Dignitas International, Zomba, Malawi.
Public Health and Nutrition Research Group, Kamuzu University of Health Sciences, Mangochi, Malawi.
Malar J. 2023 Jan 27;22(1):32. doi: 10.1186/s12936-023-04466-w.
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.
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).
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).
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.
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。
≥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。
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)。
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。