Long-term outcomes for HIV-infected infants less than 6 months of age at initiation of lopinavir/ritonavir combination antiretroviral therapy
Long-term outcomes for HIV-infected infants less than 6 months of age at initiation of lopinavir/ritonavir combination antiretroviral therapy
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DOI：
10.1097/qad.0b013e32834403f6
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发表时间：
2011-03-13
期刊：
影响因子：
3.8
通讯作者：
Capparelli, Edmund V.
中科院分区：
文献类型：
--
作者：
Chadwick, Ellen G.;Yogev, Ram;Capparelli, Edmund V.
目的：研究洛匹那韦/利托那韦(LPV/r)在2周~6个月婴儿开始联合抗逆转录病毒治疗(CART)时的纵向药代动力学、安全性和有效性。方法：以LPV/r为基础的CART，剂量为300/75 mg/m(2)/剂量，每日2次，进行前瞻性、开放、多中心的I/II期研究。每4-12周监测一次安全性、病毒学和免疫学反应。结果：31例HIV感染者分为两个年龄组，14天至6周和6周至6个月；29例完成了48周的随访(中位数=123周，范围4-252)。在12个月大的时候，曲线下的LPV面积的中位数在两个年龄组中是相似的，与年龄较大的儿童和成年人相似。治疗48周时，31例患者中有22例(71%)HIV-1RNA含量为400拷贝/ml，11例(73%)HIV-1RNA含量为50拷贝/ml，29例患者在研究治疗时HIV-1RNA含量为400拷贝/ml，19例(66%)持续抑制至研究结束；病毒抑制与超过1微克/毫升LPV目标的时间点的百分比较高(92%对71%，P=0.002)。结论：作为CART方案的一部分，300/75 mg/m(2)/剂量的LPV/r300/75 mg/m(2)/剂量可使65%的婴幼儿在96周的治疗中获得病毒抑制。由于最初低剂量的LPV暴露在6周大的婴儿中，经常调整剂量以增加体重是可取的，应该考虑研究对非常年幼的婴儿使用更高的剂量。(C)2011年Wolters Kluwer Health垂直酒吧Lippincott Williams&Wilkins
Objective: To investigate the longitudinal pharmacokinetics, safety and efficacy of lopinavir/ritonavir (LPV/r) in HIV-infected infants initiating combination antiretroviral therapy (cART) between 2 weeks and 6 months of age.Method: A prospective, open-label, multicenter Phase I/II study of LPV/r-based cART at a dose of 300/75 mg/m(2)/dose LPV/r twice daily. Intensive pharmacokinetic sampling at 12 months of age and quarterly predose LPV concentrations were collected and safety, virologic and immunologic responses were monitored every 4-12 weeks up to 252 weeks.Results: Thirty-one HIV-infected infants enrolled into two age cohorts, 14 days to < 6 weeks and 6 weeks to < 6 months; 29 completed >= 48 weeks of follow-up (median = 123 weeks, range 4-252). At 12 months of age, median LPV area under the curve was comparable for both age cohorts and similar to older children and adults. At week 48, 22 of 31 patients (71%) had HIV-1 RNA < 400 copies/ml and 11 of 15 (73%) had < 50 copies/ml; 29 of 31 achieved HIV-1 RNA < 400 copies/ml on study treatment and 19 (66%) remained durably suppressed until the end of study; viral suppression correlated with a higher percentage of predose time points exceeding the LPV target of 1 mu g/ml (92 vs. 71%, P=0.002).Conclusion: LPV/r at 300/75 mg/m(2)/dose as part of a cART regimen resulted in viral suppression through 96 weeks of treatment in > 65% of young infants. Due to initially low LPV exposure in infants < 6 weeks of age, frequent dose adjustment for weight gain is advisable and consideration should be given to studying a higher dose for very young infants. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins