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首页> 外文期刊>The open AIDS journal >Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens
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Treatment-Emergent Mutations and Resistance in HIV-Infected Children Treated with Fosamprenavir-Containing Antiretroviral Regimens

机译：含有福沙那韦的抗逆转录病毒药物治疗的HIV感染儿童的治疗突变和耐药性

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Treatment-emergent mutations and drug resistance were analyzed in virus from HIV-infected children meeting virologic failure (VF) criteria over 48 weeks following treatment with unboosted fosamprenavir or fosamprenavir/ritonavir-containing regimens in studies APV20002 and APV29005. Both antiretroviral therapy (ART)-na?ve and ART-experienced patients were enrolled. Patients met VF criteria by either failing to suppress HIV-RNA to <400 copies/mL through week 24 or after confirmed viral rebound (≥400 copies/mL) anytime through week 48. Viral isolates were analyzed for treatment-emergent mutations or reduced drug susceptibility. Through week 48, 25/109 (23%) of APV29005 and 9/54 (17%) APV20002 study patients met VF. VF was more common in ART-experienced patients (68% and 78%, respectively). Major or minor treatment-emergent mutations were detected at VF in virus from 3 patients receiving unboosted fosamprenavir-containing regimens and in virus from 10 patients receiving fosamprenavir/ritonavir-containing regimens across the two studies. Major protease inhibitor mutations and the reverse transcriptase mutation M184V were detected at VF in virus from 4 and 5 patients, respectively, across both studies. Reduced drug susceptibility to any drug emerged in virus from 9 patients at VF, although reduced fosamprenavir susceptibility emerged in virus from only 4 patients (2 ART-na?ve and 2 ART-experienced). No cross-resistance to the protease inhibitor darunavir was observed.In conclusion, given the high proportion of ART-experienced children (71%) in these two studies, the overall incidence of children meeting VF criteria through 48 weeks was relatively low (21%) and development of fosamprenavir reduced drug susceptibility at VF was uncommon, further supporting the use of fosamprenavir-containing ART regimens in HIV-infected children.
机译：在研究APV20002和APV29005中，对未经HIV感染或接受fosamprenavir / ritonavir治疗的病毒感染符合HIV失败标准（VF）的儿童，在48周内分析了治疗后突变和耐药性。既有未接受过抗逆转录病毒治疗（ART）的患者也有经历过ART的患者。患者符合VF标准，原因是直到第24周都没有将HIV-RNA抑制到<400拷贝/ mL，或者直到第48周任何时候都没有确认病毒的反弹（≥400拷贝/ mL）。分析了病毒分离株的治疗突变或药物减少易感性。到第48周，APV29005的25/109（23％）和APV20002研究的9/54（17％）的患者达到了VF。 VF在有ART经验的患者中更为常见（分别为68％和78％）。在两项研究中，从3例接受未加用氟沙那韦的方案的患者的病毒中，在VF处检测到主要或次要的治疗突变，而在10例接受含氟沙那韦/利托那韦的方案的患者的病毒中检测到了主要或次要的突变。在两项研究中，分别在4和5位患者的病毒中，在VF处检测到主要的蛋白酶抑制剂突变和逆转录酶突变M184V。 VF的9例患者对病毒的药物敏感性降低，尽管只有4例患者的2病毒对fosamprenavir敏感性降低（2例未接受过ART和2例经历过ART）。没有观察到与蛋白酶抑制剂darunavir的交叉耐药性。综上所述，鉴于这两项研究中具有ART经验的儿童比例很高（71％），因此在48周内达到VF标准的儿童总体发生率相对较低（21％ ），在肺部使用fosamprenavir降低药物敏感性的情况并不常见，这进一步支持了含有fosamprenavir的抗逆转录病毒治疗方案在HIV感染儿童中的使用。

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