Factors affecting immune reconstitution in HIV/AIDS patients after antiretroviral therapy
WU Hong1, XU Ke1, ZHANG Xingliang1, LI Xiting1, CHENG Wei2
1. Department of AIDS/STD Control and Prevention, Hangzhou Center for Disease Control and Prevention,Hangzhou, Zhejiang 310021, China; 2. Zhejiang Provincial Center for Disease Control and Prevention,Hangzhou, Zhejiang 310051, China
Abstract:Objective To investigate the immune reconstitution of HIV/AIDS patients and its influencing factors after receiving antiviral therapy (ART) in Hangzhou City, so as to provide insights into improving the treatment effects and quality of life in HIV/AIDS patients. Methods A retrospective cohort of HIV/AIDS patients who began antiviral treatment between January 1, 2016 and August 31, 2021 and had a baseline CD4+T lymphocyte (CD4) counts of less than 500 cells/μL or a baseline CD4/CD8+T lymphocyte (CD8) ratio of less than 0.8 in Hangzhou City was followed up until August 31, 2023. Demographic information, antiviral therapy in formation, CD4 counts, and CD4/CD8 were collected from the Chinese Disease Prevention and Control Information System. A good immune reconstitution was defined as having CD4≥500 cells/μL and CD4/CD8≥0.8. The immune reconstitution status of HIV/AIDS patients were analyzed, and factors affecting immune reconstitution were identified using a multivariable Cox proportional risk regression model. Results A total of 3 349 HIV/AIDS patients were enrolled, with a median age at ART of 31 (interquartile range, 20) years. There were 3 075 males (91.82%), 1 600 cases with college education and above (47.78%) and 2 455 cases at WHO clinical stage Ⅰ-Ⅱ(73.31%). There were 1 368 cases with good immune reconstitution, accounting for 40.85%, and the proportion of HIV/AIDS patients with good immune reconstitution that began ART in 2016 was the highest, reaching 51.90%. Multivariable Cox proportional risk regression model identified WHO clinical stage (Ⅰ-Ⅱ, HR=2.529, 95%CI: 2.023-3.162), timely ART (HR=1.196, 95%CI: 1.027-1.394), initial treatment regimen (TDF+3TC+NVP/EFV, HR=2.185, 95%CI: 1.891-2.524; integrase inhibitors, HR=8.509, 95%CI: 6.706-10.795), baseline CD4/CD8 (≥0.1, HR: 1.600-4.515, 95%CI: 1.061-6.661), baseline hemoglobin (<90 mg/dL, HR=0.327, 95%CI: 0.121-0.880), hepatitis B infection (HR=0.619, 95%CI: 0.457-0.840) and hepatitis C infection (HR=0.308, 95%CI: 0.099-0.956) as factors affecting immune reconstitution in HIV/AIDS patients. Conclusion The immune reconstitution in HIV/AIDS patients after ART is associated with WHO clinical stage, timely ART, initial treatment regimen, baseline CD4/CD8, baseline hemoglobin and hepatitis B or C infection.
[1] LIMA V D,REUTER A,HARRIGAN P R,et al.Initiation of antiretroviral therapy at high CD4+cell counts is associated with positive treatment outcomes[J].AIDS,2015,29(14):1871-1882. [2] LIU P T,TANG Z Z,LAN G H,et al.Early antiretroviral therapy on reducing HIV transmission in China:strengths,weaknesses and next focus of the program[J].Sci Rep,2018,8(1):1-7. [3] 郑锦雷,潘晓红,马瞧勤,等.MSM人群HIV/AIDS基线CD4水平与艾滋病抗病毒治疗效果的关系研究[J].预防医学,2017,29(12):1189-1192,1198. [4] TARANCON-DIEZ L,RULL A,HERRETO P,et al.Early antiretroviral therapy initiation effect on metabolic profile in vertically HIV-1-infected children[J].J Antimicrob Chemother,2021,76(11):2993-3001. [5] YANG X D,SU B,ZHANG X,et al.Incomplete immune reconstitution in HIV/AIDS patients on antiretroviral therapy:challenges of immunological non-responders[J].J Leukoc Biol,2020,107(4):597-612. [6] 杨小东,粟斌,张彤.HIV-1感染者免疫重建不良研究进展[J].国际病毒学杂志,2020,27(1):82-85. [7] 陈素庭,洪航,方挺,等.宁波市2010—2020年抗病毒治疗HIV/AIDS免疫重建情况及影响因素分析[J].中华流行病学杂志,2023,44(1):133-138. [8] KUFA T,SHUBBER Z,MACLEOD W,et al.CD4 count recovery and associated factors among individuals enrolled in the South African antiretroviral therapy programme:an analysis of national laboratory based data[J].PLoS One,2019,14(5):1-15. [9] ROUL H,MARY-KRAUSE M,GHOSN J,et al.CD4+cell count recovery after combined antiretroviral therapy in the modern combined antiretroviral therapy era[J].AIDS,2018,32(17):2605-2614. [10] 李国贤,韦慧芬,颜海燕,等.HIV感染者/AIDS患者基线指标对抗病毒治疗后免疫功能重建的影响研究[J].重庆医学,2023,52(18):2751-2757. [11] LI X L,DING H B,GENG W Q,et al.Predictive effects of body mass index on immune reconstitution among HIV-infected HAART users in China[J].BMC Infect Dis,2019,19(1):1-9. [12] MA Y,ZHANG F J,ZHAO Y,et al.Cohort profile:the Chinese national free antiretroviral treatment cohort[J].Int J Epidemiol,2010,39(4):973-979. [13] ZHAO Y,MCGOOGAN J M,WU Z Y.The benefits of immediate ART[J].J Int Assoc Provid AIDS Care,2019,18:1-4. [14] 吴虹,陈珺芳,许珂,等.2004—2020年杭州市艾滋病抗病毒治疗延迟的影响因素分析[J].预防医学,2021,33(12):1246-1248. [15] 张昕,张纪元,王福生.晚期AIDS病人HAART后免疫重建的研究进展[J].中国艾滋病性病,2016,22(4):299-304. [16] LIU J Y,WANG L F,HOU Y Y,et al.Immune restoration in HIV-1-infected patients after 12 years of antiretroviral therapy:a real-world observational study[J].Emerg Microbes Infect,2020,9(1):2550-2561. [17] 王思苑,孙丽琴,段司沁,等.CD4/CD8比值在HIV感染者中临床分析及其预测价值[J].新发传染病电子杂志,2019,4(2):91-96. [18] HOCQUELOUX L,AVETTAND-FENOEL V,JACQUOT S,et al.Long-term antiretroviral therapy initiated during primary HIV-1 infection is key to achieving both low HIV reservoirs and normal T cell counts[J].J Antimicrob Chemother,2013,68(5):1169-1178. [19] 俞海亮,杨跃诚,赵燕,等.德宏傣族景颇族自治州成年人HIV/AIDS抗病毒治疗后CD4+T淋巴细胞免疫重建及影响因素分析[J].中华流行病学杂志,2021,42(6):1050-1055. [20] SERRANO-VILLAR S,ZHOU Y,RODGERS A J,et al.Different impact of raltegravir versus efavirenz on CD4/CD8 ratio recovery in HIV-infected patients[J].J Antimicrob Chemother,2017,72(1):235-239. [21] 梅馨尹,王佳洁,劳晓洁,等.广西艾滋病患者免疫重建不良的预测模型建立[J].中国艾滋病性病,2021,27(12):1348-1352. [22] LINCOLN D,PETOUMENOS K,DORE G J.HIV/HBV and HIV/HCV coinfection,and outcomes following highly active antiretroviral therapy[J].HIV Med,2003,4(3):241-249. [23] SILVA C,PEDER L D,SILVA E S,et al.Impact of HBV and HCV coinfection on CD4 cells among HIV-infected patients:a longitudinal retrospective study[J].J Infect Dev Ctries,2018,12(11):1009-1018. [24] RALLON N I,LOPEZ M,SORIANO V,et al.Level,phenotype and activation status of CD4+FoxP3+regulatory T cells in patients chronically infected with human immunodeficiency virus and/or hepatitis C virus[J].Clin Exp Immunol,2009,155(1):35-43.