Prendergast Andrew J, Chasekwa Bernard, Rukobo Sandra, Govha Margaret, Mutasa Kuda, Ntozini Robert, Humphrey Jean H
Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
J Infect Dis. 2017 Sep 15;216(6):651-661. doi: 10.1093/infdis/jix367.
Disease progression is rapid in human immunodeficiency virus (HIV)-infected infants. Whether intestinal damage and inflammation underlie mortality is unknown.
We measured plasma intestinal fatty acid binding protein (I-FABP), soluble CD14 (sCD14), interleukin 6 (IL-6), and C-reactive protein (CRP) at 6 weeks and 6 months of age in 272 HIV-infected infants who either died (cases) or survived (controls), and in 194 HIV-exposed uninfected (HEU) and 197 HIV-unexposed infants. We estimated multivariable odds ratios for mortality and postnatal HIV transmission for each biomarker using logistic regression.
At 6 weeks, HIV-infected infants had higher sCD14 and IL-6 but lower I-FABP than HIV-exposed and HIV-unexposed infants (P < .001). CRP was higher in HIV-exposed than HIV-unexposed infants (P = .02). At 6 months, HIV-infected infants had highest sCD14, IL-6, and CRP concentrations (P < .001) and marginally higher I-FABP than other groups (P = .07). CRP remained higher in HIV-exposed vs HIV-unexposed infants (P = .04). No biomarker was associated with mortality in HIV-infected infants, or with odds of breast-milk HIV transmission in HIV-exposed infants.
HIV-infected infants have elevated inflammatory markers by 6 weeks of age, which increase over time. In contrast to adults and older children, inflammatory biomarkers were not associated with mortality. HEU infants have higher inflammation than HIV-unexposed infants until at least 6 months, which may contribute to poor health outcomes.
人类免疫缺陷病毒(HIV)感染婴儿的疾病进展迅速。肠道损伤和炎症是否是导致死亡的原因尚不清楚。
我们在272例死亡(病例组)或存活(对照组)的HIV感染婴儿、194例暴露于HIV但未感染(HEU)婴儿和197例未暴露于HIV婴儿6周和6个月龄时,测量了血浆肠道脂肪酸结合蛋白(I-FABP)、可溶性CD14(sCD14)、白细胞介素6(IL-6)和C反应蛋白(CRP)。我们使用逻辑回归估计每个生物标志物的死亡率和产后HIV传播的多变量比值比。
6周时,HIV感染婴儿的sCD14和IL-6高于暴露于HIV和未暴露于HIV的婴儿,但I-FABP低于后者(P < 0.001)。暴露于HIV的婴儿CRP高于未暴露于HIV的婴儿(P = 0.02)。6个月时,HIV感染婴儿的sCD14、IL-6和CRP浓度最高(P < 0.001),I-FABP略高于其他组(P = 0.07)。暴露于HIV的婴儿CRP仍高于未暴露于HIV的婴儿(P = 0.04)。没有生物标志物与HIV感染婴儿的死亡率相关,也与暴露于HIV婴儿的母乳HIV传播几率相关。
HIV感染婴儿在6周龄时炎症标志物升高,且随时间增加。与成人和大龄儿童不同,炎症生物标志物与死亡率无关。HEU婴儿至少在6个月前的炎症高于未暴露于HIV的婴儿,这可能导致不良健康结局。