A new extended release formulation of d4T (stavudine), dosed
once daily, is just as potent as twice daily d4T and may result in fewer side
effects, according to results of a 48 week study presented at the Eighth
European Conference on Clinical Aspects of Treatment of HIV Infection.
The study, presented by Dr Julio Montaner of the University
of British Columbia, Vancouver, involved 150 treatment-naïve patients who were
randomized to receive treatment with a triple regimen of efavirenz, 3TC and
either standard d4T or extended release d4T (at a dose of 100mg a day in those
weighing over 60kg, and 75mg a day in those weighing less than 60kg). 3TC was
dosed twice daily in this study.
Median baseline viral load was 49,000 copies in the extended
release arm and 42,600 in the twice daily arm. After 48 weeks, the proportions
with viral load below 50 copies were 50% and 49% respectively by intent to
treat analysis, although the discontinuation rate was twice as high in the
twice daily arm (18% vs 9%). This was driven largely by non-adherence and
adverse events. There were no significant differences in adverse events, but a
trend was apparent towards more cases of peripheral neuropathy in the twice
daily arm (11% vs 1%).
Implications
These data do not show that taking the current d4T formulation on a once daily basis is safe. The once daily, extended release formulation used in this study is different from the capsules dosed twice daily because it is absorbed less well, according to Dr Andrew Clark of BMS Pharma. Once daily dosing of the current formulation may not be safe and may result in a higher rate of toxicity, so patients should not consider changing their dosing pattern of current d4T capsules on the basis of this study.
Bristol Myers Squibb Pharma, manufacturer of d4T, is likely
to pursue a once daily license for the drug in 2002, and will carry out
studies looking at interactions with other drugs. The company will also study
how food affects the absorption of the drug in more detail, in order to define
what sort of meal the extended release formulation should be taken with. It is probable that an expanded access programme that makes the drug available for patients who have adherence difficulties and who would benefit from a once daily regimen will be set up before the drug is licensed.