1. Resistance Mutations Before and After Tenofovir Regimen Failure in HIV-1 Infected Patients. £ Background: Except for the K65R mutation, little is known about tenofovir (TDF) impact on NRTI-associated mutations. The aim of this study was to compare the NRTI mutation profiles before and after TDF-regimen failures. Methods: We selected from our database all patients with a genotypic resistance test performed during a TDF-regimen failure between January 2001 and April 2004. The patients were categorized in two groups according to the presence (group I) or absence (group II) of TAMs documented before TDF initiation. We then compared the baseline NRTI-associated mutations with those present at the time of TDF-regimen failure. The proportions of the two groups were compared using chi-squared tests. Odds-ratios were analysed with a regression logistic test. Results : 96 patients met the criteria. The median number of TAMs in group I was 4 before TDF initiation and did not change at failure because disappearances balanced developments (Table 1). However, a trend towards emergence of K219Q/E/N mutations was observed. The K65R mutation, absent in all baseline genotypes, was developed in 19 of the 96 patients (20%), with an incidence significantly higher in group II than in group I (p<10-4). It can emerge even with TAMs, perhaps promoted by treatment interruption just before TDF introduction. The K65R emergence is strongly associated with absence of TAMs at baseline (p<10-4) and, to a lesser extent, with regimen sparing both PIs and NNRTIs (p=0.0005), even after adjustment in a regression logistic test (Table 2). The absence of tymidine analogue in the TDF-regimen was not associated with the K65R selection, however only 9 regimens included AZT or d4T. The changes regarding the other NRTI-associated mutations mostly concern acquisitions of mutations L74V, V75I, Y115F and V118I. Conclusion : TDF-regimen failure is associated with a strong selection of K65R in absence of TAMs at baseline and with regimens only based on TDF/NRTIs. Further studies are needed to evaluate the impact of the new HIV guideline on the K65R selection rate that should decrease.No obvious impact was shown on TAMs or other NRTI mutations, although a trend towards emergence of L74V, V75I, V118I, Y115F and K219Q/E/N mutations was observed. Discussion : In this study, a great proportion (28%) of these 96 patients experiencing failure received treatment only based on NRTIs with TDF. This concords with prior data showing the inefficiency of such combinations even in patients with favourable genotypic test at baseline as expected in group II. In this present study, most of these combinations comprising only NRTIs was initiated before 2004 in patients with undetectable (75% of them) or very low viral loads. Since the new HIV guideline, these practices are over. This shows that a new compound, at the beginning of its availability, has to be used carefully and in tried and tested combination. M. Wirden, AG Marcelin, A.Simon, M.Kirstetter, R.Tubiana, MA. Valantin, L.Paris, M.Bonmarchand, C.Katlama and V.Calvez *. £ J Med Virol. 2005 Jul;76(3):297-301 Corresponding author : marc.wirden@psl.aphp.fr Poster WePe4.1C07 Pitié-Sâlpetriere Hospital, Paris, France