July 11, 2002
Dr. Ruane and colleagues conducted a pilot study comparing the antiviral efficacy of monotherapy with either BID (300 mg BID) or QD (600 mg) AZT (zidovudine, ZDV). With the increasing interest in once-a-day dosing regimens, limited data regarding the intracellular kinetics of AZT-triphosphate (the active moiety) suggest that the half-life could be up to 11 hours, which would support the use of once-daily dosing of AZT. Thirty-two antiretroviral naive HIV-infected patients were randomized to receive one of the two dosing regimens of AZT for 14 days. The objective was to compare the antiviral effect after 14 days. Concerns about the possibility of promoting resistance were addressed by looking at the resistance pattern at baseline and after 14 days.
Median change of viral level was -0.55 log in the QD and -0.72 log in the BID arms of the study (difference = 0.17 log) while the difference in the mean viral log change was -0.27 log. The study was powered to have an 80 percent chance to detect a difference of 0.5 log RNA between the two groups. Genotypic studies found no evidence of resistance after the 14 days of treatment in either arm in a total of nine study subjects.
It is a challenge to assess the antiviral activity of a single agent in the era of combination therapy. In a case where the drug is a low barrier to resistance (i.e., 3TC or nevirapine), such monotherapy evaluations are not recommended. For drugs with more complex pathways to resistance, short-term studies can dissect out key aspects of antiviral activity. This study was underpowered to truly assess whether QD AZT use can be utilized but does provide some reassurance to go ahead with additional studies. With the ultimate goal of finding a potent regimen that requires just one or two pills once daily, it is worthwhile to evaluate whether AZT has any future role in that direction. Further studies of intracellular levels of AZT-triphosphate and single clone resistance tests would be useful to include in future studies looking at once daily AZT regimens.
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