Virological response in multidrug-experienced HIV-1-infected subjects failing highly active combination regimens after shifting from lamivudine to didanosine

The aim of this study (the RESCUE trial) was to verify the effect of a shif t from a lamivudine-containing to a didanosine-containing regimen on viral replication in HIV-1-infected subjects who had experienced prior treatment failure. Sixteen patients (didanosine-experienced in 14/16 cases) were cons ecutively enrolled: eight patients shifted from lamivudine to didanosine wi thout other changes in their drug regimen. The other eight shifted from lam ivudine to didanosine and changed one or more of their other drugs accordin g to their physician's judgement. At the time of the regimen shift, all the subjects exhibited a high-level phenotypic resistance to both zidovudine a nd lamivudine with changes at codons 70-219 in 100% of cases, at codon 215 in 13 of 16 patients, and the M184V substitution in 13/16 patients. Phenoty pic susceptibility to didanosine was maintained in the majority of cases (1 4/16) despite the high prevalence of changes at codon 184. A statistically significant decrease in viral load (P <0.005) without a significant increas e in CD4 lymphocytes (P=0.514) was observed after 3 and 6 months from the i ntroduction of the didanosine-containing regimen. These findings suggest th e possibility of achieving a viral load response to didanosine-containing r egimens in patients with reverse transcriptase (RT) M184V mutations who wer e previously treated with this drug and its possible use in salvage combina tions.