Lopinavir/ritonavir + zidovudine to prevent perinatal HIV in Thailand

洛匹那韦/利托那韦齐多夫定在泰国预防围产期艾滋病毒

• 批准号: 8104056
• 负责人: MARC J LALLEMANT
• 金额: $ 25.33万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-10 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8104056
• 关键词: AIDS prevention; Adverse event; Anti-Retroviral Agents; Applications Grants; Asia; Breast Feeding; CD4 Lymphocyte Count; Cesarean section; Child; Clinical Trials; Combined Modality Therapy; Complex; Consent; DNA; Developed Countries; Dose; Drug Combinations; Drug Kinetics; Enzymes; Evaluable Disease; Evolution; Female of child bearing age; Fetus; France; Funding; Future; Goals; Guidelines; HIV; HIV prevention trial; HIV-1; Health; Height; Hepatitis B Prevalence; Highly Active Antiretroviral Therapy; Hospitals; Hour; Immune; Immunocompromised Host; Incidence; Individual; Infant; Infant formula; Infection; International; Interruption; Labor Onset; Lamivudine; Lead; Life; Lopinavir/Ritonavir; Mothers; Mutation; NNRTI-resistance; Nevirapine; Oral; Perinatal; Pharmaceutical Preparations; Phase; Population; Postpartum Period; Pregnancy; Pregnant Women; Prevention; Prevention Guidelines; Prevention strategy; Prophylactic treatment; Public Health; Public Hospitals; Publishing; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Recommendation; Regimen; Resistance; Resources; Rest; Risk; Safety; Second Pregnancy Trimester; Testing; Thailand; Time; United States National Institutes of Health; Universities; Vertical Disease Transmission; Viral; Viral Load result; Woman; World Health Organization; Zidovudine; acronyms; antiretroviral therapy; arm; base; clinical research site; clinically significant; comparative efficacy; cost; feeding; head-to-head comparison; minimal risk; neonate; nevirapine resistance; non-nucleoside reverse transcriptase inhibitors; prevent; resistance mutation; risk selection; transmission process

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%).

项目摘要 对于资源有限的环境，世界卫生组织建议， 不需要为自身健康进行治疗的孕妇接受齐多夫定（ZDV）， 妊娠28周，分娩开始时和婴儿48-72岁时单剂量奈韦拉平（NVP） 艾滋病毒的母婴传播（PMTCT）。这种养生法是 安全，并降低传播的风险？2%，但与NVP的选择有关 母亲和受感染儿童的耐药性突变。这些突变已被证明 降低后续基于NVP的治疗的疗效。在工业化国家， 使用高效抗逆转录病毒治疗（HAART）组合的复杂方案， 怀孕也实现了很低的传播率，同时避免了选择性耐药 突变为NVP。 该研究将在一项多中心、III期、随机对照临床试验中比较 ZDV +的简单、可负担和有效组合的有效性、安全性和可行性 从妊娠28周开始的洛匹那韦/利托那韦（LPV/r）与目前推荐的方案 在非母乳喂养人群中。 具体目标是对这两种方法进行评价和比较：（1） 艾滋病毒传播（通过DNA-PCR检测婴儿艾滋病毒状况）;（2）临床显著 妇女和婴儿的不良事件，以及妇女的CD 4和病毒载量演变;（3） 艾滋病毒耐药突变的发生率。LPV/r在泰国孕妇中的药代动力学 也将被评估。如果被证明与目前的WHO方案一样有效和安全， 预防母婴传播，这一方案将提供一种选择，以维持低风险的围产期传播， 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。 这项研究将为NIH资助的临床试验增加第三个分支，该临床试验评估另一种策略， 解决NVP抗性突变的问题，即来自28周妊娠和婴儿的ZDV 仅NVP与WHO方案相比（R 01 HD 052461）。该三组临床试验将 对2097名同意的HIV-1感染孕妇（CD 4计数>250/mm 3）及其 在43家泰国公立医院的网络中，分娩后24个月内的婴儿（每组n=699 包括5%不可评价; α 5%;把握度：80%;非劣效性检验的δ：1.5%）。