Randomized, double-blind comparison of two nelfinavir doses plus nucleosides in HIV-infected patients (Agouron study 511)

Objective: To evaluate the safety and antiretroviral activity of nelfinavir mesylate at two doses as part of a combination regimen in HIV-infected, an ti retroviral-naive patients. Design: Phase III, multicenter, double-blind, placebo-controlled trial. Patients and methods: Two-hundred and ninety-seven patients were randomized to one of three treatment groups: nelfinavir 750 mg three times daily (tid ), nelfinavir 500 mg tid, or matching placebo, each in combination with ope n-label zidovudine (ZDV) 200 mg tid and lamivudine (3TC) 150 mg twice daily (bid). Data were analyzed on an intent-to-treat basis. Results: Sixty-seven percent of patients receiving nelfinavir 750 mg tid, a nd 50% receiving nelfinavir 500 mg tid in combination with ZDV/3TC achieved HIV RNA < 400 copies/ml compared to 7% receiving ZDV/3TC plus placebo (P < 0.001); 55% and 30% of patients in the nelfinavir-containing arms achieved HIV RNA < 50 copies/ml at week 24. This compared with 4% in the placebo-co ntaining arm. For patients continuing nelfinavir treatment (750 mg or 500 m g tid as treated) for a further 6 months, the proportions achieving < 400 c opies/ml at week 48 were 75% and 54% (P = 0.001) and < 50 copies/ml 61% and 37%, respectively (P = 0.004). The mean increases from baseline in CD4 cel l counts were also durable in patients receiving the triple combination nel finavir therapy. The range and incidence of adverse events was similar for the two nelfinavir-containing arms, with diarrhea being the most common adv erse event. Conclusions: Nelfinavir plus ZDV/3TC was superior to ZDV/3TC/placebo. In ad dition, the 750 mg tid nelfinavir dose was better than the 500 mg tid dose. Virologic responses were sustained over 12 months. (C) 2001 Lippincott Wil liams & Wilkins.