Based on previous efficacy data on other dual protease inhibitor combinations, this study combining the use of IDV with NFV was undertaken to determine the PK and antiviral activity of the combination that allows for favorable twice daily dosing of IDV. A three part PK study design using varying doses of IDV and NFV was undertaken. For the 21 male study subjects enrolled, 58% were antiretroviral naïve and 42% were NRTI-experienced. The median CD4 count was 259 (range 120-568) and the median viral load was 50,500 copies/mL (range 9,090-316,170). Results from the PK data demonstrated that the AUC, trough, and Cmax levels of IDV 1,200 mg BID when co-administered with NFV 1,250 mg BID was similar to historical controls using IDV 800 mg q8h. IDV, however, had no appreciable effect on NFV levels.
Of the 21 patients enrolled in the PK studies, 8 had discontinued the study; 5 because of increasing viral load, 2 for poor adherence, and one for rash. The authors report virologic and CD4 data on only the 13 who completed the study (on treatment analysis) for which 10 (77%) had VL<400 copies/mL and had an average 334 cell CD4 cell increase at week 68. Of the nine patients using the ultrasensitive VL assay at the end of the study, 8 were <50 copies/mL. The intention-to-treat analysis, though not reported by the authors, is less optimistic. Of the 21 enrolled study subjects, 10 (48%) had a VL<400 copies/mL. None of the patients had a dose-limiting toxicity, however the majority of reported adverse events were gastrointestinal: 6 (29%) had diarrhea, 4 (19%) had bloating/cramps, and 4 (14%) had nausea.