A randomized trial to investigate the recycling of stavudine and didanosine with and without hydroxyurea in salvage therapy (RESTART).

BACKGROUND Treatment failure during highly active antiretroviral therapy (HAART) is ultimately common and associated with the development of resistance mutations to both the specific drug in question and cross-resistance to other available treatment options. In heavily pre-treated patients, the recycling of antiretroviral agents that have been utilized previously may, however, be associated with antiviral efficacy. We therefore conducted an investigation into the concept of recycling stavudine (d4T, Zerit) and didanosine (ddI, Videx) with and without hydroxyurea, in the management of heavily pre-treated HIV-1 infected individuals requiring salvage therapy (RESTART). METHODS We randomized 21 individuals with treatment failure to receive stavudine and didanosine or stavudine, didanosine and hydroxyurea, for 12 weeks prior to optimizing therapy. Viral load, immunological parameters, genotypic information and the virtual phenotypes were obtained at baseline and at the end of the study. RESULTS Significant decreases in viral loads were observed in both groups during a 12 week study period (P = 0.04), the addition of hydroxyurea conferring no additional benefit. This was not predicted by information from genotypes and virtual phenotypes, and these did not reveal sensitive or specific phenotypic cut-offs for those individuals who responded to recycling. CONCLUSIONS Salvage therapy with didanosine and stavudine can decrease viral loads in heavily pre-treated individuals. Genotypic and virtual phenotype profiles provide little additional information in this setting.