319   Comparison of a Triple Combination Regimen Containing an Enteric-Coated Formulation of Didanosine Administered Once Daily Versus a Regimen of Combivir Plus Nelfinavir.

J. Gathe*¹, R. Badaro*², A. Grimwood³, L. Abrams⁴, K. Klesczewski⁴, and C. McLaren⁴.
¹Houston, TX;²Salvador, Brazil;³Cape Town, South Africa; and⁴Bristol-Myers Squibb, Wallingford, CT.

Background:Buffered formulations of Videx (ddI) have been associated with gastrointestinal side effects and have interactions with some drugs. This trial assessed antiviral activity and safety of encapsulated buffer-free, enteric-coated VIDEX (ddI EC).

Methods: AI454-152 is an open-label, randomized, 2-arm multinational study. Treatment-naive subjects with plasma HIV RNA >2000 c/mL and CD4 counts >200 cells/mm³were randomized (1:1) to ddI EC 400 mg QD/ d4T/NFV (EC regimen) or Combivir/NFV (Combivir regimen). Primary efficacy analysis compared the proportion of randomized subjects with HIV RNA <400 c/mL at week 48 (drop-outs = failure). Secondary analyses included longitudinal changes in HIV RNA and CD4 cell counts (TAD) and a composite analysis of treatment failure.

Results:Data from 333 of 511 randomized subjects who had completed 48 weeks were analyzed for efficacy, and safety was evaluated in all treated subjects. In the primary efficacy analysis, similar proportions in both regimens had HIV RNA levels <400 c/mL at week 48 (EC 57%, Combivir 55%) (difference 2.4% favoring EC, 95% CI [-8.3%, 13.0%]). Supporting results were seen for HIV RNA <50 c/mL (difference 0.2%, 95% CI [- 10.1%, 10.5%]) and in a failure analysis (difference -3.8%, 95% CI [-14.5%, 6.9%]). Similar median decreases in HIV RNA levels were observed in both regimens at week 48 (EC 2.7, Combivir 2.6 log₁₀c/mL). Median CD4 counts increased in both regimens (EC 110, Combivir 147 cells/mm³). Adverse events included diarrhea (54%, 56%), infection (43%, 34%), nausea (21%, 35%), vomiting (13%, 18%), headache (20%, 16%), and asthenia (15%, 20%) in EC and Combivir regimens, respectively. Peripheral neurological symptoms (grade I-II) were seen in 63 subjects (EC 17%, Combivir 8%). Discontinuations for adverse events were similar in number, occurring early in Combivir and later in EC.

Conclusions:VIDEX EC given QD as a part of a triple regimen demonstrates antiviral activity similar to that of a reference triple regimen in treatment-naive, HIV-infected subjects. This well-tolerated regimen may improve patient compliance and long-term outcome.