Systematic review of clinical trials evaluating low doses of stavudine as part of antiretroviral treatment.
Stavudine is a nucleoside analogue used for the treatment of HIV-1 infection, as part of highly active antiretroviral treatment. In developing countries, stavudine is used widely, owing to low cost and inclusion in generic fixed-dose combinations. In developed countries, stavudine is now rarely used, although it is highly effective. This is because newer drugs show lower rates of mitochondrial toxicities, such as lipoatrophy, peripheral neuropathy and lactic acidosis. In the development of stavudine, there was evidence that a dosage of 20-30 mg b.i.d. was effective, but the 40-mg b.i.d. dose gained regulatory approval. This review analyses the clinical trials conducted before and after the regulatory approval of stavudine, and shows that the dose of 30 mg b.i.d. has equivalent antiviral efficacy (given the caveats of meta-analysis), with some evidence of lower rates of peripheral neuropathy and lipoatrophy. With limited resources for HIV-1 treatment in developing countries, and only 25% of eligible patients receiving highly active antiretroviral treatment, low-cost treatment options such as stavudine still need to be pursued, if safety can be improved by dose optimisation.
Hill
Andrew
A
Liverpool University, Liverpool, UK. microhaart@aol.com
Ruxrungtham
Kiat
K
Hanvanich
Mattana
M
Katlama
Christine
C
Wolf
Eva
E
Soriano
Vincent
V
Milinkovic
Ana
A
Gatell
Jose
J
Ribera
Esteban
E
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D004305:Dose-Response Relationship, Drug; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D015201:Meta-Analysis as Topic; D012367:RNA, Viral / Q000187:drug effects; D018119:Stavudine / Q000008:administration & dosage / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018119:Stavudine