An open label, pilot study of the efficacy and tolerability of once daily ddI versus twice daily ddI

Rationale: ddI is dosed on a twice dairy (B.I.D.) schedule but it has limited tolerability and compliance. Intracellular levels of the active component of ddI suggest that this agent may be effective with once daily dosing (Q.d). Q.d dosing may also improve tolerability and compliance to ddI. We performed a randomized trial to compare the relative ability of Q.d and B.I.D. ddI to suppress viral load. Methods: HIV infected patients with a CD4 count < 500 cells/mm3 were randomized to receive once daily ddI (400/day) or twice dairy ddI (200 mg B.I.D.). CD4 counts and viral load were measured at baseline and every 8 weeks for a total of 26 weeks. The study was stopped before enrollment was completed because the standard of care changed from monotherapy to dual and triple combination therapy. Sufficient data was available to compare viral load (VL) and CD4 count change at 8 weeks. Results: 16 subjects were enrolled into the study. There were no differences in Q.d group and the B.I.D. group in the baseline characteristics except for CD4 count (242 cells/mm3 vs. 58 cells/mim3). Baseline viral load was similar in the Q.d and B.I.D. group (169,384 copies/ml vs. 136,555 copies/ml). Viral load changes at week 8 was similar in Q.d and B.I.D. group (-0.42 logs vs. -0.34, P=N.S.). 2/5 evaluable subjects in the Q.d group had >1.0 log decrease in VL compared to 0/7 evaluable subjects in the B.I.D. group. One B.I.D. subject developed pancreatitis while 3 Q.d subjects stopped drug for intolerance. 5/8 subjects in each group were compliant with their regimens. Conclusions: Q.d ddI suppressed VL as well as B.I.D. ddI. Tolerability and compliance profiles were similar in each group. Further study of Q.d ddI dosing should be performed using multi-drug anti-retroviral regimens.