Ritonavir-saquinavir dual protease inhibitor compared to ritonavir alone in human immunodeficiency virus-infected patients

The objective of this study was to evaluate the antiretroviral efficacy and safety of ritonavir (600 mg twice a day [b.i.d.])-saquinavir (400 mg b.i.d .) compared to ritonavir (600 mg b.i.d.) in patients pretreated and receivi ng continued treatment with two nucleoside analogs. The study was placebo c ontrolled, randomized, and double blind. Inclusion criteria included protea se inhibitor naive status and a viral load of > 10,000 copies/ml. The main end point was viral load at week 24. Forty-seven patients were included (25 given ritonavir and 22 given ritonavir-saquinavir) and monitored until wee k 48. At inclusion, 23% had had at least one AIDS-defining event. Previous treatment durations (mean and standard deviation) were 42 +/- 25 and 37 +/- 23 months, viral loads were 4.75 +/- 0.62 and 4.76 +/- 0.50 log(10) copies /ml, and CD4 cell counts were 236 +/- 126 and 234 +/- 125/mm(3) in the rito navir and ritonavir-saquinavir groups, respectively. At week 24, viral load s were 2.81 +/- 1.48 and 2.08 +/- 1.14 log(10) copies/ml (P = 0.04) and CD4 cell counts were 330 +/- 151 and 364 +/- 185/mm(3) (P = 0.49) in the riton avir and ritonavir-saquinavir groups, respectively. Similar results were ob served at week 48. Moreover, at week 48, 40 and 68% (P = 0.05) and 28 and 5 9% (P = 0.03) of patients achieved viral suppression at below 200 and 50 co pies/ml in the ritonavir and ritonavir-saquinavir groups, respectively. At week 24, six patients in the ritonavir group but only one in the ritonavir- saquinavir group had key mutations conferring resistance to protease inhibi tors. Clinical and biological tolerances were similar in both groups. In nu cleoside analog-pretreated patients, ritonavir-saquinavir has higher antire troviral efficacy than and is as well tolerated as ritonavir alone.