Systemic Inflammation and the Increased Risk of Inflamm-Aging and Age-Associated Diseases in People Living With HIV on Long Term Suppressive Antiretroviral Therapy
Systemic Inflammation and the Increased Risk of Inflamm-Aging and Age-Associated Diseases in People Living With HIV on Long Term Suppressive Antiretroviral Therapy
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DOI：
10.3389/fimmu.2019.01965
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发表时间：
2019-08-27
影响因子：
7.3
通讯作者：
Neogi, Ujjwal
中科院分区：
文献类型：
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作者：
Babu, Hemalatha;Ambikan, Anoop T.;Neogi, Ujjwal
印度等中低收入国家的抗逆转录病毒疗法项目遵循公共卫生方法，为所有艾滋病毒感染者（PLHIV）提供标准化治疗方案。根据来自高收入国家（HIC）的证据，在艾滋病毒感染者中观察到了早衰或年龄相关疾病的风险增加和加重。然而，在使用第一代抗艾滋病毒药物（如齐多夫定和拉米夫定）的人群中，关于残留炎症和免疫激活的数据非常有限，这些药物具有更多的毒副作用。因此，本研究的目的是使用大量炎症和免疫激活的生物标志物来评估全身炎症的水平，并了解PLHIV长期抑制性ART中年龄相关疾病的风险。血液样品获自未经治疗的PLHIV（Pre-ART，n = 43）、接受ART>5年的PLHIV（ART，n = 53）和HIV阴性健康对照（HIVNC，n = 41）。对样本进行了92种炎症标志物、sCD 14、sCD 163和端粒长度的分析。进行了几项统计检验，以比较研究中的各组。采用多元线性回归分析研究相关性。尽管ART成功的中位持续时间为8年，但与HIVNC相比，ART组的sCD 14（p < 0.001）和sCD 163（p = 0.04）水平继续显著升高。发现11种炎性标志物，包括4 E-BP 1、ADA、CCL 23、CD 5、CD 8A、CST 5、MMP 1、NT 3、SLAMF 1、TRAIL和TRANCE，在组间存在显著差异（p < 0.05）。这些标志物中的许多与年龄相关的共病相关，包括心血管疾病、神经认知下降，其中一些标志物是首次在HIV诱导的炎症背景下报道的。线性回归分析显示HIV-1阳性与端粒长度呈显著负相关（p < 0.0001）。在ART组中，CXCL 1（p = 0.048）和TGF-α（p = 0.026）显示与端粒长度增加显著相关，IL-10 RA与端粒长度减少显著相关（p = 0.042）。这一观察结果值得进一步的机制研究，以产生证据，强调需要加强对艾滋病毒感染者的治疗监测和特别干预。
The ART program in low- and middle-income countries (LMIC) like India, follows a public health approach with a standardized regimen for all people living with HIV (PLHIV). Based on the evidence from high-income countries (HIC), the risk of an enhanced, and accentuated onset of premature-aging or age-related diseases has been observed in PLHIV. However, very limited data is available on residual inflammation and immune activation in the populations who are on first-generation anti-HIV drugs like zidovudine and lamivudine that have more toxic side effects. Therefore, the aim of the present study was to evaluate the levels of systemic inflammation and understand the risk of age-associated diseases in PLHIV on long-term suppressive ART using a large number of biomarkers of inflammation and immune activation. Blood samples were obtained from therapy naive PLHIV (Pre-ART, n = 43), PLHIV on ART for >5 years (ART, n = 53), and HIV-negative healthy controls (HIVNC, n = 41). Samples were analyzed for 92 markers of inflammation, sCD14, sCD163, and telomere length. Several statistical tests were performed to compare the groups under study. Multivariate linear regression was used to investigate the associations. Despite a median duration of 8 years of successful ART, sCD14 (p < 0.001) and sCD163 (p = 0.04) levels continued to be significantly elevated in ART group as compared to HIVNC. Eleven inflammatory markers, including 4E-BP1, ADA, CCL23, CD5, CD8A, CST5, MMP1, NT3, SLAMF1, TRAIL, and TRANCE, were found to be significantly different (p < 0.05) between the groups. Many of these markers are associated with age-related co-morbidities including cardiovascular disease, neurocognitive decline and some of these markers are being reported for the first time in the context of HIV-induced inflammation. Linear regression analysis showed a significant negative association between HIV-1-positivity and telomere length (p < 0.0001). In ART-group CXCL1 (p = 0.048) and TGF-alpha (p = 0.026) showed a significant association with the increased telomere length and IL-10RA was significantly associated with decreased telomere length (p = 0.042). This observation warrants further mechanistic studies to generate evidence to highlight the need for enhanced treatment monitoring and special interventions in HIV-infected individuals.