Different pattern of stool and plasma gastrointestinal damage biomarkers during primary and chronic HIV infection

IntroductionPrimary HIV infection (PHI) is the initial phase after HIV acquisition characterized by high viral replication, massive inflammatory response and irreversible immune-damage, particularly at the gastrointestinal level. In this study we aimed to characterize the dynamics of gastrointestinal damage biomarkers during the different phases of HIV infection and assess their association with HIV-disease markers and their accuracy to differentiate PHI from chronic HIV infection (CHI).MethodsPHI-individuals (n = 57) were identified as HIV-seronegative/HIV-RNA positive and were followed up for one year at the Manhiça District Hospital in Mozambique. Ten plasma and 12 stool biomarkers were quantified by Luminex or ELISA and levels were compared to CHI-naive (n = 26), CHI on antiretroviral-treatment (ART; n = 30) and HIV-uninfected individuals (n = 58). Regression models adjusted by time point were used to estimate the association of the biomarkers with HIV-disease markers. Receiver operating curves were compared for the best accuracy to distinguish PHI from CHI.ResultsSoluble (s)CD14 was significantly associated with the CD4/CD8 ratio (P < 0.05) and viremia levels (P < 0.0001) during PHI. Plasma zonulin and stool lactoferrin were significantly higher in PHI as compared to CHI-individuals (P < 0.05). Plasma zonulin demonstrated the best accuracy to identify PHI among HIV-infected individuals (AUC = 0.85 [95% CI 0.75–0.94]). Using a cutoff value of plasma zonulin ≥ 8.75 ng/mL the model identified PHI with 87.7% sensitivity (95% CI 76.3–94.9) and 69.2% specificity (95% CI 48.2–85.7). An adjusted multivariate model including age, plasma zonulin and sCD14 further increased the classification performance (AUC = 0.92 [95% CI 0.86–0.99]).ConclusionsWhile the stool biomarkers did not provide any predictive ability to distinguish PHI from CHI-individuals, plasma sCD14 and zonulin were significantly associated with HIV-disease markers and PHI identification, respectively. These inflammatory biomarkers may be useful to monitor changes in gastrointestinal integrity during HIV infection.

初级 HIV 感染（PHI）是 HIV 感染后的初始阶段，其特征为病毒复制旺盛、大量炎症反应和不可逆的免疫损伤，特别是在胃肠道水平。本研究旨在描述 HIV 感染不同阶段胃肠道损伤生物标志物的动态变化，并评估其与 HIV 疾病标志物的关联及其区分 PHI 与慢性 HIV 感染（CHI）的准确性。方法：在莫桑比克马尼查区医院确定了 57 名 PHI 患者作为 HIV 阴性/HIV-RNA 阳性个体，并对其进行了为期一年的随访。通过 Luminex 或 ELISA 定量分析了 10 种血浆和 12 种粪便生物标志物，并将水平与 CHI 初次感染者（n = 26）、CHI 抗逆转录病毒治疗（ART；n = 30）和 HIV 未感染者（n = 58）进行了比较。通过时间点调整的回归模型来估算生物标志物与 HIV 疾病标志物的关联。比较受试者工作特征曲线以确定区分 PHI 和 CHI 的最佳准确性。结果：可溶性（s）CD14 与 CD4/CD8 比率（P < 0.05）和病毒血症水平（P < 0.0001）在 PHI 期间显著相关。与 CHI 患者相比，PHI 患者的血浆 zonulin 和粪便乳铁蛋白水平显著升高（P < 0.05）。血浆 zonulin 在 HIV 感染者中识别 PHI 的准确性最佳（AUC = 0.85 [95% CI 0.75–0.94]）。使用血浆 zonulin ≥ 8.75 ng/mL 的截止值，模型识别 PHI 的敏感性为 87.7%（95% CI 76.3–94.9），特异性为 69.2%（95% CI 48.2–85.7）。包括年龄、血浆 zonulin 和 sCD14 的调整多变量模型进一步提高了分类性能（AUC = 0.92 [95% CI 0.86–0.99]）。结论：尽管粪便生物标志物无法提供区分 PHI 与 CHI 患者的预测能力，但血浆 sCD14 和 zonulin 与 HIV 疾病标志物和 PHI 识别分别显著相关。这些炎症生物标志物可能有助于监测 HIV 感染期间胃肠道完整性的变化。