Antiviral activity of enteric-coated didanosine, stavudine, and nelfinavir versus zidovudine plus lamivudine and nelfinavir

Objective: To assess and compare the activity and safety of capsules containing enteric-coated beadlets of didanosine given once daily with stavudine and nelfinavir with that of a standard reference triple drug regimen of zidovudine plus lamivudine and nelfinavir. Design: Multinational, 49-site, prospective, open-label, randomized, two-arm comparison study. Participants: HIV-infected subjects with limited or no previous antiretroviral therapy who had plasma HIV RNA levels of greater than or equal to 2000 copies/mL and CD4 cell counts of greater than or equal to 200/mm(3) (511 were randomized to treatment groups, and 352 completed the study). Interventions: Triple antiretroviral therapy for 48 weeks: didanosine EC (400 mg once daily), stavudine (40 mg twice daily), and nelfinavir (750 mg three times daily) or a twice-daily coformulation of zidovudine (300 mg) plus lamivudine (150 mg) and nelfinavir (750 mg three times daily). Main Outcome Measure: Proportion of subjects with HIV RNA levels of < 400 copies/mL at week 48 based on an "intent-to-treat, missing = treatment failure" analysis. Results: The two treatment groups were similar in the proportion of treatment responders (i.e., HIV RNA level of < 400 copies/mL), with 54% of subjects in the didanosine EC and zidovudine plus lamivudine treatment groups responding at week 48. Results of other analyses supported those of the primary analysis. The two study regimens were associated with similar numbers of adverse events. Conclusions: The antiviral efficacy of a triple combination regimen containing once-daily didanosine EC is similar to that of a reference triple combination regimen.