318   Comparison of HIV RNA Suppression Produced by Triple Regimens Containing either Didanosine Enteric-Coated or Didanosine Tablet Formulations Each Administered Once Daily.

S. Schrader*¹, S. Sharma², D. Seekins³, R. McGovern⁴, E. Connaughton⁴, E. Hoffman⁴, and C. McLaren⁴.
¹HCRN, Houston, TX;²Comprehensive Care, Fort Lauderdale, FL;³St. Joseph's Comprehensive Res., Tampa, FL; and⁴Bristol-Myers Squibb Pharmaceutical Res. Inst., Wallingford, CT.

Background:Buffered formulations of VIDEX (ddI) have been associated with GI side effects. A new, encapsulated, buffer-free formulation of enteric-coated beadlets (ddI EC) was developed to remove several drug interactions and to improve tolerability. This study compared the antiviral activity and safety of ddI EC with ddI tablet, both in combination with d4T and nelfinavir (NFV), in treatment-naive subjects (HIV RNA>5,000 c/mL (Amplicor) and CD4>100 mm³).

Methods:138 subjects (median baseline RNA levels 4.71, 4.63 log₁₀c/mL, CD4 counts 382, 363 cells/mm³in the EC and tablet arms, respectively) were randomized in this open label, 2-arm study to either ddI EC QD/d4T/ NFV (EC regimen) or to ddI tablet QD/d4T/NFV (tablet regimen). The primary objective was to demonstrate similarity (<0.5 log₁₀difference) in antiviral activity by the time averaged difference (TAD) in change from baseline HIV RNA over 48 weeks.

Results:Median HIV RNA levels over 48 weeks showed similar profiles for both regimens, with median values <400 c/mL by week 8. Changes in RNA levels from baseline were similar and sustained through 48 weeks, with a slightly larger decrease in EC recipients (-2.62 and -2.35 log₁₀c/mL for EC and tablet, respectively). The greater effect of the EC regimen over 48 weeks was shown in the TAD analysis (TAD -0.19, 95% CI [-0.43, 0.06]). Safety analyses showed that significantly more subjects discontinued for adverse events from the tablet regimen (17%), suggesting better tolerability of the EC regimen (6%; p = 0.05). The results of the TAD analysis showed little difference in the CD4 cell response between the two regimens (TAD -13.12, 95% CI [-43.02, 16.79]).

Conclusions:The results demonstrate the antiviral efficacy of the ddI EC formulation with a slightly better longitudinal virologic response over time compared with ddI tablets. The convenience of the ddI EC capsules to patients and the improved safety profile resulting from absence of drug interactions may enhance compliance with therapeutic regimens.