Stavudine administered once daily is a nucleoside analogue reverse transcriptase inhibitor. The efficacy (reduction in viral load and increase in CD4+ lymphocyte counts from baseline) of stavudine once daily-containing triple therapy was similar to that of stavudine immediate release (IR)-containing triple therapy in the treatment of antiretroviral-naive patients with HIV infection in two 48-week, randomised, double-blind trials. In the largest trial (n = 783), 80% of patients receiving stavudine 75 or 100mg once daily in combination with lamivudine 150mg twice daily and efavirenz 600mg once daily, and 75% of patients receiving stavudine IR 30 or 40mg twice daily-containing combination therapy, had HIV RNA levels reduced to below the limit of quantification at 48 weeks (<400 copies/ml; intent-to-treat analysis). These findings are supported by those from the smaller trial in 150 patients. Stavudine once daily triple therapy was well tolerated, with the incidence of adverse events being similar to that with stavudine IR. Grades 2-4 treatment related adverse events occurring in > or =3% of patients in either group were dizziness, rash, abnormal dream, headache, insomnia, fatigue and peripheral neurological symptoms. Peripheral neurological symptoms occurred in 3% of patients receiving long-term treatment with stavudine once daily and 6% of patients receiving stavudine IR in a combined analysis.