Protease inhibitors to reduce malaria in HIV-infected pregnant women

疟疾增加孕妇严重贫血、自然流产和胎儿死亡的风险; 低出生体重、贫血、发育不良和婴儿死亡率。这些 在艾滋病毒感染的情况下，疟疾的并发症更为严重。使用驱虫蚊帐 经杀虫剂处理过的蚊帐和抗叶酸剂治疗可以减少孕妇疟疾相关的发病率， 这些干预措施提供的保护远远不够。我们建议测试的假设， 艾滋病毒感染妇女在怀孕和哺乳期间战略性使用艾滋病毒蛋白酶抑制剂（PI）， 改善母婴结果。这一假设是基于疟疾寄生虫 和HIV表达生物化学上相似的蛋白酶，我们小组和其他人观察到HIV 发挥有效的体外抗疟疾活性。研究目的是： 1)确定基于PI的抗逆转录病毒治疗（ART）是否降低了产科和婴儿贫困的风险， 与非PI基础ART相比，感染艾滋病毒的孕妇的结局; 2)比较PI与非PI ART的母婴安全性和耐受性特征 怀孕和哺乳期间; 3)比较妊娠期间PI与非PI基础ART的病毒学和免疫学疗效 和母乳喂养 为了实现这些目标，我们将进行一项PI（洛匹那韦/利托那韦）与非PI（洛匹那韦/利托那韦）的随机、开放标签试验。 在500名妊娠28周内感染艾滋病毒的妇女中进行基于PI的抗逆转录病毒治疗。妇女和 将对婴儿进行6个月的哺乳期随访。主要研究终点将是胎盘风险 疟疾次要终点将包括婴儿低出生体重（<2500 g）、胎儿死亡和 晚期自然流产这项研究将在乌干达的托罗罗区进行， 疟疾传播。它将在一个公共卫生框架内进行， 目前是大多数撒哈拉以南非洲国家的标准护理策略; 甲氧苄啶磺胺甲恶唑和驱虫蚊帐。我们的目标是减少艾滋病毒和疟疾的负担， 改善母婴结果。

Malaria increases the risk of severe anemia, spontaneous abortion and fetal death in pregnant women; and low birth weight, anemia, poor developmental outcomes and mortality in their infants. These complications of malaria are amplified in the setting of HIV infection. The use of insecticide treated nets (ITNs) and antifolate therapy can reduce the malaria associated morbidity in pregnant women, but the protection afforded by these interventions is far from complete. We propose to test the hypothesis that the strategic use of HIV protease inhibitors (Pl)s during pregnancy and breastfeeding of HIV-infected women will improve maternal and infant outcomes. This hypothesis is based on the appreciation that malaria parasites and HIV express biochemically similar proteases and the observation by our group and others that HIV Pis exert potent in vitro antimalarial activity. Study aims are: 1) To determine if Pi-based antiretroviral therapy (ART) decreases the risk of poor obstetric and infant outcomes among HIV -infected pregnant women as compared to non-PI-based ART; 2) To compare the maternal and infant safety and tolerability profiles of PI versus non-Pi based ART during pregnancy and breastfeeding; 3) To compare the virologic and immunologic efficacy of PI versus non-Pi based ART during pregnancy and breastfeeding. To address these aims, we will conduct a randomized, open-label, trial of PI (lopinavir/ritonavir) vs. non- PI-based antiretroviral therapy among 500 HIV- infected women up to 28 weeks gestation. Women and infants will be followed through 6 months of lactation. The primary study endpoint will be the risk of placental malaria. Secondary endpoints will include a composite of infant low birth weight (<2500 g), fetal death and late spontaneous abortion. The study will be conducted in the Tororo district, Uganda, an area of high malaria transmission. It will be conducted in the context of a public health framework of proven preventive strategies that are currently the standard of care for most of sub-Saharan Africa; chemoprophylaxis with trimethoprim-sulfamethoxazole and ITNs. Our goal is to reduce the burden of HIV and malaria and to improve maternal and infant outcomes.