Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV - pilot study.
Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV - pilot study.
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DOI：
10.12688/wellcomeopenres.15563.2
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发表时间：
2020
影响因子：
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通讯作者：
Berkley JA
中科院分区：
文献类型：
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作者：
Kamau FW;Gwela A;Nyerere AK;Riitho V;Njunge JM;Ngari MM;Prendergast AJ;Berkley JA
背景：在低收入和中等收入国家，晚期艾滋病毒患者在开始抗逆转录病毒治疗（ART）后不久就会出现显着的死亡率。钙卫蛋白是对感染和炎症条件的先天反应的生物标志物。我们研究了 ART 治疗前收集的血浆钙卫蛋白与晚期 HIV 患者死亡率之间的关系。 方法：我们在肯尼亚两个地点开始 ART 时，对 HIV 感染成人和 13 岁以上青少年进行了一项试点病例队列研究，其中 CD4+ <100/mm3。在 REALITY 试验 (ISRCTN43622374) 中，除了 ART 之外，参与者还接受了三项析因随机干预措施。在基线（ART 之前）和治疗 4 周后收集的钙卫蛋白在 24 周内死亡的患者（病例）和随机选择的幸存者（非病例）的存档血浆中进行测量。使用带有逆采样概率权重的 Cox 比例风险模型评估与死亡率的关联，并根据年龄、性别、部位、BMI、病毒载量、随机治疗进行调整，并按 CD4+ 计数（0-24、25-49 和 50-99 个细胞/mm3）进行聚类。 结果：病例 (n=39) 中血浆钙卫蛋白基线中值 (IQR) 为 6.82 (2.65–12.5) µg/ml，非病例 (n=58) 中为 5.01 (1.92–11.5) µg/ml。基线钙卫蛋白与年龄、中性粒细胞计数和咳嗽的存在相关，但与其他测量的感染指标无关。在调整后的多变量模型中，基线钙卫蛋白与随后的死亡率相关：前 24 周和第 4 周内的死亡分别为 HR 1.64 (95% CI 1.11 - 2.42) 和 HR 2.77 (95% CI 1.58 - 4.88)。无论是否采取随机干预措施，病例和非病例的钙卫蛋白水平均在基线和 4 周之间下降。 结论：在肯尼亚开始 ART 的晚期 HIV 个体中，血浆钙卫蛋白可能有潜力作为早期死亡的生物标志物。需要在更大规模的研究中进行验证、与其他生物标志物进行比较以及对感染和炎症来源的调查。
Background: In advanced HIV, significant mortality occurs soon after starting antiretroviral treatment (ART) in low- and middle-incomes countries. Calprotectin is a biomarker of innate response to infection and inflammatory conditions. We examined the association between plasma calprotectin collected before ART treatment and mortality among individuals with advanced HIV. Methods: We conducted a pilot case-cohort study among HIV infected adults and adolescents over 13 years old with CD4+ <100/mm3 at ART initiation at two Kenyan sites. Participants received three factorial randomised interventions in addition to ART within the REALITY trial (ISRCTN43622374). Calprotectin collected at baseline (before ART) and after 4 weeks of treatment was measured in archived plasma of those who died within 24 weeks (cases) and randomly selected participants who survived (non-cases). Association with mortality was assessed using Cox proportional hazards models with inverse sampling probability weights and adjusted for age, sex, site, BMI, viral load, randomised treatments, and clustered by CD4+ count (0-24, 25-49, and 50-99 cells/mm3). Results: Baseline median (IQR) plasma calprotectin was 6.82 (2.65–12.5) µg/ml in cases (n=39) and 5.01 (1.92–11.5) µg/ml in non-cases (n=58). Baseline calprotectin was associated with age, neutrophil count and the presence of cough, but not other measured indicators of infection. In adjusted multivariable models, baseline calprotectin was associated with subsequent mortality: HR 1.64 (95% CI 1.11 - 2.42) and HR 2.77 (95% CI 1.58 - 4.88) for deaths during the first twenty-four and four weeks respectively. Calprotectin levels fell between baseline and 4 weeks among both cases and non-cases irrespective of randomised interventions. Conclusions: Among individuals with advanced HIV starting ART in Kenya, plasma calprotectin may have potential as a biomarker of early mortality. Validation in larger studies, comparison with other biomarkers and investigation of the sources of infection and inflammation are warranted.