitro against some ritonavir-resistant HIV. Although ABT-378 has poor bioavailability when used alone, its bioavailability is improved when given with ritonavir. ABT-378 is metabolized by CYP3A in vivo, a process which is inhibited by ritonavir with a low Ki. In contrast, ABT-378 is a weak inhibitor of ritonavir metabolism, which may relate to the improved half-life observed for ABT-378 in the presence of ritonavir. In preliminary studies, ABT-378 has been given to more than 100 HIV-negative subjects for greater than or equal to two weeks. Observations in those studies included mild elevations in TSH, and mild elevations of liver enzymes. The primary objective is to compare the safety and antiviral activity of ABT-378/ritonavir plus stavudine and lamivudine versus nelfinavir plus stavudine and lamivudine in antiretroviral-naive HIV-infected subjects. The secondary objective is to determine the duration of antiviral response in antiretroviral-naive HIV-infected subjects treated with ABT-378/ritonavir plus stavudine and lamivudine. Antiretroviral-naive HIV-infected males and females 18 years of age and older who are not acutely ill are eligible to participate in this study. Patients will be evaluated for antiretroviral activity, safety, and tolerance of the treatment regimen. Additionally, body weight, concurrent medications, adverse experiences, HIV- associated conditions, and medical resources used to manage HIV-associated conditions and adverse events will be recorded.
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