Improving patient adherence with antiretroviral therapy: evaluation of once-daily administration of didanosine

One important goal of antiretroviral therapy should be simplification of treatment regimens whenever possible, in order to enhance adherence and potentially improve treatment outcome. While the nucleoside didanosine (ddI) has generally been dosed twice daily in clinical trials, the long intracellular half-life (>12 h) of its active metabolite, dideoxyadenosine triphosphate, should permit once-daily administration of this antiretroviral agent. The STADI trial evaluated this possibility by administering once-daily ddI and twice-daily stavudine (d4T) to antiretroviral-naive patients with human immunodeficiency virus type 1 (HIV-1) infection. This combination was well tolerated and at the end of 24 weeks of therapy, viral load was reduced by -1.48 log copies/ml and HIV-1 RNA was below the lower limit of quantification (500 copies/ml) in 62% of patients. Twenty-four weeks of treatment with d4T plus once-daily ddI increased average CD4 cell counts by 139/ml. The effectiveness of once-daily administration of ddI will be evaluated further in a new multinational clinical trial, AI454-148, in which it will be combined with d4T and the protease inhibitor, nelfinavir. The primary endpoint of this trial will be durable reduction of plasma HIV-1 RNA below 400 copies/ml. Such a change in the treatment regimen for this nucleoside has the potential to improve patient adherence and, thus, treatment outcome.