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垂直感染艾滋病毒的儿童和青少年的低骨矿物质密度:危险因素以及T细胞活化和衰老的作用

Low Bone Mineral Density in Vertically HIV-infected Children and Adolescents: Risk Factors and the Role of T-cell Activation and Senescence.

作者信息

Jiménez Beatriz, Sainz Talía, Díaz Laura, Mellado María José, Navarro María Luisa, Rojo Pablo, González-Tomé María Isabel, Prieto Luis, Martínez Jorge, de José María Isabel, Ramos José Tomás, Muñoz-Fernandez María Ángeles

机构信息

From the *Department of Pediatrics, Health Research Institute San Carlos (IdISSC) and Facultad de Medicina, Hospital Universitario Clínico San Carlos, Madrid, Spain; †Department of Immunology, Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain; ‡Spanish HIV HGM BioBank; Health Research Institute Gregorio Marañón, Madrid, Spain; §Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain; ¶Department of Pediatrics, Infectious and Tropical Diseases, Hospital Universitario La Paz and IdiPaz, Madrid, Spain; ‖Pediatric Infectious Diseases Unit, Department of Pediatrics, Hospital General Universitario Gregorio Marañón, Madrid, Spain; **Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitario 12 de Octubre, Madrid, Spain; ††Department of Pediatrics, Hospital Universitario de Getafe, Getafe, Spain; and ‡‡Department of Pediatrics, Hospital Universitario Niño Jesús, Madrid, Spain.

出版信息

Pediatr Infect Dis J. 2017 Jun;36(6):578-583. doi: 10.1097/INF.0000000000001506.

Abstract

BACKGROUND

Our aim was to determine the prevalence and risk factors associated with low bone mineral density (BMD) in vertically HIV-infected patients and to investigate whether low BMD is related to immune activation and senescence induced by HIV infection.

METHODS

A cross-sectional study was performed in 98 vertically HIV-infected patients. BMD was measured by dual-energy radiograph absorptiometry at lumbar spine. Height adjustment of BMD Z score was performed using height-for-age Z score. T-cell immune activation and senescence were analyzed in a subgroup of 54 patients by flow cytometry.

RESULTS

Median age was 15.9 years, 71.4% were Caucasian, 99% received antiretroviral therapy and 80.6% had undetectable viral load. Low BMD (BMD Z score ≤ -2) was present in 15.3% of cases, but after height adjustment in 4.1% of cases. Height-adjusted BMD Z score was positively correlated with body mass index Z score, CD4/CD8 ratio and nadir CD4, and inversely with duration of severe immunosuppression and parathyroid hormone values. In the multivariate model including age, gender, ethnicity, encephalopathy, Tanner stage, nadir CD4, duration of viral suppression, CD4 count, CD4/CD8 ratio, body mass index, cumulative duration of antiretroviral therapy, tenofovir and protease inhibitors exposure, nadir CD4 was independently associated to height-adjusted BMD Z score. No association was found between height-adjusted BMD Z score and T-cell activation or senescence.

CONCLUSIONS

The prevalence of low BMD in vertically HIV-infected patients was low after height adjustment. Nadir CD4, but not T-cell activation or senescence, was an independent predictor for low BMD. Larger and prospective studies are needed to achieve better knowledge of the pathogenesis of low BMD in vertical HIV infection.

摘要

背景

我们的目的是确定垂直感染艾滋病毒患者中低骨矿物质密度(BMD)的患病率及相关危险因素,并研究低BMD是否与艾滋病毒感染诱导的免疫激活和衰老有关。

方法

对98例垂直感染艾滋病毒的患者进行了一项横断面研究。采用双能X线吸收法测量腰椎的骨密度。使用年龄别身高Z评分对BMD Z评分进行身高校正。通过流式细胞术对54例患者的亚组进行T细胞免疫激活和衰老分析。

结果

中位年龄为15.9岁,71.4%为白种人,99%接受抗逆转录病毒治疗,80.6%的病毒载量检测不到。15.3%的病例存在低BMD(BMD Z评分≤ -2),但身高校正后为4.1%。身高校正后的BMD Z评分与体重指数Z评分、CD4/CD8比值和最低CD4呈正相关,与严重免疫抑制持续时间和甲状旁腺激素值呈负相关。在包括年龄、性别、种族、脑病、坦纳分期、最低CD4、病毒抑制持续时间、CD4计数、CD4/CD8比值、体重指数、抗逆转录病毒治疗累计持续时间、替诺福韦和蛋白酶抑制剂暴露的多变量模型中,最低CD4与身高校正后的BMD Z评分独立相关。未发现身高校正后的BMD Z评分与T细胞激活或衰老之间存在关联。

结论

身高校正后,垂直感染艾滋病毒患者中低BMD的患病率较低。最低CD4是低BMD的独立预测因素,而非T细胞激活或衰老。需要开展更大规模的前瞻性研究,以更好地了解垂直艾滋病毒感染中低BMD的发病机制。

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