449   Resistance Profile and Cross-Resistance to HIV-1 among 104 Patients Failing a Non-Nucleoside Reverse Transcriptase Inhibitor- Containing Regimen.

C. Delaugerre*, M. Wirden, A. Simon, M. Mouroux, R. Agher, C. Katlama, J. M. Huraux, and V. Calvez.
Pitié-Salpêtrière Hosp., Paris, France.

Background:The objective of this study was to determine the resistance profile and the rate of cross-resistance in patients failing an efavirenz- or a nevirapine- or a nevirapine- and then efavirenz-containing regimen and to investigate whether zidovudine and, more generally, thymidine analog nucleosides lead to a particular genotypic pattern in nevirapine-failing patients.

Methods:A study was conducted in 104 patients harboring a virological failure to a NNRTI regimen (efavirenz n = 39, nevirapine n = 46 and nevirapine then efavirenz n = 19). Genotyping resistance testing were performed on the second point of detectable viral load (>200 copies/ml).

Results:Among the 104 studied patients, only two patients failed a nevirapine regimen without selection of NNRTI resistance mutation. All patients failing an efavirenz regimen harbored mutations conferring cross- resistance to nevirapine (K103N, Y188L, G190S). Among patients failing a nevirapine regimen and presenting NNRTI mutations, 35 (80%) harbored mutations conferring resistance cross-resistance to efavirenz (K101E, K103N, Y188L) and 9 (20%) harbored mutations conferring resistance to nevirapine alone (V106A and Y181C). In patients who failed nevirapine-then-efavirenz therapy, all NNRTI resistance profiles led to cross-resistance to all available NNRTIs. Among patients receiving nevirapine, the selection of mutations associated with a cross- resistance to efavirenz was statistically more frequent when a thymidine nucleoside analog (zidovudine or stavudine) was used in the regimen (p = 0.02).

Conclusions:100% of patients developed cross-resistance to nevirapine and efavirenz after treatment with efavirenz ,and 80% developed it after treatment by nevirapine. When a thymidine analog was included in the nevirapine regimen, the cross-resistance mutations to efavirenz were selected in preference to specific nevirapine resistance mutations.