de Souza Campos Fernandes Regina Célia, Louvain de Souza Thaís, da Silva Barcellos Thiago, Medina-Acosta Enrique
Faculty of Medicine of Campos, Campos dos Goytacazes, Brazil.
Municipal Program for the Surveillance of Sexually Transmitted Diseases and Acquired Immunodeficiency Syndrome of Campos dos Goytacazes, Campos dos Goytacazes, Brazil.
Front Pediatr. 2019 Jul 10;7:293. doi: 10.3389/fped.2019.00293. eCollection 2019.
In human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) patients with very low CD4 cell counts, there is a temporal relationship between administration of antiretroviral therapy (ART) and an increased inflammatory response state known as the immune reconstitution inflammatory syndrome (IRIS). The predominant clinical presentation of IRIS is an infectious disease that can be life-threatening. IRIS-related infectious events are distributed similarly between adult males and females, albeit a few studies have shown a skewing toward the male sex in pediatric IRIS. Here, we assessed sex-specific differences in the causes and extent of IRIS infectious events in HIV-infected pediatric patients on ART. We carried out a prospective clinical analysis (from 2000 to 2018) of IRIS-related infectious events after ART in a cohort of 82 Brazilian children and adolescents infected with HIV-1 through mother-to-child transmission as well as a comprehensive cross-referencing with public records on IRIS-related infectious causes in pediatric HIV/AIDS. Twelve events fulfilling the criteria of IRIS occurred exclusively in 11 females in our cohort. The median age at IRIS events was 3.6 years. The infectious causes included , varicella-zoster virus, molluscum contagiosum virus, human papillomavirus, cytomegalovirus, and . In one female, there was regional bacillus Calmette-Guérin dissemination and cytomegalovirus esophagitis. There was complete health recovery after 10 IRIS events without the use of corticosteroids or ART interruption. One case of IRIS-associated miliary tuberculosis was fatal. The biological female sex was a significant risk factor for IRIS events (odds ratio: 23.67; 95% confidence interval 95%: 1.341-417.7; = 0.0016 and < 0.01 by the multivariable analysis). We observed an effect of the advanced HIV/AIDS variable in IRIS females as compared with non-IRIS females (mean CD4 T cell percentage 13.36 vs. 18.63%; = 0.0489 and < 0.05 by the multivariable analysis), underpinning the exclusively skewed distribution toward the female sex of this cohort. Moreover, the IRIS females in our cohort had higher mean CD4 T cell percentages before (13.36%) and after IRIS (26.56%) than those of the IRIS females (before IRIS, 4.978%; after IRIS, 13.81%) in previous studies conducted worldwide. The exclusively skewed distribution of pediatric IRIS toward the female sex in the cohort was not linked to preferential X-chromosome inactivation rates. We concluded that the exclusively skewed distribution of pediatric IRIS toward females is associated with more advanced AIDS.
在人类免疫缺陷病毒和获得性免疫缺陷综合征（HIV/AIDS）患者中，当CD4细胞计数极低时，抗逆转录病毒疗法（ART）的使用与一种称为免疫重建炎症综合征（IRIS）的炎症反应状态增加之间存在时间关系。IRIS的主要临床表现是一种可能危及生命的传染病。与IRIS相关的感染事件在成年男性和女性中的分布相似，尽管有一些研究表明儿科IRIS中男性比例偏高。在此，我们评估了接受ART的HIV感染儿科患者中IRIS感染事件的原因和程度的性别差异。我们对82名通过母婴传播感染HIV-1的巴西儿童和青少年队列在接受ART后与IRIS相关的感染事件进行了前瞻性临床分析（从2000年至2018年），并与儿科HIV/AIDS中与IRIS相关的感染原因的公共记录进行了全面交叉参考。符合IRIS标准的12起事件仅发生在我们队列中的11名女性中。IRIS事件发生时的中位年龄为3.6岁。感染原因包括水痘带状疱疹病毒、传染性软疣病毒、人乳头瘤病毒、巨细胞病毒等。在一名女性中，出现了卡介苗局部播散和巨细胞病毒食管炎。10起IRIS事件后在未使用皮质类固醇或中断ART的情况下完全康复。1例与IRIS相关的粟粒性肺结核病例死亡。生物学女性性别是IRIS事件的一个显著危险因素（比值比：23.67；95%置信区间95%：1.341 - 417.7；多变量分析P = 0.0016且P < 0.01）。与非IRIS女性相比，我们观察到晚期HIV/AIDS变量在IRIS女性中有影响（平均CD4 T细胞百分比13.36%对18.63%；多变量分析P = 0.0489且P < 0.05），这支持了该队列中向女性的独特偏态分布。此外，我们队列中的IRIS女性在IRIS之前（13.36%）和之后（26.56%）的平均CD4 T细胞百分比高于全球先前研究中的IRIS女性（IRIS之前，4.978%；IRIS之后，13.81%）。该队列中儿科IRIS向女性的独特偏态分布与优先的X染色体失活率无关。我们得出结论，儿科IRIS向女性的独特偏态分布与更晚期的艾滋病有关。
