444   Virologic Suppression from Different Thymidine Analogue (TA)-Containing HAART Regimen Sequencing Strategies: VIRA3001.

C. Cohen*¹, N. Graham^2,3, M. St. Clair², A. Hirani², and A. Rinehart².
¹Brookline, MA;²Glaxo Wellcome, Res. Triangle Park, NC; and³Virco Labs.

Background:Recent reports have shown that thymidine analogue (TAM) and multidrug resistance (MDR) mutations result from nonsuppressive d4T-containing regimens in zidovudine (ZDV)-naïve patients (pts).

Methods:VIRA3001, an open-label, prospective, randomized clinical trial, assessed virologic efficacy following therapy (tx) switches guided by phenotypic resistance testing vs. standard of care in pts failing their first PI- containing regimen. TAM and MDR patterns and the effect of these patterns on virologic response were examined in ZDV- or d4T-pretreated pts who switched to d4T- or ZDV-containing HAART regimens at baseline (BL).

Results:In the 99 and 45 pts on HAART regimens containing only ZDV or d4T prior to BL, frequency of any TAM or MDR mutation was 61% and 69%, respectively. A subset of pts who were ZDV-experienced (n = 77, median CD4 = 361 and vRNA = 4.0 log₁₀) or d4T-experienced (n = 26, median CD4 = 281 and vRNA = 4.1 log₁₀) continued or switched to ZDV- or d4T-containing HAART regimens at BL. In this mostly NNRTI-naïve population, 70% of the d4T to ZDV group and 58% of the ZDV to d4T group initiated NNRTI tx at BL. More pts in the ZDV to d4T switch group (n = 57) attained vRNA <400 c/mL at week 16 (60%) than in the d4T to ZDV switch group (n = 10) (20%; p = 0.036 [ITT, M = F]). The ZDV to d4T switch group also had a greater reduction in median log₁₀vRNA levels between BL and week 16 (-1.81) than in the d4T to ZDV switch group (-0.59; p = 0.084).

Conclusions:TAM and MDR mutational patterns in prior d4T- or ZDV-treated pts were very similar in VIRA3001. Virologic response in ZDV-experienced pts who switched to d4T-containing HAART regimens was significantly better than response in d4T-experienced patients who switched to ZDV-containing HAART regimens. These results suggest that thymidine analogue sequencing strategies warrant careful evaluation.