Protease inhibitors for prevention of malaria in HIV-infected children

在非洲，五岁以下儿童同时感染艾滋病毒和疟疾的负担最重。 即使每天使用甲氧苄啶-磺胺甲恶唑（TS）预防和杀虫剂处理的蚊帐， （驱虫蚊帐），疟疾在生活在疟疾高发地区的艾滋病毒感染儿童中仍然非常常见 传输强度抗逆转录病毒蛋白酶抑制剂（PI）洛匹那韦在体外抑制恶性疟原虫， 低于使用标准剂量的洛匹那韦/利托那韦（LPV/r）在血清中达到的那些。在这项研究中，我们将 检验使用基于PI的抗逆转录病毒疗法（ART）将降低疟疾发病率的假设 与非核苷逆转录酶（NNRTI）为基础的ART相比， 乌干达的疟疾高发区。这项研究的三个具体目标是： 1.比较接受PI与基于NNRTI的ART的HIV感染儿童的疟疾发病率 2.比较PI与基于NNRTI的ART的安全性和耐受性 3.比较PI与基于NNRTI的ART的病毒学和免疫学疗效 这项研究将是一项随机开放标签试验，300名艾滋病毒感染的乌干达儿童，6个月至5岁， 年龄符合乌干达和世界卫生组织开始抗逆转录病毒治疗的标准。该研究将于 乌干达托罗罗是疟疾传播强度高的地区。主要研究终点为 有症状的疟疾发病率。次要终点包括并发疟疾的发病率， 贫血和无症状寄生虫血症的患病率，2级或以上不良事件的发生率，CD 4 细胞恢复和HIV RNA病毒抑制的流行。儿童将接受基于PI或NNRTI的治疗 ART并随访24个月。所有儿童都将接受TS预防和驱虫蚊帐。所有医疗护理 将在研究诊所提供，使用经过充分验证的疟疾诊断、治疗和随访方案。 这项研究将由一个在疟疾研究和护理方面具有丰富经验的小组进行。 感染艾滋病毒的儿童。 这项试验将在非洲最脆弱的国家之一测试一种预防疟疾的新策略。 人口。有针对性地使用Pis作为居住在以下地区的年轻艾滋病毒感染儿童的一线治疗： 疟疾流行地区可以大大降低这两种疾病的高发病率和死亡率。

In Africa, children less than five years of age bear the greatest burden of HIV and malaria co-infection. Even with the use of daily trimethoprim-sulfamethoxazole (TS) prophylaxis and insecticide treated bednets (ITNs), malaria remains very common in HIV-infected children that live in areas with high malaria transmission intensity. The antiretroviral protease inhibitor (PI) lopinavir inhibits P. falciparum in vitro at levels lower that those achieved in serum with standard dosing of lopinavir/ritonavir (LPV/r). In this study, we will test the hypothesis that the use of Pi-based antiretroviral therapy (ART) will reduce the incidence of malaria compared to non-nucleoside reverse transcriptase (NNRTI)-based ART among HIV-infected children living in a high malaria transmission area of Uganda. The three specific aims of this study are: 1. To compare the incidence of malaria among HIV-infected children receiving PI vs. NNRTI-based ART 2. To compare the safety and tolerability of PI vs. NNRTI-based ART 3. To compare the virologic and immunologic efficacy of PI vs. NNRTI-based ART The study will be a randomized open label trial of 300 HIV-infected Ugandan children, 6 months to 5 years of age that meet Ugandan and World Health Organization criteria for ART initiation. The study will take place in Tororo, Uganda a district with high malaria transmission intensity. The primary study endpoint will be the incidence of symptomatic malaria. Secondary endpoints include the incidence of complicated malaria, prevalence of anemia and asymptomatic parasitemia, incidence of adverse events grade 2 or greater, CD4 cell recovery and prevalence of HIV RNA viral suppression. Children will be treated with either PI- or NNRTIbased ART and followed for 24 months. All children will receive TS prophylaxis and ITNs. All medical care will be provided at the study clinic, using well validated protocols for malaria diagnosis, treatment and followup. The study will be conducted by a team with extensive experience in the study of malaria and care of HIV-infected children. This trial will test a novel strategy for the prevention of malaria in one of Africa's most vulnerable populations. The targeted use of Pis as first line therapy for young HIV-infected children that reside in malaria endemic regions could significantly reduce the high morbidity and mortality from both diseases.