Resistance profile and cross-resistance of HIV-1 among patients failing a non-nucleoside reverse transcriptase inhibitor-containing regimen

The objectives were to determine the resistance profile and the rate of cro ss-resistance in HIV-1 infected patients failing an efavirenz or a nevirapi ne or a nevirapine then efavirenz containing regimens, and to investigate i f zidovudine and more generally thymidine analog nucleosides lead to a part icular genotypic pattern in nevirapine failing patients. A study was conduc ted in 104 patients with virological rebound to a nonnucleoside reverse tra nscriptase inhibitors (NNRTI) regimen (efavirenz n = 39, nevirapine n = 46 and nevirapine then efavirenz n = 19). Genotypic resistance testing was car ried out of detectable plasma HIV-1 RNA (> 200 copies/ml). Among the 104 pa tients studied, only two patients failed to respond to the nevirapine regim en without selection of a NNRTI resistance mutation. All patients failing a n efavirenz regimen harboured mutations conferring cross-resistance to nevi rapine (K103N, Y188L, G190S). Among patients failing the nevirapine regimen and presenting with NNRTI mutations, 35 (80%) harboured mutations conferri ng cross-resistance to efavirenz (K101E, K103N, Y188L) and 9 (20%) harboure d mutations conferring resistance to nevirapine alone (V106A and Y181C). In patients failing nevirapine then efavirenz therapy, all NNRTI resistance p rofile led to cross-resistance to all available NNRTIs. Among patients rece iving nevirapine, the selection of mutations associated with a cross-resist ance to efavirenz was more frequent statistically when a thymidine nucleosi de analog (zidovudine or stavudine) was used in the regimen (P = 0.02). In conclusion, 100% of patients developed cross-resistance to nevirapine and e favirenz after treatment by efavirenz and 80% after treatment by nevirapine . The use of a thymidine analog concomitantly with nevirapine leads to the preferential selection of cross-resistance NNRTI mutations. (C) 2001 Wiley- Liss, Inc.