Combination therapy containing ritonavir plus saquinavir has superior short-term antiretroviral efficacy: a randomized trial

Objectives: To compare the efficacy and safety of indinavir 800 mg three ti mes a day, ritonavir 600 mg twice a day, and a combination of ritonavir 400 mg twice a day and saquinavir 400 mg twice a day, when administered with t wo nucleoside analogues. Design: A randomized, open-labelled, controlled trial. Two hundred and eigh ty-four patients started randomized treatment. The primary end-point was th e proportion of patients with HIV RNA of 200 copies/ml or less (Roche Ampli cor) and HIV RNA of 20 copies/ml or less (Roche ultradirect assay) at 6 mon ths. Analysis was performed as intent-to-treat, and missing values were acc ounted for as failures. Results: As of 1 May 1998, 269 patients should have completed 24 weeks of t reatment. The proportion of patients with HIV RNA of 200 copies/ml or less was 71% (indinavir), 67% (ritonavir), and 82% (ritonavir + saquinavir), P = 0.07. In antiretroviral drug-naive patients (n = 119), the corresponding f igures were 63, 57, and 89% (P < 0.01), whereas among drug-experienced pati ents (n = 165) 77, 74, and 77% had HIV RNA of 200 copies/ml or less (P = 0. 90). The same pattern was observed in the ultradirect analysis. All three r egimens were generally safe, but significantly more patients in the ritonav ir group (37%) stopped treatment because of adverse drug reactions compared with the indinavir group (8%) and the ritonavir plus saquinavir group (16% ) (P < 0.001). Conclusions: Treatment with saquinavir plus ritonavir in combination with t wo nucleoside analogues is generally safe, and has superior short-term anti viral efficacy compared with indinavir and ritonavir also combined with two nucleoside analogues in antiretroviral drug-naive patients. Further follow -up is needed to determine the durability of the viral response. (C) 1999 L ippincott Williams & Wilkins.