In vivo antagonism with zidovudine plus stavudine combination therapy

Human immunodeficiency virus (HIV)-infected subjects receiving zidovudine w ere randomized either to add stavudine (d4T) or didanosine (ddI) to their c urrent regimen or to switch to ddI or d4T monotherapy, After 16 weeks of th erapy, the mean reduction in HIV RNA from baseline was 0.14 log(10) copies/ mL in patients receiving d4T or zidovudine plus d4T. In subjects receiving ddI or ddI plus zidovudine, reductions were 0.39 and 0.56 log(10), respecti vely. CD4 cell counts remained stable or showed modest increases in all arm s except the zidovudine plus d4T arm. Patients receiving zidovudine plus d4 T showed progressive declines in CD4 cell counts with a median of 22 cells/ mm(3) below baseline by 16 weeks. Examination of intracellular levels of d4 T-triphosphate in 6 subjects was consistent with previous in vitro studies demonstrating pharmacologic antagonism between zidovudine and d4T. Analysis of these data suggests that zidovudine and d4T should not be prescribed in combination and that ddI provides greater antiviral activity than d4T in z idovudine-treated patients.