Division of Infectious Diseases, Children's Memorial Hospital, Northwestern University's Feinberg School of Medicine, Chicago, Illinois, USA.
AIDS. 2011 Mar 13;25(5):643-9. doi: 10.1097/QAD.0b013e32834403f6.
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.
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.
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 μg/ml (92 vs. 71%, P = 0.002).
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.
研究在 2 周龄至 6 月龄时开始联合抗逆转录病毒治疗（cART）的 HIV 感染婴儿中洛匹那韦/利托那韦（LPV/r）的纵向药代动力学、安全性和疗效。
一项前瞻性、开放标签、多中心的 LPV/r 为基础的 cART 的 I/II 期研究，剂量为 300/75mg/m2/LPV/r，每日两次。在 12 月龄时进行强化药代动力学采样，并在每 4-12 周收集一次 LPV 浓度的预剂量，监测安全性、病毒学和免疫学反应，直至 252 周。
31 名 HIV 感染婴儿分为两个年龄组，14 天至<6 周龄和 6 周至<6 月龄；29 名完成了≥48 周的随访（中位数=123 周，范围 4-252 周）。在 12 月龄时，两个年龄组的 LPV 曲线下面积相似，与较大儿童和成人相似。在第 48 周时，31 名患者中有 22 名（71%）的 HIV-1 RNA<400 拷贝/ml，11 名（73%）的 HIV-1 RNA<50 拷贝/ml；31 名患者中有 29 名在研究治疗中实现了 HIV-1 RNA<400 拷贝/ml，19 名（66%）持续抑制至研究结束；病毒抑制与更高比例的预剂量时间点超过 LPV 目标值 1μg/ml 相关（92%比 71%，P=0.002）。
LPV/r 以 300/75mg/m2/剂量作为 cART 方案的一部分，在 >65%的幼儿中可在 96 周的治疗中实现病毒抑制。由于在<6 周龄的婴儿中 LPV 最初暴露量较低，因此建议根据体重增加频繁调整剂量，并应考虑为非常年幼的婴儿研究更高剂量。
