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洛匹那韦/利托那韦挽救疗法用于有蛋白酶抑制剂治疗史的HIV-1感染儿童后的病毒学阳性转归:一项前瞻性队列研究

Positive virological outcome after lopinavir/ritonavir salvage therapy in protease inhibitor-experienced HIV-1-infected children: a prospective cohort study.

作者信息

Resino Salvador, Bellón Jose Ma, Ramos José Tomás, Gonzalez-Rivera Milagros, de José Ma Isabel, González Ma Isabel, Gurbindo Dolores, Mellado Ma Jose, Cabrero Esther, Muñoz-Fernández Ma Angeles

机构信息

Laboratory of Immuno-Molecular Biology, Hospital Gregorio Marañón, Madrid, Spain.

出版信息

J Antimicrob Chemother. 2004 Nov;54(5):921-31. doi: 10.1093/jac/dkh431. Epub 2004 Oct 7.

Abstract

BACKGROUND

Lopinavir/ritonavir has demonstrated antiviral activity in the HIV-infected patient.

OBJECTIVE

To analyse virological response to lopinavir/ritonavir therapy in previously protease inhibitor (PI)-experienced HIV-1-infected children.

MATERIALS AND METHODS

Sixty-seven HIV-1-children on lopinavir/ritonavir were studied in a multicentre prospective cohort observational study. The outcome variables were undetectable viral load (uVL; VL < or =400 copies/mL) and virological failure after uVL with a rebound of VL >400 copies/mL. VL and genotype of HIV-1-isolates were measured using standard assays.

RESULTS

83.5% of children had a 1 log10 VL decrease including 65.6% who reached uVL. Children with >2 changes of antiretroviral therapy (ART) or >5 drugs needed a median time of 3-4 months higher than children with < or =2 changes of ART or < or =5 drugs previous to lopinavir/ritonavir, to reach those values, and the relative proportions (RP) were 2.2 (P =0.038) and 1.9 (P=0.050), respectively. Children with CD4+>15% (P=0.122), VL < or =30,000 (P < 0.001) copies/mL, and age >12 years (P=0.096) achieved an earlier control of VL during the follow-up. The children with virological failure or rebound of VL had higher baseline VL and lower CD4+ T-lymphocytes/mm3 and had taken a greater number of drugs previous to lopinavir/ritonavir. HIV-children with a new nucleoside reverse transcriptase inhibitor (NRTI), or protease inhibitor (PI) or PI plus non-nucleoside reverse transcriptase inhibitors (NNRTI) in the current regimen had a better virological response than children without these new drugs. Also, children with <6 protease mutations had an RP of 2.31 of achieving uVL.

CONCLUSIONS

Highly active antiretroviral therapy (HAART) including lopinavir/ritonavir induces beneficial effects in terms of virological outcome responses, and it is an effective option for salvage therapy in PI-experienced HIV-1-infected children.

摘要

背景

洛匹那韦/利托那韦已在HIV感染患者中显示出抗病毒活性。

目的

分析先前接受过蛋白酶抑制剂(PI)治疗的HIV-1感染儿童对洛匹那韦/利托那韦治疗的病毒学反应。

材料与方法

在一项多中心前瞻性队列观察研究中,对67名接受洛匹那韦/利托那韦治疗的HIV-1感染儿童进行了研究。观察指标为病毒载量不可检测(uVL;病毒载量<或=400拷贝/mL)以及uVL后病毒学失败(病毒载量反弹>400拷贝/mL)。使用标准检测方法测量HIV-1分离株的病毒载量和基因型。

结果

83.5%的儿童病毒载量下降了1个log10,其中65.6%的儿童达到了uVL。接受过>2次抗逆转录病毒治疗(ART)或使用过>5种药物的儿童达到这些值所需的中位时间比在接受洛匹那韦/利托那韦治疗前接受过≤2次ART或使用过≤5种药物的儿童长3 - 4个月,相对比例(RP)分别为2.2(P = 0.038)和1.9(P = 0.050)。CD4+>15%(P = 0.122)、病毒载量<或=30,000(P < 0.001)拷贝/mL以及年龄>12岁(P = 0.096)的儿童在随访期间病毒载量得到了更早的控制。病毒学失败或病毒载量反弹的儿童基线病毒载量更高,CD4+ T淋巴细胞/mm3更低,并且在接受洛匹那韦/利托那韦治疗前使用过更多的药物。当前治疗方案中使用新的核苷类逆转录酶抑制剂(NRTI)、蛋白酶抑制剂(PI)或PI加非核苷类逆转录酶抑制剂(NNRTI)的HIV感染儿童比未使用这些新药的儿童病毒学反应更好。此外,蛋白酶突变<6个的儿童实现uVL的RP为2.31。

结论

包括洛匹那韦/利托那韦在内的高效抗逆转录病毒疗法(HAART)在病毒学结局反应方面具有有益效果,对于先前接受过PI治疗的HIV-1感染儿童,它是挽救治疗的有效选择。

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