Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland.
Byramjee Jeejeebhoy Medical College, Johns Hopkins Clinical Research Site, Pune.
Clin Infect Dis. 2018 Sep 14;67(7):1103-1109. doi: 10.1093/cid/ciy253.
Preterm birth (PTB) rates are high in human immunodeficiency virus (HIV)-infected populations, even when on treatment. Still, only a subset of all births in HIV-infected pregnant women result in PTB, suggesting that risk factors other than HIV infection itself are also important. Inflammation is a known risk factor in uninfected populations, but its role in HIV-infected population have not been studied; in addition, the immune pathways involved are not clear and noninvasive immune markers with predictive value are lacking. Our objective was to determine the association of select markers of inflammation with PTB in HIV-1-infected pregnant women.
Within a randomized trial of pregnant women receiving nevirapine (Six-Week Extended-Dose Nevirapine [SWEN] trial), we nested a case-control study (n = 107; 26 cases, 81 controls) to determine the association of maternal inflammation with PTB. Cases were defined as PTB (<37 weeks' gestational age). We assessed inflammation by measuring plasma levels of markers of general inflammation (C-reactive protein [CRP]), intestinal barrier dysfunction (intestinal fatty acid binding protein [I-FABP]), and microbial translocation/monocyte activation (soluble CD14 [sCD14] and CD163 [sCD163]). Multivariable logistic regression was used to determine the odds of PTB per log2 increase of each marker.
In multivariable models, there was increased odds of PTB per unit increase of log2 sCD14 (adjusted odds ratio [aOR], 2.45; 95% confidence interval [CI], 1.24-4.86), log2 sCD163 (aOR, 3.87; 95% CI, 1.43-10.49), and log2 I-FABP (aOR, 2.28; 95% CI, 1.18-4.41) but not log2 CRP (aOR, 0.72; 95% CI, .48-1.09).
Our results show that select immune markers can identify women at higher risk for PTB in HIV-1-infected populations and suggest that modulating gut barrier integrity and microbial translocation may affect PTB.
NCT00061321.
尽管在接受治疗的情况下，人类免疫缺陷病毒（HIV）感染者的早产（PTB）率仍然很高。然而，在所有 HIV 感染孕妇的分娩中，只有一部分导致了 PTB，这表明除了 HIV 感染本身之外，还有其他风险因素也很重要。炎症是未感染人群的已知风险因素，但它在 HIV 感染人群中的作用尚未得到研究；此外，涉及的免疫途径尚不清楚，缺乏具有预测价值的非侵入性免疫标志物。我们的目的是确定选择的炎症标志物与 HIV-1 感染孕妇 PTB 的关系。
在接受奈韦拉平的孕妇随机试验（六周延长剂量奈韦拉平[SWEN]试验）中，我们嵌套了一项病例对照研究（n = 107；26 例，81 例对照），以确定母体炎症与 PTB 的关系。病例定义为 PTB（<37 周妊娠龄）。我们通过测量血浆中一般炎症标志物（C 反应蛋白[CRP]）、肠屏障功能障碍标志物（肠脂肪酸结合蛋白[I-FABP]）和微生物易位/单核细胞激活标志物（可溶性 CD14 [sCD14]和 CD163 [sCD163]）来评估炎症。多变量逻辑回归用于确定每个标志物的每对数增加单位与 PTB 的比值比。
在多变量模型中，sCD14 对数增加一个单位与 PTB 的比值比（调整比值比[aOR]，2.45；95%置信区间[CI]，1.24-4.86）、sCD163 对数增加一个单位（aOR，3.87；95% CI，1.43-10.49）和 I-FABP 对数增加一个单位（aOR，2.28；95% CI，1.18-4.41）均增加，但 CRP 对数增加一个单位（aOR，0.72；95% CI，.48-1.09）则不然。
我们的结果表明，一些免疫标志物可以识别出 HIV-1 感染人群中 PTB 风险较高的妇女，并表明调节肠道屏障完整性和微生物易位可能会影响 PTB。
NCT00061321。
