Resistance profile and cross-resistance of HIV-1 among patients failing a non-nucleoside reverse transcriptase inhibitor-containing regimen
Resistance profile and cross-resistance of HIV-1 among patients failing a non-nucleoside reverse transcriptase inhibitor-containing regimen
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DOI：
10.1002/jmv.2055
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发表时间：
2001-11-01
影响因子：
12.7
通讯作者：
Calvez, V
中科院分区：
文献类型：
--
作者：
Delaugerre, C;Rohban, R;Calvez, V
目的是确定对依非韦伦或奈韦拉平或奈韦拉平然后含依非韦伦治疗方案失败的 HIV-1 感染患者的耐药情况和交叉耐药率，并调查齐多夫定和更普遍的胸苷类似物核苷是否会导致奈韦拉平失败的患者出现特定的基因型模式。对 104 名使用非核苷逆转录酶抑制剂 (NNRTI) 方案出现病毒学反弹的患者进行了一项研究（依非韦伦 n = 39，奈韦拉平 n = 46，奈韦拉平然后依非韦伦 n = 19）。对可检测的血浆 HIV-1 RNA（> 200 拷贝/ml）进行基因型耐药性测试。在所研究的 104 名患者中，只有两名患者在未选择 NNRTI 耐药突变的情况下对奈韦拉平治疗方案没有反应。所有依非韦伦治疗方案失败的患者均携带对奈韦拉平产生交叉耐药性的突变（K103N、Y188L、G190S）。在奈韦拉平治疗失败并出现 NNRTI 突变的患者中，35 例 (80%) 携带对依非韦伦交叉耐药的突变 (K101E、K103N、Y188L)，9 例 (20%) 携带对单独奈韦拉平耐药的突变 (V106A 和 Y181C)。在奈韦拉平和依非韦伦治疗失败的患者中，所有 NNRTI 耐药谱都会导致对所有可用 NNRTI 的交叉耐药。在接受奈韦拉平治疗的患者中，当治疗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，依非韦伦治疗后 100% 的患者对奈韦拉平和依非韦伦产生交叉耐药，奈韦拉平治疗后 80% 的患者出现交叉耐药。胸苷类似物与奈韦拉平联合使用会优先选择交叉耐药性 NNRTI 突变。 (C) 2001 Wiley-Liss, Inc.
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 nonnucleoside 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. (C) 2001 Wiley-Liss, Inc.