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首页> 外文期刊>The New England journal of medicine >Antiretroviral agents and prevention of malaria in HIV-infected ugandan children
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Antiretroviral agents and prevention of malaria in HIV-infected ugandan children

机译：抗逆转录病毒试剂和预防艾滋病毒感染的乌干达儿童疟疾

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BACKGROUND: Human immunodeficiency virus (HIV) protease inhibitors show activity against Plasmodium falciparum in vitro. We hypothesized that the incidence of malaria in HIV-infected children would be lower among children receiving lopinavir-ritonavir-based antiretroviral therapy (ART) than among those receiving nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based ART. METHODS:We conducted an open-label trial in which HIV-infected children 2 months to 5 years of age who were eligible for ART or were currently receiving NNRTI-based ART were randomly assigned to either lopinavir-ritonavir-based ART or NNRTI-based ART and were followed for 6 months to 2 years. Cases of uncomplicated malaria were treated with artemether-lumefantrine. The primary end point was the incidence of malaria. RESULTS: We enrolled 176 children, of whom 170 received the study regimen: 86 received NNRTI-based ART, and 84 lopinavir-ritonavir-based ART. The incidence of malaria was lower among children receiving the lopinavir-ritonavir-based regimen than among those receiving the NNRTI-based regimen (1.32 vs. 2.25 episodes per person-year; incidence-rate ratio, 0.59; 95% confidence interval [CI], 0.36 to 0.97; P = 0.04), as was the risk of a recurrence of malaria after treatment with artemether-lumefantrine (28.1% vs. 54.2%; hazard ratio, 0.41; 95% CI, 0.22 to 0.76; P = 0.004). The median lumefantrine level on day 7 after treatment for malaria was significantly higher in the lopinavir-ritonavir group than in the NNRTI group. In the lopinavir-ritonavir group, lumefantrine levels exceeding 300 ng per milliliter on day 7 were associated with a reduction of more than 85% in the 63-day risk of recurrent malaria. A greater number of serious adverse events occurred in the lopinavir-ritonavir group than in the NNRTI group (5.6% vs. 2.3%, P = 0.16). Pruritus occurred significantly more frequently in the lopinavir-ritonavir group, and elevated alanine aminotransferase levels significantly more frequently in the NNRTI group. CONCLUSIONS: Lopinavir-ritonavir-based ART as compared with NNRTI-based ART reduced the incidence of malaria by 41%, with the lower incidence attributable largely to a significant reduction in the recurrence of malaria after treatment with artemether-lumefantrine. Lopinavir-ritonavir-based ART was accompanied by an increase in serious adverse events. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT00978068.)
机译：背景：人免疫缺陷病毒（HIV）蛋白酶抑制剂显示出对恶性疟原虫体外活性。我们推测疟疾的感染艾滋病毒的儿童发病率将接收儿童比那些接受非核苷类逆转录酶抑制剂（NNRTI）为基础的技术为基础的洛匹那韦，利托那韦抗逆转录病毒疗法（ART）的比例较低。方法：我们进行了一项开放标签试验中，感染艾滋病毒的儿童2个月至5岁谁有资格ART或目前正在接受NNRTI为基础的艺术被随机分配到基于洛匹那韦，利托那韦ART或基于NNRTI ART和随访6个月至2年。简单的疟疾病例为蒿甲醚 - 本芴醇治疗。初级终点是疟疾的发病率。结果：我们招收176名儿童，其中170接收到的研究方案：86接受NNRTI为基础的艺术，而84为基础的洛匹那韦，利托那韦艺术。疟疾的发病率儿童接受比那些接收NNRTI为基础的方案（每人年1.32 2.25对比发作洛匹那韦，利托那韦，基于方案中更低;发病率比率，0.59; 95％置信区间[CI] ，0.36〜0.97; P = 0.04），因为是疟疾的复发的风险蒿甲醚 - 本芴醇（28.1％对54.2％治疗后;风险比，0.41; 95％CI，0.22至0.76; P = 0.004） 。治疗疟疾后第7天平均水平本芴醇是洛匹那韦，利托那韦组比NNRTI组显著高。在洛匹那韦，利托那韦基，苯芴醇含量超过300每毫升纳克在第7天用在复发性疟疾的63日风险降低了超过85％相关联。严重不良事件的更大数量发生的洛匹那韦，利托那韦组中比在NNRTI组（5.6％对2.3％，P = 0.16）英寸瘙痒发生显著更频繁的洛匹那韦，利托那韦组中，和NNRTI组显著更频繁谷丙转氨酶升高的水平。结论：与NNRTI为基础的技术相比，基于洛匹那韦，利托那韦ART了41％降低了疟疾的发病率，与下发生率很大程度上归因于与蒿甲醚 - 苯芴醇处理后在疟疾的复发显著减少。基于洛匹那韦，利托那韦艺术是伴随着增加严重不良事件。 （由儿童健康和人类发展的尤尼斯·肯尼迪·施莱佛国立研究所资助; ClinicalTrials.gov号码，NCT00978068）

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    AchanJ.; KakuruA.; IkileziG.; RuelT.; ClarkT.D.; NsanzabanaC.; CharleboisE.; AweekaF.; DorseyG.; RosenthalP.J.; HavlirD.; KamyaM.R.;

  • 作者单位

    Department of Pediatrics and Child Health Makerere University College of Health Sciences;

    Makerere University College of Health Sciences Infectious Diseases Research Collaboration Kampala;

    Makerere University College of Health Sciences Infectious Diseases Research Collaboration Kampala;

    Department of Pediatrics University of California San Francisco San Francisco United States;

    Department of Medicine University of California San Francisco San Francisco United States;

    Department of Medicine University of California San Francisco San Francisco United States;

    Department of Medicine University of California San Francisco San Francisco United States;

    Clinical Pharmacy Drug Research Unit University of California San Francisco San Francisco;

    Department of Medicine University of California San Francisco San Francisco United States;

    Department of Medicine University of California San Francisco San Francisco United States;

    Department of Medicine University of California San Francisco San Francisco United States;

    Department of Medicine Makerere University College of Health Sciences Infectious Diseases;

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