Didanosine dosed once daily is equivalent to twice daily dosing for patients on double or triple combination antiretroviral therapy

Objective: To compare the antiviral activity, effect on CD4 cell count, and tolerability of didanosine (ddI) administered once daily and twice daily i n HIV-1-infected patients receiving ddI with stavudine or zidovudine, with or without a protease inhibitor. The study was designed to demonstrate that once-daily dosing of ddI was not inferior to twice-daily dosing. Design: Randomized, open-label, multicenter, two-ann study. Patients and Methods: 121 HIV-l-infected adults on a stable regimen includi ng ddI (twice daily) during the previous 3 months with a stable viral load <10,000 copies/ml started therapy. Of these, 62 were randomized to switch t o a combination that included ddI once daily and 59 to continue with ddI tw ice daily. The ddI dose was 400 mg/day (250 mg/day if body weight was <60 k g). The primary efficacy analysis compared the time-averaged difference (TA D) between the two treatment regimens in change from baseline log(10) plasm a HIV-I RNA levels over 24 weeks of therapy, with an equivalence margin bet ween the two treatment groups of <0.5 log(10) copies/ml. Results: At week 24, the mean plasma HIV-1 RNA level had increased by 0.31 and 0.17 log(10) copies/ml in the ddI once-daily and ddI twice-daily groups , respectively. The time-averaged difference between the two groups in chan ge from baseline plasma HIV-1 RNA levels over 24 weeks was (0.05 log(10) co pies/ml (95% confidence interval, -0.21 to +0.12 log(10) copies/ml), indica ting that the antiviral activity of ddI once daily is similar to that of dd I twice daily. After 24 weeks of treatment, changes from baseline in CD4 ce ll counts were similar in the two groups. Both regimens were generally well -tolerated. Conclusions: Once-daily and twice-daily ddI are equally effective at reduci ng plasma HIV-1 RNA levels when used in a combination regimen with stavudin e or zidovudine, with or without a protease inhibitor.