Pharmacodynamic effects of zidovudine 600 mg once/day versus 300 mg twice/day in therapy-naïve patients infected with human immunodeficiency virus.
OBJECTIVE
To compare the virologic activity of zidovudine monotherapy administered as 600 mg once/day versus 300 mg twice/day.


METHODS
Phase II, randomized (1:1), open-label study.


METHODS
Thirteen medical centers in the United States.


METHODS
Thirty-two antiretroviral-naive patients infected with human immunodeficiency virus (HIV).


METHODS
Patients were administered either zidovudine 600 mg every 24 hours (16 patients) or 300 mg every 12 hours (16 patients) for 13 days.


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.


CONCLUSIONS
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
Ruane
Peter J
PJ
Tower Infectious Diseases Medical Associates, Inc, Los Angeles, California 90049, USA. peter_ruane@towerid.com
Richmond
Gary J
GJ
DeJesus
Edwin
E
Hill-Zabala
Christina E
CE
Danehower
Susan C
SC
Liao
Qiming
Q
Johnson
Judy
J
Shaefer
Mark S
MS
D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D019562:Viral Load; D015215:Zidovudine / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*
D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine