Cross-resistance among nonnucleoside reverse transcriptase inhibitors limits recycling efavirenz after nevirapine failure
Cross-resistance among nonnucleoside reverse transcriptase inhibitors limits recycling efavirenz after nevirapine failure
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DOI：
10.1089/08892220260190308
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发表时间：
2002-08-10
影响因子：
1.5
通讯作者：
Perno, CF
中科院分区：
文献类型：
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作者：
Antinori, A;Zaccarelli, M;Perno, CF
与HIV对非核苷类逆转录酶抑制剂(NNRTI)的耐药性相关的基因突变的异质性应该可以识别出奈韦拉平(NVP)失败的患者，这些患者可能受益于含有EFV的抢救方案。为了确定含NVP方案失败后再用EFV的可行性，对103例NVP失败患者的基因分型数据进行了分析，以评估EFV耐药突变的发生率。在103名NVP失败的受试者中，有50人(58%)对EFV存在显著的临床耐药。此外，对以前接受过NVP治疗并携带对该药物产生耐药性的单一突变的患者进行了含有EFV的抢救方案的3个月病毒学反应评估。3个月后，接受EFV治疗的受试者中只有2人(17%)的HIV RNA低于500拷贝/毫升，而67名无NNRTI突变的受试者中有35人(52%)(OR，0.18；95%CI，0.03-0.79)。携带单一NNRTI相关突变的患者3个月后HIV-1RNA下降的中位数为-0.63log(10)，而没有任何NNRTI突变的患者中HIV-1RNA下降的中位数为-1.32log(10)。在6名携带单一Y181C/I突变的患者中没有观察到病毒学反应。根据目前的数据，在治疗失败的管理中应避免使用非NNRTI的顺序使用。
Heterogeneity in genotype mutations associated with resistance of HIV to nonnucleoside reverse transcriptase inhibitors (NNRTIs) should allow identification of patients failing nevirapine (NVP) who might benefit from efavirenz (EFV)-containing salvage regimens. To establish the feasibility of recycling EFV after failure of NVP-containing regimens genotypic data on 103 NVP-failed patients were analyzed to evaluate the prevalence of EFV resistance-conferring mutations. A clinically significant resistance to EFV was found in 50 of 103 (58%) of NVP-failed subjects. Furthermore, the 3-month virological response to salvage regimens containing EFV was assessed in patients previously treated with NVP and carrying single mutations conferring resistance to this drug. A proportion of HIV RNA less than 500 copies/ml at 3 months was obtained only in 2 of 12 (17%) of EFV-treated subjects compared with 35 of 67 (52%) of those without NNRTI mutations (OR, 0.18; 95% CI, 0.03-0.79). The median HIV-1 RNA decrease after 3 months was -0.63 log(10) among patients carrying single NNRTI-associated mutations compared with -1.32 log(10) among those without any NNRTI mutations. No virological response was observed in six patients harboring a single Y181C/I mutation. On the basis of the present data, sequential use of NNRTIs should be avoided in the management of treatment failure.