Gasasira Anne F, Kamya Moses R, Achan Jane, Mebrahtu Tsedal, Kalyango Joan N, Ruel Theodore, Charlebois Edwin, Staedke Sarah G, Kekitiinwa Adeodata, Rosenthal Philip J, Havlir Diane, Dorsey Grant
Department of Internal Medicine, Makerere University, Mulago Hospital, Kampala, Uganda.
Clin Infect Dis. 2008 Apr 1;46(7):985-91. doi: 10.1086/529192.
Artemisinin-based combination therapies are rapidly being adopted for the treatment of malaria in Africa; however, there are limited data on their safety and efficacy among human immunodeficiency virus (HIV)-infected populations.
We compared malaria treatment outcomes between cohorts of HIV-infected and HIV-uninfected children in Uganda who were observed for 18 and 29 months, respectively. Malaria was treated with artesunate plus amodiaquine, and outcomes were assessed using standardized guidelines. HIV-infected children received trimethoprim-sulfamethoxazole prophylaxis and antiretroviral therapy in accordance with current guidelines.
Twenty-six HIV-infected participants experiencing 35 episodes of malaria and 134 HIV-uninfected children experiencing 258 episodes of malaria were included in the study. Twelve HIV-infected children were receiving antiretroviral therapy, 11 of whom were receiving zidovudine. Malaria treatment was highly efficacious in both the HIV-infected and HIV-uninfected cohorts (28-day risk of recrudescence, 0% and 3.6%, respectively); however, there was a trend towards increased risk of recurrent malaria among the HIV-uninfected children (2.9% vs. 13.2%; p = .08). Importantly, the risk of neutropenia 14 days after initiation of treatment with artesunate plus amodiaquine was higher among HIV-infected children than among HIV-uninfected children (45% vs. 6%; p < .001). The severity of all episodes of neutropenia in HIV-uninfected children was mild to moderate, and 16% of episodes of neutropenia in the HIV-infected cohort were severe or life-threatening (neutrophil count, <750 cells/mm(3)). In the HIV-infected cohort, the risk of neutropenia was significantly higher among children who received antiretroviral therapy than among those who did not receive antiretroviral therapy (75% vs. 26%; p < .001).
Artesunate plus amodiaquine was highly efficacious for malaria treatment in HIV-infected children but was associated with a high risk of neutropenia, especially in the context of concurrent antiretroviral use. Our findings highlight an urgent need for evaluation of alternative antimalarial therapies for HIV-infected individuals.
基于青蒿素的联合疗法正在非洲迅速被采用用于治疗疟疾；然而，关于其在人类免疫缺陷病毒（HIV）感染人群中的安全性和疗效的数据有限。
我们比较了乌干达分别观察18个月和29个月的HIV感染儿童队列与未感染HIV儿童队列的疟疾治疗结果。疟疾采用青蒿琥酯加阿莫地喹进行治疗，并使用标准化指南评估结果。HIV感染儿童根据现行指南接受甲氧苄啶 - 磺胺甲恶唑预防和抗逆转录病毒治疗。
本研究纳入了26名经历35次疟疾病例的HIV感染参与者和134名经历258次疟疾病例的未感染HIV儿童。12名HIV感染儿童正在接受抗逆转录病毒治疗，其中11名正在接受齐多夫定治疗。青蒿琥酯加阿莫地喹对HIV感染和未感染HIV的队列中的疟疾治疗均高度有效（28天复发风险分别为0%和3.6%）；然而，未感染HIV的儿童中复发性疟疾风险有增加趋势（2.9%对13.2%；p = 0.08）。重要的是，青蒿琥酯加阿莫地喹治疗开始后14天，HIV感染儿童中性粒细胞减少的风险高于未感染HIV的儿童（45%对6%；p < 0.001）。未感染HIV儿童所有中性粒细胞减少发作的严重程度为轻度至中度，而HIV感染队列中16%的中性粒细胞减少发作严重或危及生命（中性粒细胞计数<750个细胞/mm³）。在HIV感染队列中，接受抗逆转录病毒治疗的儿童中性粒细胞减少风险显著高于未接受抗逆转录病毒治疗的儿童（75%对26%；p < 0.001）。
青蒿琥酯加阿莫地喹对HIV感染儿童的疟疾治疗高度有效，但与中性粒细胞减少的高风险相关，尤其是在同时使用抗逆转录病毒药物的情况下。我们的研究结果突出了迫切需要评估针对HIV感染个体的替代抗疟疗法。
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