Lopinavir/ritonavir + zidovudine to prevent perinatal HIV in Thailand

项目总结 对于资源有限的情况，世界卫生组织建议艾滋病毒感染者 不需要为自己的健康而治疗的孕妇接受齐多夫定(ZDV)治疗 妊娠28周，分娩时单剂奈韦拉平(NVP)，48-72岁婴儿 预防艾滋病毒母婴传播(母婴传播)的生命小时。这个养生法是 安全，并将传播风险降低到？2%，但这与NVP的选择有关 母亲和受感染儿童的耐药性突变。这些突变已经被证明是 降低后续基于NVP的治疗的有效性。在工业化国家，更多 使用高效抗逆转录病毒疗法(HAART)联合治疗的复杂方案 怀孕传播率也很低，同时避免了抗性的选择 突变为NVP。 这项研究将在多中心、III期、随机对照的临床试验中比较 一种简单、经济、有效的ZDV+组合的有效性、安全性和可行性 Lopinavir/ritonavir(LPV/r)从妊娠28周开始与目前推荐的方案比较 由世卫组织在非母乳喂养人群中传播。 具体目标是评估和比较这两种方法：(1) 艾滋病毒传播(通过DNA-PCR检测婴儿艾滋病毒状况)；(2)具有临床意义的发病率 妇女和婴儿的不良事件，以及妇女的CD4和病毒载量的演变； 艾滋病毒耐药性突变的发生率。LPV/r在泰国孕妇体内的药代动力学 也将接受评估。如果被证明与目前世卫组织的治疗方案一样有效和安全 防止母婴传播，这一方案将提供一种选择，以保持低风险的围产期传播和 解决NVP耐药突变给母亲和受感染儿童带来的困境， 从而保留他们未来的治疗选择。 这项研究将在NIH资助的临床试验中增加第三个臂，该试验评估了另一种策略 解决NVP耐药突变问题，即孕期和婴儿ZDV 与世界卫生组织方案(R01 HD 052461)相比，仅有NVP。这项三臂临床试验将 对2097名自愿接受HIV-1感染的孕妇进行CD4计数和250个/mm3的跟踪调查 由43家泰国公立医院组成的网络中的婴儿在分娩后24个月内出生(每臂699名) 包括5%的不可评估；5%的阿尔法；80%的能力；非劣势测试的增量：1.5%)。

PROJECT SUMMARY For resource-limited settings, the World Health Organization recommends that HIV infected pregnant women who do not need treatment for their own health receive zidovudine (ZDV) from 28 weeks' gestation, with single dose nevirapine (NVP) at onset of labor and in infants at 48-72 hours of life for the prevention of mother to child transmission (PMTCT) of HIV. This regimen is safe and reduces the risk of transmission to ?2%, but it is associated with the selection of NVP resistance mutations in mothers and infected children. These mutations have been shown to diminish the efficacy of subsequent NVP based therapies. In industrialized countries, more complex regimens using highly active antiretroviral therapy (HAART) combinations during pregnancy also achieve very low transmission rates while avoiding the selection of resistance mutations to NVP. The study will compare in a multicenter, phase III, randomized controlled, clinical trial the efficacy, safety, and feasibility of a simple, affordable and potent combination of ZDV + lopinavir/ritonavir (LPV/r) from 28 weeks' gestation versus the regimen currently recommended by WHO in a non breastfeeding population. The specific objectives are to evaluate and compare between the two approaches: (1) the risk of HIV transmission (infant HIV status by DNA-PCR); (2) the incidence of clinically significant adverse events in women and infants, and the CD4 and viral load evolution in women; (3) the incidence of HIV resistance mutations. The pharmacokinetics of LPV/r in Thai pregnant women will also be assessed. If proved to be as efficacious and safe as the current WHO regimen for PMTCT, this regimen will provide an option to maintain a low risk of perinatal transmission and resolve the dilemma posed by NVP resistance mutations for both mothers and infected children, thereby preserving their future treatment options. The study will add a third arm to an NIH funded clinical trial, which evaluates another strategy to resolve the problem of NVP resistance mutations, i.e. ZDV from 28 weeks' gestation and infant only NVP compared to the WHO regimen (R01 HD 052461). This three arm clinical trial will follow 2097 consenting HIV-1 infected pregnant women with CD4 count >250/mm3 and their infants in a network of 43 Thai public hospitals up to 24 months after delivery (n=699 per arm including 5% non evaluable; alpha 5%; power: 80%; delta for non-inferiority testing: 1.5%).