PACTG P1030: LOPINAVIR/RITONAVIR IN HIV-1 INFECTED INFANTS < 6 MONTHS OF AGE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这项PACTG研究将有助于确定洛匹那韦/利托那韦（LPV/RTV）的适当剂量范围，并评估6个月以下婴儿对治疗的反应。 洛匹那韦/利托那韦在成人和6个月以上儿童的临床试验中显示出显著的抗病毒活性和耐受性。 在抗逆转录病毒治疗的HIV感染成人中，LPV 400 mg/RTV 100 mg BID联合治疗产生的平均LPV谷浓度（Ctrough）比野生型HIV的EC 50高50倍以上。 相比之下，对于目前可用的蛋白酶抑制剂（PI），在人血清存在下的Ctrough/EC 50比率<4。 这是一项I/II期、开放标签、剂量探索研究，样本量为12名14天以上6个月以下的HIV感染婴儿，其中至少3名婴儿不足6周。 方案为洛匹那韦300 mg/m2 /利托那韦75 mg/m2 / BID和2种核苷逆转录酶抑制剂（NRTI）。 治疗将持续至最后一例受试者入组后24个月。 本研究将评价LPV/RTV剂量要求，以提供与已证明在较大儿童和成人中安全有效的全身暴露量相似的全身暴露量。 它还将确定在6个月以下婴儿中开始LPV/RTV的短期和长期安全性和耐受性，作为包括（NRTI）的方案的一部分。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This PACTG study will help to identify an appropriate dose range of lopinavir/ritonavir (LPV/RTV) and evaluate response to therapy in infants less than 6 months of age. Lopinavir/ritonavir has shown significant antiviral activity and tolerability in clinical trials in adults and children >6 months of age. In antiretroviral-nanve HIV-infected adults, the combination of LPV 400 mg/RTV 100 mg BID produces a mean LPV trough concentration (Ctrough) which is more than 50 times higher than the EC50 of wild-type HIV. In comparison, the Ctrough/EC50 ratio in the presence of human serum for currently available protease inhibitors (PIs) is <4. This is a Phase I/II, open-label, dose finding study with a sample size of 12 HIV-infected infants older than 14 days and less than 6 months with at least three of the infants being less than 6 weeks. The regimen is Lopinavir 300mg/m2 / Ritonavir 75 mg/m2 / BID and 2 nucleoside reverse transcriptase inhibitors (NRTIs). Treatment will continue until 24 months after the last subject is enrolled. The study will evaluate the LPV/RTV dose requirements to provide systemic exposure similar to that which has been shown to be safe and effective in older children and adults. It will also determine the short-term and long-term safety and tolerability of LPV/RTV initiated in infants less than 6 months old as part of a regimen including (NRTIs).