在联合抗逆转录病毒治疗中，CD4 T 细胞计数和基线时的可溶性程序性死亡受体-1 与 HIV/HBV 合并感染中乙型肝炎表面抗原下降相关。
CD4 T cell counts and soluble programmed death-1 at baseline correlated with hepatitis B surface antigen decline in HIV/HBV coinfection during combined antiretroviral therapy.
机构信息
Department of Infectious Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China.
出版信息
Front Cell Infect Microbiol. 2023 May 3;13:1178788. doi: 10.3389/fcimb.2023.1178788. eCollection 2023.
BACKGROUND
Several studies have described the rapid decline and clearance of hepatitis B surface antigen (HBsAg) in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfection after initiating combined antiretroviral therapy (cART). Early decline of HBsAg levels is associated with HBsAg seroclearance in the treatment of chronic HBV infection. This study aims to evaluate the HBsAg kinetics and the determinants of early HBsAg decline in patients with HIV/HBV coinfection during cART.
METHODS
A total of 51 patients with HIV/HBV coinfection were enrolled from a previously established HIV/AIDS cohort and followed for a median of 59.5 months after cART initiation. Biochemical tests, virology and immunology assessments were measured longitudinally. The kinetics of HBsAg during cART were analyzed. Soluble programmed death-1 (sPD-1) levels and immune activation markers (CD38 and HLA-DR) were measured at baseline, 1-year and 3-year during treatment. HBsAg response was defined as a decline of more than 0.5 log IU/ml at 6 months from the baseline after initiation of cART.
RESULTS
HBsAg declined faster (0.47 log IU/mL) in the first six months and attained a decrease of 1.39 log IU/mL after 5-year therapy. Seventeen (33.3%) participants achieved a decline of more than 0.5 log IU/ml at the first 6 months of cART(HBsAg response) of which five patients achieved HBsAg clearance at a median of 11 months (range: 6-51 months). Multivariate logistic analysis showed the lower baseline CD4 T cell levels (OR=6.633, =0.012) and sPD-1 level (OR=5.389, =0.038) were independently associated with HBsAg response after cART initiation. The alanine aminotransferase abnormality rate and HLA-DR expression were significantly higher in patients who achieved HBsAg response than in those who did not achieve HBsAg response after cART initiation.
CONCLUSION
Lower CD4 T cells, sPD-1, and immune activation were related to a rapid HBsAg decline in patients with HIV/HBV-coinfection after the initiation of cART. These findings imply that immune disorders induced by HIV infection may disrupt immune tolerance to HBV, leading to a faster decline in HBsAg levels during coinfection.
背景
几项研究描述了在开始联合抗逆转录病毒治疗（cART）后，人类免疫缺陷病毒（HIV）/乙型肝炎病毒（HBV）合并感染患者乙型肝炎表面抗原（HBsAg）的快速下降和清除。HBsAg 水平的早期下降与慢性 HBV 感染治疗中的 HBsAg 血清清除相关。本研究旨在评估 cART 期间 HIV/HBV 合并感染患者的 HBsAg 动力学和早期 HBsAg 下降的决定因素。
方法
从之前建立的 HIV/AIDS 队列中招募了 51 名 HIV/HBV 合并感染患者，并在 cART 开始后中位随访 59.5 个月。纵向测量了生化检查、病毒学和免疫学评估。分析了 cART 期间 HBsAg 的动力学。在基线、治疗 1 年和 3 年时测量了可溶性程序性死亡-1（sPD-1）水平和免疫激活标志物（CD38 和 HLA-DR）。HBsAg 反应定义为 cART 开始后 6 个月从基线下降超过 0.5 log IU/ml。
结果
在最初的 6 个月内，HBsAg 下降速度更快（0.47 log IU/mL），5 年后治疗后下降了 1.39 log IU/mL。17 名（33.3%）患者在 cART 的前 6 个月内下降超过 0.5 log IU/ml（HBsAg 反应），其中 5 名患者在中位数为 11 个月（范围：6-51 个月）时达到了 HBsAg 清除。多变量逻辑分析显示，较低的基线 CD4 T 细胞水平（OR=6.633，=0.012）和 sPD-1 水平（OR=5.389，=0.038）与 cART 启动后 HBsAg 反应独立相关。与 cART 启动后未达到 HBsAg 反应的患者相比，达到 HBsAg 反应的患者的丙氨酸氨基转移酶异常率和 HLA-DR 表达明显更高。
结论
在开始 cART 后，HIV/HBV 合并感染患者中较低的 CD4 T 细胞、sPD-1 和免疫激活与 HBsAg 的快速下降有关。这些发现表明，HIV 感染引起的免疫紊乱可能破坏了对 HBV 的免疫耐受，导致合并感染期间 HBsAg 水平更快下降。
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