Zidovudine and lamivudine: results of phase III studies

It has become apparent that the beneficial effects of zidovudine (AZT) and other antivirals will not continue indefinitely. However, synergistic activity of lamivudine (3TC) in combination with AZT, as well as reversal of phenotypic AZT resistance due to the presence of 3TC resistance-inducing mutations, has been documented in vitro. Two trials (NUCB 3001 and NUCB 3002) are therefore investigating the potential of the combination of 3TC with AZT. HIV-1-positive patients with CD4 cell counts of 100-400 cells/mm3 who had not previously received AZT were enrolled into study NUCB 3001 and treated with either AZT (200 mg t.i.d.) or 3TC (300 mg b.i.d.) plus AZT (200 mg t.i.d.) for 24 weeks. Open-label treatment with the combination regimen was offered for an additional 24 weeks. Both treatment groups experienced an initial increase in CD4 cell count. This increase was significantly greater and more sustained in the combination treatment group than in those receiving AZT monotherapy. Participants originally receiving AZT monotherapy, who changed to combination therapy after 24 weeks, experienced a rise in CD4 count. Those who began the study receiving combination therapy maintained their increased CD4 count for the duration of the study. A statistically significant difference in CD4 cell count between the two treatment groups was observed over the entire 48-week treatment period (p