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

✍ Scribed by C. Delaugerre; R. Rohban; A. Simon; M. Mouroux; C. Tricot; R. Agher; J.M. Huraux; C. Katlama; V. Calvez

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 80 KB
• Volume: 65
• Category: Article
• ISSN: 0146-6615
• DOI: 10.1002/jmv.2055

✦ Synopsis

Abstract

The objectives were to determine the resistance profile and the rate of cross‐resistance in HIV‐1 infected patients failing an efavirenz or a nevirapine or a nevirapine then efavirenz containing regimens, and to investigate if zidovudine and more generally thymidine analog nucleosides lead to a particular genotypic pattern in nevirapine failing patients. A study was conducted in 104 patients with virological rebound to a non‐nucleoside reverse transcriptase inhibitors (NNRTI) regimen (efavirenz n = 39, nevirapine n = 46 and nevirapine then efavirenz n = 19). Genotypic resistance testing was carried out of detectable plasma HIV‐1 RNA (> 200 copies/ml). Among the 104 patients studied, only two patients failed to respond to the nevirapine regimen without selection of a NNRTI resistance mutation. All patients failing an efavirenz regimen harboured mutations conferring cross‐resistance to nevirapine (K103N, Y188L, G190S). Among patients failing the nevirapine regimen and presenting with NNRTI mutations, 35 (80%) harboured mutations conferring cross‐resistance to efavirenz (K101E, K103N, Y188L) and 9 (20%) harboured mutations conferring resistance to nevirapine alone (V106A and Y181C). In patients failing nevirapine then efavirenz therapy, all NNRTI resistance profile led to cross‐resistance to all available NNRTIs. Among patients receiving nevirapine, the selection of mutations associated with a cross‐resistance to efavirenz was more frequent statistically when a thymidine nucleoside analog (zidovudine or stavudine) was used in the regimen (P = 0.02). In conclusion, 100% of patients developed cross‐resistance to nevirapine and efavirenz 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. J. Med. Virol. 65:445–448, 2001. © 2001 Wiley‐Liss, Inc.