Suppr超能文献

ART 在马拉维抗逆转录病毒治疗成人中的疗效。

Artemether-lumefantrine efficacy among adults on antiretroviral therapy in Malawi.

机构信息

Dignitas International, Zomba, Malawi.

Public Health and Nutrition Research Group, Kamuzu University of Health Sciences, Mangochi, Malawi.

出版信息

Malar J. 2023 Jan 27;22(1):32. doi: 10.1186/s12936-023-04466-w.

Abstract

BACKGROUND

When people with human immunodeficiency virus (HIV) infection (PWH) develop malaria, they are at risk of poor anti-malarial treatment efficacy resulting from impairment in the immune response and/or drug-drug interactions that alter anti-malarial metabolism. The therapeutic efficacy of artemether-lumefantrine was evaluated in a cohort of PWH on antiretroviral therapy (ART) and included measurement of day 7 lumefantrine levels in a subset to evaluate for associations between lumefantrine exposure and treatment response.

METHODS

Adults living with HIV (≥ 18 years), on ART for ≥ 6 months with undetectable HIV RNA viral load and CD4 count ≥ 250/mm were randomized to daily trimethoprim-sulfamethoxazole (TS), weekly chloroquine (CQ) or no prophylaxis. After diagnosis of uncomplicated Plasmodium falciparum malaria, a therapeutic efficacy monitoring was conducted with PCR-correction according to WHO guidelines. The plasma lumefantrine levels on day 7 in 100 episodes of uncomplicated malaria was measured. A frailty proportional hazards model with random effects models to account for clustering examined the relationship between participant characteristics and malaria treatment failure within 28 days. Pearson's Chi-squared test was used to compare lumefantrine concentrations among patients with treatment failure and adequate clinical and parasitological response (ACPR).

RESULTS

411 malaria episodes were observed among 186 participants over 5 years. The unadjusted ACPR rate was 81% (95% CI 77-86). However, after PCR correction to exclude new infections, ACPR rate was 94% (95% CI 92-97). Increasing age and living in Ndirande were associated with decreased hazard of treatment failure. In this population of adults with HIV on ART, 54% (51/94) had levels below a previously defined optimal day 7 lumefantrine level of 200 ng/ml. This occurred more commonly among participants who were receiving an efavirenz-based ART compared to other ART regimens (OR 5.09 [95% CI 1.52-7.9]). Participants who experienced treatment failure had lower day 7 median lumefantrine levels (91 ng/ml [95% CI 48-231]) than participants who experienced ACPR (190 ng/ml [95% CI 101-378], p-value < 0.008).

CONCLUSION

Recurrent malaria infections are frequent in this population of PWH on ART. The PCR-adjusted efficacy of AL meets the WHO criteria for acceptable treatment efficacy. Nevertheless, lumefantrine levels tend to be low in this population, particularly in those on efavirenz-based regimens, with lower concentrations associated with more frequent malaria infections following treatment. These results highlight the importance of understanding drug-drug interactions when diseases commonly co-occur.

摘要

背景

当人类免疫缺陷病毒(HIV)感染者(PWH)出现疟疾时,他们可能因免疫反应受损和/或药物相互作用改变抗疟药物代谢而导致抗疟治疗效果不佳。在接受抗逆转录病毒治疗(ART)的 PWH 队列中评估了青蒿琥酯-咯萘啶的治疗效果,并测量了部分患者第 7 天的咯萘啶水平,以评估咯萘啶暴露与治疗反应之间的关系。

方法

≥18 岁的 HIV 感染者(HIV 阳性),接受 ART 治疗≥6 个月,HIV RNA 病毒载量不可检测且 CD4 计数≥250/mm3,随机接受每日甲氧苄啶-磺胺甲噁唑(TS)、每周氯喹(CQ)或不进行预防。在确诊为无并发症的恶性疟原虫疟疾后,根据世卫组织指南进行了治疗效果监测。对 100 例无并发症疟疾的第 7 天血浆青蒿琥酯水平进行了测量。使用包含随机效应模型的脆弱性比例风险模型来分析参与者特征与 28 天内疟疾治疗失败之间的关系。Pearson's Chi-squared 检验用于比较治疗失败和充分临床及寄生虫学反应(ACPR)患者之间的青蒿琥酯浓度。

结果

186 名参与者在 5 年内共观察到 411 例疟疾发作。未经调整的 ACPR 率为 81%(95%CI 77-86)。然而,经 PCR 校正排除新发感染后,ACPR 率为 94%(95%CI 92-97)。年龄增长和居住在恩迪兰德区与治疗失败的风险降低有关。在这个接受 ART 的 HIV 阳性成人人群中,54%(51/94)的患者第 7 天青蒿琥酯水平低于先前定义的 200ng/ml 最佳水平。在接受依非韦伦为基础的 ART 治疗的患者中,这一比例高于其他 ART 方案(比值比 5.09[95%CI 1.52-7.9])。治疗失败的患者第 7 天的中位数青蒿琥酯水平(91ng/ml[95%CI 48-231])低于获得 ACPR 的患者(190ng/ml[95%CI 101-378],p 值<0.008)。

结论

在接受 ART 的 PWH 人群中,复发性疟疾感染很常见。AL 的 PCR 校正后疗效符合世卫组织可接受治疗效果的标准。然而,在该人群中,青蒿琥酯水平往往较低,特别是在接受依非韦伦为基础的方案治疗的患者中,较低的浓度与治疗后更频繁的疟疾感染有关。这些结果强调了在常见疾病同时发生时,了解药物相互作用的重要性。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验