Virological and immunological responses to once-daily dosing of didanosine in combination with stavudine

Objective: To compare the antiviral activity of once-daily didanosine (ddl) and twice-daily ddl in combination with stavudine (d4T). Design: Randomized, double-blind, multicenter study. Setting: Twenty-one sites in the United States. Patients: Eighty-seven antiretroviral-naive, HIV-l-infected adults with baseline plasma HIV RNA counts of greater than or equal to 10 000 copies/ml and CD4 cell counts of greater than or equal to 100 cells/mm(3) started study therapy. Interventions: Patients received once-daily ddl or twice-daily ddl, each combined with twice-daily d4T. Main outcome measures: Plasma HIV-1 RNA levels, CD4 cell counts, and adverse events were regularly monitored. The primary efficacy analysis used was the time-averaged difference (TAD) between treatment regimens in change from baseline plasma HIV-1 RNA levels over the first 12 weeks of therapy. Results: At week 12, median log(10) HIV-1 RNA changes were -1.83 log(10) copies/ml in the once-daily ddl/d4T group and -1.80 log(10) copies/ml in the twice-daily ddl/d4T group, and 18 out of 44 patients (41%) and 17 out of 43 patients (40%), respectively, had HIV-1 RNA levels below 400 copies/ml. Similar results were seen at week 24. The TAD between the two treatment groups (once-daily ddl/d4T minus twice-daily ddl/d4T) in change from baseline plasma HIV RNA levels over the first 12 weeks was 0.14 log(10) copies/ml (95% CI: -0.11, 0.40). At week 12, subjects averaged an increase in CD4 cell count of over 140 cells/mm(3). The TAD between the two treatment groups in change from baseline CD4 cell counts over the first 12 weeks was 2 cells/mm(3) (95% CI: -40, 45). Conclusion: Once-daily ddl plus d4T and twice-daily ddl plus d4T were similarly effective in reducing plasma HIV-1 RNA levels and increasing CD4 cell counts over 12-24 weeks of therapy. (C) 1999 Lippincott Williams & Wilkins.