450   Presence of Thymidine- Associated Mutations and Response to d4T, Abacavir and ddI in the Control Arm of the Narval ANRS 088 Trial.

D. Costagliola¹, D. Descamps², V. Calvez², B. Masquelier³, A. Ruffault⁴, F. Telles², J. L. Meynard², and F. Brun-Vezinet².
¹INSERM SC4;²AP-HP, Paris,³CHU, Bordeaux, and⁴CHU, Rennes, France.

Background:Thymidine-associated mutations (TAMs) have been associated with d4T and Abacavir resistance. We aimed at studying the role of TAMs in the virological response observed in the control arm of Narval depending on the NRTI prescribed.

Methods:Genotypic resistance studies were performed on viral plasma RNA using the Visible Genetics TrueGene kit. The association of at least 3 TAMs, including T215Y/F (among M41L, D67N, K70R, L210W, T215Y/F, K219Q/E), with mean decrease in plasma HIV RNA (DVL) at week 12 was studied in patients of the control arm receiving d4T (n = 52,DVL = -1.05 log₁₀copies/ml), Abacavir (n = 74,DVL = -1.27), or ddI (n = 49,DVL = -0.85), as a component of the HAART treatment at baseline. As most patients receiving ddI in the control arm were also receiving either d4T or Abacavir, we also studied patients receiving ddI and 3TC in any arm (n = 36,DVL = -0.96) and patients receiving 3TC in the control arm (n = 46,DVL = -1.03) to study whether the results in ddI-receiving patients could be explained by the type of other NRTIs. An analysis restricted to the 34 patients receiving Abacavir as the only NRTI was also conducted. Mann-Whitney test was used to compare the response according to the presence TAMs, and multiple linear regression was used to account for baseline covariates.

Results:

Results remained the same after adjusting for baseline viral load and number of drugs previously received.

Conclusion:In NRTI-exposed patients, presence of at least 3 TAMs including T215Y/F impaired the virological response to d4T and ddI, even when co-prescribed with NNRTI and/or PI. The response to Abacavir prescribed

as the only NRTI does not appear to be influenced by TAMs. These results may change the therapeutic strategy in the sequential use of NRTI and in the switches of treatment.