人類免疫缺乏病毒感染（Human immunodeficiency virus infection, HIV infection）為全球重要傳染病之一，主要破壞人體免疫系統，使免疫功能下降，同時也會刺激人體免疫系統釋放許多細胞激素，致使病毒感染者處於長期慢性發炎反應狀態。抗病毒藥物雖可重建人體免疫功能，但對於減緩慢性發炎的效果卻很有限。過往研究顯示，長期服藥病毒控制良好的感染者，相較同齡非感染者仍有較高比例在較早年紀罹患心血管疾病、代謝症候群、骨質疏鬆等慢性疾病。The Veterans Aging Cohort Study （VACS）世代研究為美國始於1997年持續至今之多中心HIV感染者及非感染者長期世代追蹤研究，研究利用病毒感染者門診規則追蹤抽血項目建立VACS index，此指標項目包括年紀、CD4免疫球數目、HIV病毒量、腎功能及肝纖維化分數 （FIB-4）及合併HCV感染，將各分項分層計算分數後再加總，即為VACS index。研究顯示，VACS index總分和感染者長期預後，例如住院、5年死亡率、衰弱表型、認知功能缺損及骨折等不良預後相關。VACS index分數越高，預後越不好。
本研究納入1677位平均年紀42.2歲於成大醫院規則回診追蹤且診斷超過一年的病毒感染者，於2016至2022年間每半年計算VACS index分數，收集感染者至少一次至多十四次VACS index分數，共13366筆資料進行群組化軌跡模式分析。研究結果顯示病毒感染者分成三組：持續低分（678人，40.4%，VACS index 中位數0分）、持續中分（808人，48.2%，VACS index中位數16分）及持續高分（191人，11.4%，中位數52分）。相較持續低分及中分組，持續高分組的病毒感染者有較高比例慢性疾病發生及死亡，平均CD4免疫球數目較低且未達到病毒量測不到的比例較高。使用多變量羅吉斯迴歸方法及決策樹方法進行預測持續高分組相關因子分析，結果顯示年紀、非同志族群感染者、基期血色素、基期FIB-4指標及合併HCV感染為羅吉斯迴歸方法分析之相關因子；基期血色素低於12mg/dL、基期FIB-4高於1.1及年紀大於69歲為決策樹方法結果。研究並利用成大醫院感染者數據重新統計VACS index指標項目分數，調整版VACS index和原始VACS index分數呈現高度正相關。據文獻回顧結果，本研究為亞洲國家第一個使用VACS index軌跡分數變化研究病毒感染者長期預後的研究，結果提供照護醫師了解臨床照顧之病毒感染者VACS index分數變化軌跡及快速辨識高風險族群。針對持續高分組應安排相關預後評估並確認病毒治療成效，針對新診斷治療滿一年的病毒感染者，如血色素低於12mg/dL、FIB-4高於1.1或大於69歲以上年長者應多加留意。

HIV infection is one the important infectious disease around the world. It weakens human’s immunity. Meanwhile, it also induces the body’s immune system to release inflammatory cytokines and causes chronic inflammation. Effective antiretroviral therapy (ART) restores cellular immunity but its ability to reverse chronic inflammation is very limited. Previous studies found that PLWH (people living with HIV) suffered from higher incidence of cardiovascular disease, metabolic syndrome, osteoporosis at earlier age than non-PLWH despite ART use. The Veterans Aging Cohort Study (VACS) was a longitudinal, prospective observational cohort study conducted since 1997 and used routinely obtained generic data during clinic follow to generate the VACS index. Seven parameters, age, CD4 cell count, HIV-1 RNA, hemoglobin, creatinine, HCV status and FIB-4 score, were categorized into two to four levels with various scores, and the VACS index was the sum of all level-specific scores. The VACS index was correlated with poor outcome, such as mortality, hospitalization, phenotype frailty, neurocognitive function impairment and fracture. Higher scores indicative of worsen outcome.
This present study enrolled 1677 PLWH with an average age of 42.2 years old who were confirmed of HIV infection for more than one year and received regular follow-up at NCKUH. We calculated the VACS index for each patient every half year and each participant had at least one and at most 14 records during 2016~2022. Totally 13366 records were collected to do group-based trajectory analysis (GBTA). Through GBTA, 678 PLWH (40.4%) were categorized as the trajectory with consistently low VACS index (a median score of 0 point), 808 (48.2%) in the trajectory of consistently medium scores of the VACS index (median score, 16 points), and 191 PLWH (11.4%) were categorized into the group of consistently high scores of the VACS index (median score, 52 points). Comparing with the consistently-low and the consistently-medium group, the consistently high VACS index group had higher comorbidities, higher mortality, lower average CD4 cell count and higher proportion of detected HIV viral load. We then used multivariate logistic regression method and decision-tree (DT) method to evaluate the potential factors associated with unfavorable trajectory. Age, HIV exposure other than male-to-male sexual contact, baseline Hb level, FIB-4 and HCV co-infection were significantly associated with the unfavorable trajectory by the logistic regression method. On the other hand, Hb level below 12mg/dL, FIB-4 score higher than 1.0 and older than 69 years old were associated with the unfavorable trajectory by the DT method. We also recalculated the point values using NCKUH cohort and the revised VACS index was highly associated with the original VACS index. To the best of our knowledge from literature review, this is the first study to describe the clinical outcome and the VACS index of PLWH in Asia. The result of this study provided physicians with understanding of the long-term trajectories of the VACS index in PLWH. Physicians could identify the high risk PLWH quickly by using the VACS index. For the PLWH with the consistently-high VACS index, physicians need to consider more evaluations or interventions, and to assure drug adherence to address HIV control. For PLWH with newly confirmed of HIV who received ART for one year, more attentions should be paid to the PLWH with low Hb, high FIB-4 score, and low CD4 cell count.

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