新疆伊犁州多状态Markov模型分析HIV/AIDS患者抗病毒治疗及影响因素

阿热祖·肉孜呢亚孜; 单濛; 胡晓敏; 何晓燕; 陈静; 倪明健

doi:10.11847/zgggws1140898

新疆伊犁州多状态Markov模型分析HIV/AIDS患者抗病毒治疗及影响因素

Disease progression and its influencing factors among HIV/AIDS patients on antiretroviral therapy in Yili, Xinjiang Uygur Autonomous Region: a multi-state Markov model analysis on follow-up data

摘要

摘要:
目的构建马尔科夫（Markov）模型分析HIV/AIDS接受抗病毒治疗（ART）后疾病进展情况及其影响因素。
方法选取2019年1月 — 2020年10月于新疆伊犁州伊宁市第二人民医院接受国家免费抗病毒治疗的 2000 例HIV感染者/艾滋病患者（HIV/AIDS）作为研究对象，开展随访18个月的前瞻性队列研究，构建基于CD4⁺ T淋巴细胞计数水平的连续时间离散状态的Markov模型分析艾滋病进展规律。艾滋病病程基于WHO的HIV相关免疫缺陷的CD4 + T淋巴细胞计数定义即无免疫缺陷（≥ 500个/μL）为状态S1，轻度免疫缺陷（350～499个/μL）为状态S2，中度免疫缺陷（200～349个/μL）为状态S3，重度免疫缺陷（≤ 199个/μL）为状态S4，死亡为状态S5。
结果有效分析1491例HIV/AIDS患者随访数据，总随访2224.5人年。转移状态S1总逗留时间最长，为201.34月；状态S1～S4转移至S5（死亡）的概率分析中，状态S4转移至死亡概率最大（0.117）。多因素分析结果显示，以 ≤ 30岁为参照，≥ 50岁者S1向S2转移的强度增加；与异性性传播相比，注射吸毒者S1→S2、S2→S3的转移强度较高（aHR = 1.66，95%CI = 1.37～2.01；aHR = 1.65，95%CI = 1.21～2.25），S2→S1、S3→S2的转移强度较低（aHR = 0.80，95%CI = 0.68～0.94；aHR = 0.73，95%CI = 0.58～0.92）；与基线CD4⁺ T淋巴细胞计数 ≥ 500个/μL相比，基线CD4⁺ T淋巴细胞计数为350～499、200～349和 ≤ 199个/μL者S1→S2的转移强度均高于基线CD4⁺ T淋巴细胞计数 ≥ 500个/μL者；基线CD4⁺ T淋巴细胞计数为350～499、200～349和 ≤ 199个/μL者S1→S2的强度均低于基线CD4⁺ T淋巴细胞计数 ≥ 500个/μL者。S2→S3时，基线CD4⁺ T淋巴细胞计数 < 200个/μL者转移强度高于基线CD4⁺ T淋巴细胞计数 ≥ 500个/μL者；WHO临床分期为Ⅱ期者的S2→S3的转移强度高于WHO临床分期为Ⅰ期者。
结论经过ART，HIV/AIDS更倾向于向相邻的免疫更好的状态转移，高龄（≥ 50岁）、感染途径为注射吸毒、基线CD4⁺ T淋巴细胞计数水平较低的患者免疫恶化的风险更大。

Abstract:
Objective To analyze disease progression and its influencing factors in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients on antiretroviral therapy (ART) with Markov modeling.
Methods We recruited a total of 2 000 HIV/AIDS patients (aged ≥ 16 years) receiving free ART at a public hospital in Yining city, Xinjiang Uygur Autonomous Region (Xinjiang) from 2019 through October 2020 for a 18-month follow-up study. CD4⁺T lymphocyte count of the patients were detected at the enrollment and subsequent follow-ups and four disease progression states of the patients were defined based on the count: namely S1, S2, S3, and S4 for the patients with the CD4⁺T lymphocyte count of ≥ 500/μL, 350 – 499/μL, 200 – 349/μL, and < 200/μL and the mortality was defined as S5. A continuous-time discrete-state Markov model was constructed based on the CD4⁺T lymphocyte count to analyze disease progression patterns of the patients.
Results The analysis finally included 1 491 HIV/AIDS patients on ART, with a total follow-up of 2 224.5 person-years. For all the patients, S1 showed the longest total persistent duration of 201.34 months and S4 was of the highest probability of mortality (0.17) compared to other states. The results of multifactorial analysis revealed following factors associated with the intensity of disease state transition: (1) increased intensity of transition from S1 to S2 for patients aged ≥ 50 years compared to those aged < 30 years; (2) higher intensity of transition from S1 to S2 (adjusted hazard ratio aHR = 1.66, 95% confidence interval 95%CI: 1.37 – 2.01) and from S2 to S3 (aHR = 1.65, 95%CI: 1.21 – 2.25) but lower intensity of transition from S2 to S1 (aHR = 0.80, 95%CI: 0.68 – 0.94) and from S3 to S2 (aHR = 0.73, 95%CI: 0.58 – 0.92) for the patients infected heterosexually compared to those infected via drug injection; (3) higher intensity of transition from S1 to S2 but lower intensity of transition from S2 to S1 for the patients with the baseline CD4⁺T lymphocyte count of 350 – 499/μL, 200 – 349/μL, and < 200/μL in comparison with the patients with the baseline CD4⁺T lymphocyte count of ≥ 500/μL; (4) stronger intensity of transition from S2 to S3 for the patients with the baseline CD4⁺T lymphocyte count of < 200/μL compared to the patients with the baseline CD4⁺T lymphocyte count of ≥ 500/μL; and (5) higher intensity of transition from S2 to S3 for the patients at World Health Organization HIV/AIDS stage II compared to those at the stage I.
Conclusion Better transition of disease state was observed in HIV/AIDS patients on ART in Yili city of Xinjiang ant the patients aged 50 years and above, infected via drug injection, and with lower baseline CD4⁺T lymphocyte count were at increased risk of deteriorative transition of disease state.

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