背景：隨著高效能抗愛滋病毒藥物治療(highly active antiretroviral therapy, HAART)的普遍使用，愛滋病朝向慢性病發展，愛滋病毒感染者與非感染者相比餘命差距不大。但由於慢性發炎及免疫活化影響，愛滋病毒感染者經歷提早老化，增加非傳染性疾病風險，其中包括中風。愛滋病毒感染者及帶狀疱疹感染者都會增加罹患中風的風險，但若同時感染兩者對於罹患中風的機制尚不明確。愛滋病毒感染者因為免疫低下，與一般人相比合併帶狀疱疹的機率較高。目前愛滋病毒合併帶狀疱疹感染者罹患中風風險及相關危險因子的研究較少。
目的：本研究旨在探討全球愛滋病毒感染者感染帶狀疱疹之發生率及相關危險因子、另外比較HIV感染者以及對照組在合併帶狀疱疹後罹患中風之風險及危險因子。
研究方法：第一階段進行高效能抗愛滋病毒藥物治療對於降低愛滋病毒感染者帶狀疱疹風險之系統性文獻回顧及統合分析，搜尋2000年至2021年2月發表之中英文文獻，資料庫包括：Embase、PubMed、Cochrane Library及 CINAHL等，所有文獻皆需有帶狀疱疹發生率之數據，並以Critical Appraisal Skills Program (CASP)作為品質評估工具，使用固定效應模式計算帶狀疱疹發生率及相關危險因子。第二階段採全人口巢式病例對照研究設計，於2000-2017年全民健保資料庫中，病歷組選取HIV 感染者罹患中風，對照組則以1:10的比例隨機選取與病歷組配對年齡、性別及中風診斷日之HIV感染者無罹患中風。本研究估算HIV感染者以及對照組合併帶狀疱疹感染後罹患中風之風險，透過邏輯斯迴歸模式估算HIV 感染者其合併帶狀疱疹與發生中風之相關。
結果：首先，系統性文獻及統合分析結果指出愛滋病毒感染者服用高效能抗愛滋病毒藥物治療後，帶狀疱疹發生率約2.3/百人年(95% CI: 1.56-3.05)。相關危險因子為男性(adjusted odds ratio [AOR]: 4.35, 95% CI: 1.72-11.13)、CD4數值小於200(AOR: 11.59, 95% CI: 1.70-79.84)及未服用HAART藥物(AOR: 2.89, 95% CI: 0.64-12.94)。其次，健保資料庫全人口研究中發現，愛滋病毒合併帶狀疱疹感染者罹患中風風險約1.85倍(95% CI:1.42-2.41)。影響愛滋病毒感染者合併高血壓(AOR: 3.53, 95% CI: 2.86–4.34)、心臟疾病(AOR: 2.32, 95% CI: 1.54–3.48)、慢性腎臟疾病(AOR: 1.82, 95% CI: 1.16-2.85)、C型肝炎(AOR: 1.49, 95% CI: 1.22–1.83)、高血脂(OR: 1.41, 95% CI: 1.12–1.78)及使用蛋白質酶抑制劑者(AOR: 1.33, 95% CI: 1.05–1.69)罹患中風風險顯著較高。
結論：我們研究結果指出愛滋病毒感染者服用高效能抗愛滋病毒藥物治療能降低帶狀疱疹的發生率，而愛滋病人合併帶狀疱疹感染將增加中風風險。未來將持續努力讓愛滋病毒感染者確立診斷後立即給予高效能抗愛滋病毒藥物治療，擬定愛滋病毒感染者預防中風之計劃，尤其是合併帶狀疱疹感染更需提早進行介入。

Background: The incidence of stroke was increasing among the younger people with human immunodeficiency virus (HIV), and herpes zoster (HZ) may increase the risk of stroke. However, the exact mechanisms underlying this relationship are poorly understood. Few studies have focused on HZ-induced risk of stroke among HIV-infected patients in the highly active antiretroviral therapy, (HAART) era. Recognition of stroke incidence in patients with HIV and HZ is hampered by limited knowledge of strokes and the associated risk factors.
Purpose: The meta-analysis aimed to estimate the global incidence and risk factors related to herpes zoster among people living with HIV in the HAART era. The nested case-control study aimed to estimate the incidence of stroke, and identify associated factors with risks of stroke among a cohort of people living with HIV.
Method: A systematic review and a meta-analysis was conducted to estimate the incidence rate and risk factors for herpes zoster among the HIV population in the HAART era. We reviewed Chinese and English articles from Embase, PubMed, Cochrane Library, and the Cumulative Index to Nursing and Allied Health (CINAHL), as well as databases for studies published in Chinese and English from January 2000 to March 2021. The study quality was assessed using the Critical Appraisal Skills Program (CASP) appraisal tool. A random-effect model was used to calculate pooled estimates of HZ incidence rates. In part II, a nested case-control study was conducted using the Nationwide National Health Insurance Research Database (NHIRD) from 2000 to 2017 containing HIV registered. A total of 509 stroke cases were 1:10 matched to 5090 controls on age (±5 years), sex, and date of first stroke diagnosis. Logistic regression models were used to estimate the odds ratio and 95% Confidence interval (CI) of the study outcomes. IRB approval was obtained before data collection.
Results: Initially, the pooled incidence of HZ among the HIV population in the HAART era was 2.30 (95% CI: 1.56–3.05) per 100 person years (PYs). The risks of incidence of HZ among people living with HIV included male sex (adjusted odds ratio [AOR]: 4.35, 95% CI: 1.72–11.13), CD4 count < 200 cells/µL (AOR: 11.59, 95% CI: 1.70–79.84) and not receiving HAART (AOR: 2.89, 95% CI: 0.64–12.94). Secondly, the odds ratio of stroke was significantly higher in the HIV-infected population with HZ (AOR: 1.85, 95% CI: 1.42–2.41). A significantly increased AOR of stroke was associated with hypertension (AOR: 3.53, 95% CI: 2.86–4.34), heart disease (AOR: 2.32, 95% CI: 1.54–3.48), chronic kidney disease (AOR: 1.82, 95% CI: 1.16-2.85), hepatitis C virus infection (AOR: 1.49, 95% CI: 1.22–1.83), hyperlipidemia (OR: 1.41, 95% CI: 1.12–1.78), and treatment with protease inhibitors (AOR: 1.33, 95% CI: 1.05–1.69).
Conclusion and implication: Our findings highlight a lower incidence of HZ among HIV infected patients receiving HAART than those not receiving HAART, and HZ co-infection with HIV is associated with higher stroke risks. It requires sustained effort in initiating HAART immediately after diagnosis to treat all HIV-positive individuals and suggesting the interventions in people living with HIV to prevent stroke, especially those with HZ co-infection.

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