Delaugerre C, Rohban R, Simon A, Mouroux M, Tricot C, Agher R, Huraux J M, Katlama C, Calvez V
Department of Virology, Pitié-Salpêtrière Hospital 83, blvd de l'hôpital, 75013 Paris, France.
J Med Virol. 2001 Nov;65(3):445-8.
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.
研究目的是确定在接受依非韦伦、奈韦拉平或先奈韦拉平后依非韦伦治疗方案失败的HIV-1感染患者中的耐药谱及交叉耐药率，并调查齐多夫定以及更广泛的胸苷类似物核苷是否会在奈韦拉平治疗失败的患者中导致特定的基因型模式。对104例病毒学反弹至非核苷类逆转录酶抑制剂（NNRTI）方案的患者进行了一项研究（依非韦伦组n = 39，奈韦拉平组n = 46，先奈韦拉平后依非韦伦组n = 19）。对可检测到的血浆HIV-1 RNA（> 200拷贝/ml）进行基因型耐药检测。在研究的104例患者中，只有2例患者在未选择NNRTI耐药突变的情况下对奈韦拉平方案无反应。所有接受依非韦伦方案治疗失败的患者都携带了对奈韦拉平具有交叉耐药性的突变（K103N、Y188L、G190S）。在接受奈韦拉平方案治疗失败且存在NNRTI突变的患者中，35例（80%）携带了对依非韦伦具有交叉耐药性的突变（K101E、K103N、Y188L），9例（20%）仅携带了对奈韦拉平具有耐药性的突变（V106A和Y181C）。在先接受奈韦拉平后接受依非韦伦治疗失败的患者中，所有NNRTI耐药谱均导致对所有可用NNRTI产生交叉耐药。在接受奈韦拉平治疗的患者中，当方案中使用胸苷核苷类似物（齐多夫定或司他夫定）时，与依非韦伦交叉耐药相关的突变选择在统计学上更为频繁（P = 0.02）。总之，100%接受依非韦伦治疗的患者在治疗后对奈韦拉平和依非韦伦产生交叉耐药，80%接受奈韦拉平治疗的患者在治疗后产生交叉耐药。奈韦拉平与胸苷类似物同时使用会导致优先选择交叉耐药的NNRTI突变。
