WHO spells out how d4T dose reduction should be implemented

Keith Alcorn
Published: 08 May 2007

The World Health Organization (WHO) has published an update to its antiretroviral treatment guidelines for adults in resource-limited settings, explaining how treatment programmes should go about implementing a reduction in dosing of the nucleoside analogue d4T (stavudine).

The WHO Guidelines Development Group was persuaded of the need to recommend a reduced dose after accumulating reports of serious d4T-related toxicities in developing country treatment programmes, and the presentation of a meta-analysis of studies looking at the efficacy and safety of a reduced dose.

Previously, the preferred d4T dosing was weight-based. Dosing for patients weighing more than 60kg was recommended at 40mg twice daily; dosing for patients weighing less than 60kg was recommended at 30mg twice daily.

In a statement issued on Monday, WHO’s HIV/AIDS department said: “A systematic review of nine randomised trials and six observational cohort studies strongly suggests that stavudine-containing regimens maintain clinical and virologic efficacy when stavudine is dosed at 30mg twice daily, and that this reduced dose is associated with lower rates of toxicity, especially peripheral neuropathy, compared to the 40mg twice daily dose.”

“Based on available evidence, the GDG has concluded that the 30mg formulation of stavudine, dosed twice daily, should be used for all adult and adolescent patients, irrespective of body weight. This recommendation, which was previously considered an option, is now established as the preferred approach when d4T is used as part of an ARV therapeutic regimen.”

Programmatic implications

WHO says treatment programmes should implement the following guidelines for managing the dose switch:

  • All new patients with weight over 60kg being prescribed a stavudine-containing regimen should be started on d4T 330mg only. No patients already receiving d4T 30mg should be stepped up to d4T 40mg.
  • All patients receiving d4T 30 mg or 40 mg with evidence of stavudine-related toxicity (even with no signs of treatment failure) should be moved to a non-stavudine-containing regimen, according to current WHO ART guidelines.
  • All patients receiving d4T 40mg without evidence of stavudine toxicity, should be moved to d4T 30mg , as soon as possible, considering the programmatic feasibility.
  • Any new procurement orders of stavudine in either single or fixed dose combinations should only include d4T 30mg.
  • Any procurement orders of d4T 40mg in either single or fixed dose combinations should, to the extent possible, be cancelled and be replaced with d4T 30mg containing products