Study objective: To compare the virologic activity of zidovudine monotherapy administered as 600 mg once/day versus 300 mg twice/day.
Design: Phase II, randomized (1:1), open-label study.
Setting: Thirteen medical centers in the United States.
Patients: Thirty-two antiretroviral-naive patients infected with human immunodeficiency virus (HIV).
Intervention: Patients were administered either zidovudine 600 mg every 24 hours (16 patients) or 300 mg every 12 hours (16 patients) for 13 days.
Measurements and main results: Plasma HIV-1 RNA concentration was measured daily. Study end points were between-group differences in change from baseline of log10-transformed HIV-1 RNA and in rates of viral load decline measured by the slope of HIV-1 RNA over time. At baseline, mean HIV-1 RNA was similar in the once/day and twice/day groups (4.33 and 4.40 log10 copies/ml, respectively). At day 14, a trend toward lower mean reduction in HIV-1 RNA from baseline was observed in the once/day group (-0.585, 95% confidence interval [CI] -0.728 to -0.442 log10 copies/ml) compared with the twice/day group (-0.849, 95% CI -1.067 to -0.630 log10 copies/ml, p=0.056). Viral load reduction also tended to be slower in the once/day group, as indicated by the smaller slope of viral load decline in the once/day group than in the twice/day group during days 1-14 (-0.045 vs -0.065 logic copies/ml/day, p=0.065). Both zidovudine regimens were similarly well tolerated.
Conclusion: Zidovudine 600 mg once/day has antiviral activity, although less pronounced and more slowly achieved than that seen with zidovudine 300 mg twice/day. No differences were observed between the two treatment groups with respect to safety profile or tolerability