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

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Abstract
To compare the antiviral activity of once-daily didanosine (ddI) and twice-daily ddI in combination with stavudine (d4T). Randomized, double-blind, multicenter study. Twenty-one sites in the United States. Eighty-seven antiretroviral-naive, HIV-1-infected adults with baseline plasma HIV RNA counts of ≥10000 copies/ml and CD4 cell counts of ≥100 cells/mm3 started study therapy. Patients received once-daily ddI or twice-daily ddI, each combined with twice-daily d4T. 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. At week 12, median log10 HIV-1 RNA changes were -1.83log10 copies/ml in the once-daily ddI/d4T group and -1.80log10 copies/ml in the twice-daily ddI/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 ddI/d4T minus twice-daily ddI/d4T) in change from baseline plasma HIV RNA levels over the first 12 weeks was 0.14log10 copies/ml (95% CI: -0.11, 0.40). At week 12, subjects averaged an increase in CD4 cell count of over 140 cells/mm3. The TAD between the two treatment groups in change from baseline CD4 cell counts over the first 12 weeks was 2 cells/mm3 (95% CI: -40, 45). Once-daily ddI plus d4T and twice-daily ddI plus d4T were similarly effective in reducing plasma HIV-1 RNA levels and increasing CD4 cell counts over 12-24 weeks of therapy.