CD4/CD8比值在HIV感染者中临床分析及其预测价值
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摘要
目的在抗逆转录病毒治疗(ART)前HIV感染者中,分析不同的CD4/CD8比值与临床特征相互关系,探讨其预测临床意义的价值。方法回顾性收集1982年1月至2018年10月由深圳市第三人民医院长期门诊随访艾滋病患者11 357人,因资料不全剔除835人,实际纳入研究对象10 522人。按不同CD4/CD8比值分成3组,即CD4/CD8比值<0.2(3535人),0.2≤CD4/CD8比值<0.4(4410人),CD4/CD8比值≥0.4(2577人)。回顾性分析不同研究组基本人口学资料、临床特征、CD4~+T淋巴细胞、CD8~+T淋巴细胞及HIV病毒载量。结果在10522个研究对象中,平均年龄(33.64±10.34)岁,CD4~+T淋巴细胞绝对值为(246.96±160.26)个/μl,CD8~+T淋巴细胞绝对值为(898.69±523.28)个/μl,CD4/CD8比值为0.30±0.24。在三个CD4/CD8比值研究组中,通过多元线性回归分析发现,CD4/CD8比值水平与性别(t值4.135,95%CI:0.017～0.046)、机会感染(t值-21.609,95%CI:-0.103～-0.086)、WHO临床分期(t值-38.782,95%CI:-0.092～-0.083)、确诊HIV后延迟ART时间(t值-2.904,95%CI:-0.022～-0.004)、HIVRNA载量(t值-16.385,95%CI:-0.047～-0.037)有密切相关性,具有统计学差异,P均<0.01;而与年龄(t值-1.006,95%CI:-0.001～0.000)、体重指数(t值-1.161,95%CI:-0.002～0.001)、死亡人数(t值0.058,95%CI:-0.044～0.047)无明显相关性,P均>0.05。结论 ART前HIV感染者CD4/CD8比值水平越低,提示HIV感染者合并机会感染可能性越大、确认HIV后延迟ART时间越长、WHO临床分期越晚、HIVRNA载量越高。但是,CD4/CD8比值水平与ART前HIV感染者年龄、死亡结局无明显相关性。这提示CD4/CD8比值可能作为HIV感染者合并机会感染临床情况评估,具有一定预测价值。
Objcetive To investigate the role of CD4/CD8 ratio in predicting clinical outcomes in Human Immunodeficiency Virus(HIV) infected Patients with newly antiretroviral treatment(ART).Method Total of 11357 HIV infected patients with newly ART admitted during January 1982 to October2018 in Shenzhen the Third People's Hospital were analyzed, retrospectively. 10,522 subjects were included in the study due to exclusion of subjects with incomplete information. The clinical characteristics and levels of CD4/CD8 ratio were collected. According to the tertiles of CD4/CD8 ratio [0–0.20, 0.20–0.40(reference), >0.40], the patients were divided into three groups: CD4/CD8 ratio <0.2 group(3535 cases), 0.2≤CD4/CD8 ratio <0.4 group(4410 cases)and CD4/CD8 rati≥0.4 group(2577 cases). Results Of the 10522 subjects, mean age ± Standard Deviation(SD) was(33.64 ±10.34) years,mean CD4+T-cells ± SD was(246.96±160.26)cells/mm~3,mean CD8+T-cells ± SD was(898.69± 523.28) cells/mm~3 and mean CD4/CD8 ratio ± SD was(0.30 ± 0.24). Based on multivariate linear regression analysis, factors associated with the CD4/CD8 ratio were gender,(t-tests 4.135, 95%CI : 0.017～0.046, P <0.001),opportunistic infections(t-tests-21.609, 95% CI :-0.103～-0.086, P<0.001), clinical stages of HIV infection with the WHO classification(t-tests-38.782, 95% CI:-0.092～-0.083, P<0.001),time between HIV diagnosis and ART initiation(t-tests-2.904, 95% CI:-0.022～-0.004, P<0.001) and HIVRNA loads(t-tests-16.385, 95% CI:-0.047～-0.037, P<0.001).The CD4/CD8 ratio in multivariate analysis was not associated with age(t-tests-1.006, 95% CI:-0.001～-0.000, >0.05), body mass index(t-tests-1.161, 95%CI:-0.002～-0.001, >0.05), and deaths(t-value 0.058, 95% CI:-0.044-0.047, >0.05). Conclusions In this large cohort collaboration, the lower CD4/CD8 ratio in HIV-infected patients with newly ART was associatde with the longer time between HIV diagnosis and ART initiation,the later clinical stages of HIV infection with the WHO classification and the higher HIVRNA loads,which indicated that more opportunistic infections.This large study showed the use of CD4/CD8 ratio can be used as a prognostic marker for clinical progression of opportunistic infections.
Objcetive To investigate the role of CD4/CD8 ratio in predicting clinical outcomes in Human Immunodeficiency Virus(HIV) infected Patients with newly antiretroviral treatment(ART).Method Total of 11357 HIV infected patients with newly ART admitted during January 1982 to October2018 in Shenzhen the Third People's Hospital were analyzed, retrospectively. 10,522 subjects were included in the study due to exclusion of subjects with incomplete information. The clinical characteristics and levels of CD4/CD8 ratio were collected. According to the tertiles of CD4/CD8 ratio [0–0.20, 0.20–0.40(reference), >0.40], the patients were divided into three groups: CD4/CD8 ratio <0.2 group(3535 cases), 0.2≤CD4/CD8 ratio <0.4 group(4410 cases)and CD4/CD8 rati≥0.4 group(2577 cases). Results Of the 10522 subjects, mean age ± Standard Deviation(SD) was(33.64 ±10.34) years,mean CD4+T-cells ± SD was(246.96±160.26)cells/mm~3,mean CD8+T-cells ± SD was(898.69± 523.28) cells/mm~3 and mean CD4/CD8 ratio ± SD was(0.30 ± 0.24). Based on multivariate linear regression analysis, factors associated with the CD4/CD8 ratio were gender,(t-tests 4.135, 95%CI : 0.017～0.046, P <0.001),opportunistic infections(t-tests-21.609, 95% CI :-0.103～-0.086, P<0.001), clinical stages of HIV infection with the WHO classification(t-tests-38.782, 95% CI:-0.092～-0.083, P<0.001),time between HIV diagnosis and ART initiation(t-tests-2.904, 95% CI:-0.022～-0.004, P<0.001) and HIVRNA loads(t-tests-16.385, 95% CI:-0.047～-0.037, P<0.001).The CD4/CD8 ratio in multivariate analysis was not associated with age(t-tests-1.006, 95% CI:-0.001～-0.000, >0.05), body mass index(t-tests-1.161, 95%CI:-0.002～-0.001, >0.05), and deaths(t-value 0.058, 95% CI:-0.044-0.047, >0.05). Conclusions In this large cohort collaboration, the lower CD4/CD8 ratio in HIV-infected patients with newly ART was associatde with the longer time between HIV diagnosis and ART initiation,the later clinical stages of HIV infection with the WHO classification and the higher HIVRNA loads,which indicated that more opportunistic infections.This large study showed the use of CD4/CD8 ratio can be used as a prognostic marker for clinical progression of opportunistic infections.
引文
[1]Hulgan T,Shepherd BE,Raffanti SP,et al.Absolute count and percentage of CD4+lymphocytes are independent predictors of disease progression in HIVinfected persons initiating highly active antiretroviral therapy[J].JInfect Dis,2007,195:425-431.
[2]Hulgan T,Raffanti S,Kheshti A,et al.CD4 lymphocyte percentage predicts disease progression in HIV-infected patients initiating highly active antiretroviral therapy with CD4 lymphocyte counts>350 lymphocytes/mm3[J].JInfect Dis,2005,192:950-957.
[3]Young J,Psichogiou M,Meyer L,et al.CD4 Cell Count and the Risk of AIDS or Death in HIV-Infected Adults on Combination Antiretroviral Therapy with a Suppressed Viral Load:A Longitudinal Cohort Study from COHERE[J].PLoS Medicine,2012,9(3):e1001194.
[4]Wikby A,M?nsson IA,Johansson B,et al.The immune-risk profile is associated with age and gender:findings from three Swedish population studies of individuals 20-100years of age[J].Biogerontology,2008,9:299-308.
[5]Petoumenos K,Choi JY,Hoy J,et al.CD4:CD8 ratio comparison between cohorts of HIV-positive Asians and Caucasians upon commencement of antiretroviral therapy[J].Antivir Ther,2017,22(8):659-668.
[6]Mussini C,Lorenzini P,Cozzi-Lepri A,et al.CD4/CD8 ratio normalisation and non-AIDS-related events in individuals with HIV who achieve viral load suppression with antiretroviral therapy:an observational cohort study[J].Lancet HIV,2015,2(3):e98-106.
[7]Han WM,Apornpong T,Kerr SJ,et al,CD4/CD8 ratio normalization rates and low ratio as prognostic marker for non-AIDS defining events among long-term virologically suppressed people living with HIV[J].AIDSResearch and Therapy,2018,15(1):13.
[8]中华医学会感染学分会艾滋病丙型肝炎学组.艾滋病诊疗指南2018年版[J].新发传染病电子杂志,2019,4(2):65-84.
[9]Wikby A,M?nsson IA,Johansson B,et al.The immune-risk profile is associated with age and gender:findings from three Swedish population studies of individuals 20-100years of age[J].Biogerontology,2008,9:299-308.
[10]Appay V,Sauce D.Immune activation and inflammation in HIV-1 infection:causes and consequences[J].J Pathol,2008,214(2):231-241.
[11]Serrano-Villar S,Moreno S,Fuentes-Ferrer M,et al.The CD4:CD8 ratio is associated with markers of ageassociated disease in virally suppressed HIV-infected patients with immunological recovery[J].HIV Med,2014,15(1):40-49.
[12]Margolick JB,Munoz A,Donnenberg AD,et al.Failure of T-cell homeostasis preceding AIDS in HIV-1 infection.The Multicenter AIDS Cohort Study[J].Nat Med 1,1995,1(7):674-680.
[13]Lu W,Mehrajv,Vuhohk,et al.CD4:CD8ratioas frontier marker for clinical outcone,immudeysfunction and viral reser-voirsize in virologically suppressed HIV-positive parients[J].JintAIDS Soc,2015,18:20053.
[14]Johnston J,Parsons R,Botelho F,et al.T-Cell Phenotypes Predictive of Frailty and Mortality in Elderly Nursing Home Reisdents[J].J Am Geriatr Soc,2017,65(1):153-159.
[15]Serrano-Villar S,Deeks S.CD4/CD8 ratio:an emerging biomarker for HIV[J].Lancet HIV,2015,2(3):76-77.
[16]Trickey A,May MT,Schommers P,et al.CD4:CD8 Ratio and CD8 Count as Prognostic Markers for Mortality in Human Immunodeficiency Virus-Infected Patients on Antiretroviral Therapy:The Antiretroviral Therapy Cohort Collaboration(ART-CC)[J].Clinical Infectious Diseases,2017,65(6):959-966.
[2]Hulgan T,Raffanti S,Kheshti A,et al.CD4 lymphocyte percentage predicts disease progression in HIV-infected patients initiating highly active antiretroviral therapy with CD4 lymphocyte counts>350 lymphocytes/mm3[J].JInfect Dis,2005,192:950-957.
[3]Young J,Psichogiou M,Meyer L,et al.CD4 Cell Count and the Risk of AIDS or Death in HIV-Infected Adults on Combination Antiretroviral Therapy with a Suppressed Viral Load:A Longitudinal Cohort Study from COHERE[J].PLoS Medicine,2012,9(3):e1001194.
[4]Wikby A,M?nsson IA,Johansson B,et al.The immune-risk profile is associated with age and gender:findings from three Swedish population studies of individuals 20-100years of age[J].Biogerontology,2008,9:299-308.
[5]Petoumenos K,Choi JY,Hoy J,et al.CD4:CD8 ratio comparison between cohorts of HIV-positive Asians and Caucasians upon commencement of antiretroviral therapy[J].Antivir Ther,2017,22(8):659-668.
[6]Mussini C,Lorenzini P,Cozzi-Lepri A,et al.CD4/CD8 ratio normalisation and non-AIDS-related events in individuals with HIV who achieve viral load suppression with antiretroviral therapy:an observational cohort study[J].Lancet HIV,2015,2(3):e98-106.
[7]Han WM,Apornpong T,Kerr SJ,et al,CD4/CD8 ratio normalization rates and low ratio as prognostic marker for non-AIDS defining events among long-term virologically suppressed people living with HIV[J].AIDSResearch and Therapy,2018,15(1):13.
[8]中华医学会感染学分会艾滋病丙型肝炎学组.艾滋病诊疗指南2018年版[J].新发传染病电子杂志,2019,4(2):65-84.
[9]Wikby A,M?nsson IA,Johansson B,et al.The immune-risk profile is associated with age and gender:findings from three Swedish population studies of individuals 20-100years of age[J].Biogerontology,2008,9:299-308.
[10]Appay V,Sauce D.Immune activation and inflammation in HIV-1 infection:causes and consequences[J].J Pathol,2008,214(2):231-241.
[11]Serrano-Villar S,Moreno S,Fuentes-Ferrer M,et al.The CD4:CD8 ratio is associated with markers of ageassociated disease in virally suppressed HIV-infected patients with immunological recovery[J].HIV Med,2014,15(1):40-49.
[12]Margolick JB,Munoz A,Donnenberg AD,et al.Failure of T-cell homeostasis preceding AIDS in HIV-1 infection.The Multicenter AIDS Cohort Study[J].Nat Med 1,1995,1(7):674-680.
[13]Lu W,Mehrajv,Vuhohk,et al.CD4:CD8ratioas frontier marker for clinical outcone,immudeysfunction and viral reser-voirsize in virologically suppressed HIV-positive parients[J].JintAIDS Soc,2015,18:20053.
[14]Johnston J,Parsons R,Botelho F,et al.T-Cell Phenotypes Predictive of Frailty and Mortality in Elderly Nursing Home Reisdents[J].J Am Geriatr Soc,2017,65(1):153-159.
[15]Serrano-Villar S,Deeks S.CD4/CD8 ratio:an emerging biomarker for HIV[J].Lancet HIV,2015,2(3):76-77.
[16]Trickey A,May MT,Schommers P,et al.CD4:CD8 Ratio and CD8 Count as Prognostic Markers for Mortality in Human Immunodeficiency Virus-Infected Patients on Antiretroviral Therapy:The Antiretroviral Therapy Cohort Collaboration(ART-CC)[J].Clinical Infectious Diseases,2017,65(6):959-966.