Protease inhibitors to reduce malaria in HIV-infected pregnant women

疟疾会增加孕妇患严重贫血、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 在艾滋病毒感染的背景下，疟疾的并发症被放大。使用驱虫蚊帐 (ITNS)和抗叶酸治疗可以降低孕妇的疟疾相关发病率，但 这些干预措施提供的保护远未完成。我们建议检验这一假设 艾滋病毒感染妇女孕期和哺乳期战略使用艾滋病毒蛋白水解酶抑制剂S 改善母婴结局。这一假设是基于这样一种认识：疟疾寄生虫 和HIV表达生物化学相似的蛋白水解酶，我们小组和其他人观察到HIV Pis 发挥强大的体外抗疟疾活性。研究的目标是： 1)确定基于PI的抗逆转录病毒疗法(ART)是否降低产科和婴儿疾病的风险 感染艾滋病毒的孕妇与非基于PI的抗逆转录病毒疗法的结果比较； 2)比较PI与非PI ART的母婴安全性和耐受性 在怀孕和哺乳期间； 3)比较妊娠期PI与非PI ART的病毒学和免疫学效果。 还有母乳喂养。 为了达到这些目的，我们将进行一项随机、开放标签的PI(洛比那韦/利托那韦)与非 以PI为基础的抗逆转录病毒疗法对500名妊娠至28周的艾滋病毒感染妇女的治疗。女性和 婴儿将被跟踪6个月的哺乳期。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(&lt；2500克)、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，这是一个高海拔地区 疟疾传播。它将在经过证实的预防性公共卫生框架的背景下进行 目前是撒哈拉以南非洲大部分地区护理标准的战略；通过以下方式进行化学预防 甲氧苄氨嘧啶-磺胺甲恶唑和ITNS。我们的目标是减轻艾滋病毒和疟疾的负担，并 改善母婴结局。

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.