Efficacy of artemisinin-based combination therapy (ACT) in people living with HIV (PLHIV) diagnosed with uncomplicated Plasmodium falciparum malaria in Africa: a WWARN systematic review.
Abena Takyi, Aboubakar Soma, Marianna Przybylska, Eli Harriss, Karen I Barnes, Prabin Dahal, Philippe J Guérin, Kasia Stepniewska, Verena I Carrara
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引用次数: 0
Abstract
Background: Africa bears the highest double burden of HIV and malaria worldwide. In 2023, an estimated 25.9 million people were living with HIV (PLHIV), and 246 million malaria cases were diagnosed in Africa. Malaria patients co-infected with HIV are considered at a higher risk of failing malaria treatment, according to the World Health Organization (WHO) guidelines. This systematic literature review aims to assess the treatment outcomes following artemisinin-based combination therapy (ACT) in PLHIV.
Methods: The literature search was conducted up to April 2022 in the following databases: MEDLINE, EMBASE, Web of Science, Cochrane Central, WHO Global Index Medicus, Clinicaltrials.gov, and the WorldWide Antimalarial Resistance Network (WWARN) Clinical Trial Library. Studies describing any malaria treatment outcomes or anti-malarial drug exposure in PLHIV treated for uncomplicated Plasmodium falciparum malaria infection were eligible for inclusion.
Results: A total of 26 articles describing 19 studies conducted between 2003 and 2017 in six countries were included in this review; it represented 2850 malaria episodes in PLHIV across various transmission settings. The most studied artemisinin-based combination was artemether-lumefantrine (in 16 studies). PLHIV were treated with various antiretroviral therapy (ART) regimens, namely efavirenz (EFV), nevirapine (NVP), atazanavir-ritonavir (ATVr), lopinavir-ritonavir (LPV/r), and/or on prophylaxis with trimethoprim-sulfamethoxazole (TS), or were untreated (in 3 studies). There was no evidence of an increased risk of recrudescence in PLHIV compared to those without HIV. When treated with artemether-lumefantrine, PLHIV receiving LPV/r had a lower risk of malaria recurrence compared to PLHIV on NVP-based or EFV-based ART, or those without HIV. LPV/r increased lumefantrine exposure and EFV-treated patients had a reduced exposure to both artemether and lumefantrine; NVP reduced artemether exposure only.
Conclusions: Limited data on ACT outcomes or drug exposure in PLHIV in Africa remains a reality to date, and the effect of antivirals appears inconsistent in the literature. Considering the heterogeneity in study designs, these review's findings support conducting an individual patient data meta-analysis to explore the impact of antiretroviral therapy on anti-malarial treatment.
Trial registration: The protocol for the original search was published on PROSPERO with registration number CRD42018089860.
背景：非洲是世界上艾滋病毒和疟疾双重负担最重的地区。2023年，非洲估计有2590万人感染艾滋病毒（PLHIV），并诊断出2.46亿疟疾病例。根据世界卫生组织（世卫组织）的指导方针，合并感染艾滋病毒的疟疾患者被认为有更高的疟疾治疗失败的风险。本系统文献综述旨在评估以青蒿素为基础的联合治疗（ACT）对PLHIV的治疗效果。方法：检索截至2022年4月的文献，检索数据库为：MEDLINE、EMBASE、Web of Science、Cochrane Central、WHO Global Index Medicus、Clinicaltrials.gov和世界抗疟药网络（WWARN）临床试验图书馆。描述无并发症恶性疟原虫疟疾感染的PLHIV治疗的任何疟疾治疗结果或抗疟疾药物暴露的研究均符合纳入条件。结果：本综述共纳入了26篇文章，描述了2003年至2017年间在6个国家进行的19项研究；在各种传播环境中，它代表了艾滋病毒感染者的2850例疟疾病例。以青蒿素为基础的组合研究最多的是蒿甲醚-甲苯芳碱（16项研究）。PLHIV患者接受各种抗逆转录病毒治疗（ART）方案，即依非韦伦（EFV）、奈韦拉平（NVP）、阿扎那韦-利托那韦（ATVr）、洛匹那韦-利托那韦（LPV/r），和/或使用甲氧苄啶-磺胺甲恶唑（TS）进行预防，或不接受治疗（3项研究）。与未感染HIV的患者相比，没有证据表明PLHIV患者复发的风险增加。当使用蒿甲醚-氨苯曲明治疗时，与基于nvp或基于efv的抗逆转录病毒治疗的PLHIV或未感染HIV的PLHIV相比，接受LPV/r治疗的PLHIV的疟疾复发风险较低。LPV/r增加了氨芳汀暴露，efv治疗的患者暴露于蒿甲醚和氨芳汀均减少；NVP仅减少蒿甲醚暴露。结论：迄今为止，关于非洲PLHIV患者ACT结果或药物暴露的有限数据仍然是一个现实，而且抗病毒药物的效果在文献中似乎不一致。考虑到研究设计的异质性，这些综述的发现支持进行个体患者数据荟萃分析，以探索抗逆转录病毒治疗对抗疟疾治疗的影响。试验注册：原始检索的方案已在PROSPERO上发布，注册号为CRD42018089860。
期刊介绍：
Malaria Journal is aimed at the scientific community interested in malaria in its broadest sense. It is the only journal that publishes exclusively articles on malaria and, as such, it aims to bring together knowledge from the different specialities involved in this very broad discipline, from the bench to the bedside and to the field.
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