目标:开始抗逆转录病毒治疗(ART)后,HIV相关免疫重建炎症综合征(IRIS),一系列机会性感染表明,可能发生,提出要么自相矛盾,先前治疗过的感染恶化,或者揭开面具,一个潜在的爆发,以前未诊断的感染。ART作为艾滋病毒治疗和预防的支柱的影响延长了艾滋病毒感染者的生存期。在怀孕期间,减缓艾滋病毒进展和预防围产期传播已显示出益处;然而,ART存在不良反应的风险,包括对胎儿和母亲的免疫反应。这项研究试图估计HIV-IRIS的累积和类型的发病率,无论是矛盾的还是揭露的IRIS,确定基线母体和HIV临床标志物作为预测因子,并分析依赖CD4计数增加和/或病毒载量快速减少评估的IRIS结局的生存时间的对数秩检验。
方法:在2019年6月至2020年3月期间,在肯雅塔国家医院和姆巴加蒂医院的产前护理单位(ANCu)进行了一项活跃记录研究。内罗毕,肯尼亚。参与者的年龄在20至49岁之间,并且经过确认的HIV阳性检测。为了确定IRIS的真实案例,独立审查委员会对诊断的准确性和一致性进行了判定.血浆HIV病毒载量,CD4计数,和常规实验室评估(血红蛋白,每个医院的临床实验室进行白细胞计数(WBC))。在ART开始后的前三个月内,使用国际抗HIV相关IRIS研究网络(INSHI)评估了IRIS的发病率。以IRIS为结果的多变量Cox回归,使用SPSSSurvival包,检查了基线母体特征与ART开始前HIV临床标志物和IRIS之间的关系,最后,进行了预测IRIS的决策树分析。
结果:来自532名纯ART孕妇,133(25%)开发了IRIS,其中97人(72.9%)属于揭发类别。从第2周(风险比(HR)=0.0287)到第12周(HR=3.6158),经历IRIS症状的累积风险增加。基线时母亲BMI(MBMI)为25-29.9kg/m2的参与者暴露IRIS的风险更高(HR=2.478;P=0.010)。WHO-HIV临床阶段1和2向矛盾的IRIS倾斜(回归系数=-0.111和-0.276(P<0.05)),而阶段4则偏向于揭开IRIS(回归系数=0.047,HR=1.048,P=0.941)。CD4计数>500个细胞/mm^3偏向于揭开IRIS(回归系数=0.192,HR=1.211,P=0.416),而RNA-HIV病毒载量>50拷贝/ml,对矛盾的IRIS(回归系数=-0.199,HR=0.820,P=0.360。关于决策树分析,85%(P=0.001)的未接受ART治疗的孕妇的基线CD4计数低于500拷贝/mm^3表现为IRIS的掩蔽。
结论:对于初治ART的孕妇,解开虹膜是最常见的类型,MBMI为25-29.9kg/m2,晚期HIV感染,CD4计数<500个细胞/mm^3,基线时更高的奇偶校验可能是临床有用的预测因子.与矛盾的IRIS相比,未接受ART治疗的孕妇比例更高,因此需要根据潜在的预测因素进行早期评估。
OBJECTIVE: Following antiretroviral therapy (ART) initiation, HIV-associated immune reconstitution inflammatory syndrome (IRIS), indicated by an array of opportunistic infections, may occur, presenting as either paradoxical, a worsening of a previously treated infection, or unmasking, a flare-up of an underlying, previously undiagnosed infection. The impact of ART as the backbone of HIV treatment and prevention has prolonged the survival of people living with HIV. In pregnancy, benefits have been shown by slowing HIV progression and preventing perinatal transmission; however, there have been risks of adverse reactions with ART, including immune responses to both the fetus and mother. This
study sought to estimate the incidence of HIV-IRIS cumulatively and by type either paradoxical or unmasking IRIS, determine the baseline maternal and HIV clinical markers as predictors of, and analyze the log-rank test for survival time to IRIS outcome assessed by relying on an increase in CD4 count and/or a rapid decrease in viral load.
METHODS: An active records
study was conducted between June 2019 and March 2020 among ART-naïve pregnant women attending the antenatal care units (ANCu) at the Kenyatta National and Mbagathi Hospitals, Nairobi, Kenya. Participants were aged between 20 and 49 years and had a confirmed HIV-positive test. To ascertain a true case of IRIS, the diagnosis was adjudicated for accuracy and consistency by an independent review committee. Plasma HIV viral load, CD4 counts, and routine laboratory evaluations (hemoglobin, white blood cell count (WBC)) were performed by each hospital\'s clinical laboratory. The IRIS incidence was assessed using the International Network for Studies Against HIV-Associated IRIS (INSHI) during the first three months after ART initiation. Multivariate Cox regression with IRIS as the outcome, using the SPSSSurvival package, examined the relationship between baseline maternal characteristics and HIV clinical markers before ART initiation and IRIS, and finally, decision-tree analysis for predicting IRIS was performed.
RESULTS: From a pool of 532 ART-naïve pregnant women, 133 (25%) developed IRIS, and 97 (72.9%) were in the unmasking category. The accumulated risk of experiencing IRIS symptoms increased from week two (hazard ratio (HR)=0.0287) to week 12 (HR=3.6158). Participants with a maternal BMI (MBMI) of 25-29.9 kg/m2 at baseline were at a higher risk of unmasking IRIS (HR=2.478; P=0.010). The WHO-HIV clinical stages 1 and 2 skewed towards paradoxical IRIS (regression coefficients =-0.111 and -0.276 (P<0.05)), while stage 4 skewed towards unmasking IRIS (regression coefficient=0.047, HR=1.048, P=0.941). A CD4 count > 500 cells/mm^3 skewed towards unmasking IRIS (regression coefficient=0.192, HR=1.211, P=0.416), while RNA-HIV viral loads >50 copies/ml towards paradoxical IRIS (regression coefficient=-0.199, HR=0.820, P=0.360. On decision tree analysis, 85% (P=0.001) of ART-naïve pregnant women with a baseline CD4 count below 500 copies/mm^3 presented with unmasking IRIS.
CONCLUSIONS: For ART-naïve pregnant women, unmasking IRIS is the most common type, and an MBMI of 25-29.9 kg/m2, advanced HIV infection, a CD4 count <500 cells/mm^3, and a higher parity at baseline may be clinically useful predictors. The higher proportion of ART-naïve pregnant women experiencing unmasking as compared to paradoxical IRIS supports the need for earlier assessment based on potential predictors.