Survival analysis and influencing factors of AIDS patients treated with antiretroviral therapy in Lanzhou from 2005 to 2023
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摘要:
目的 了解2005―2023年兰州市艾滋病(acquired immunodeficiency syndrome, AIDS)患者抗病毒治疗后的生存状况、治疗效果及影响因素。 方法 采用回顾性队列研究方法，收集2005―2023年兰州市接受抗病毒治疗的2 766例患者信息，应用寿命表法计算研究对象的死亡概率、生存概率和累积生存率; 利用Kaplan-Meier法计算研究对象截止观察终点的平均生存时间，并采用Log-rank法检验其差异有无统计学意义。采用Cox比例风险回归模型进行单因素与多因素分析。构建列线图模型，预测抗病毒治疗预后。 结果 患者平均确诊年龄为(38.14±13.01)岁，中位随访时间为63(31, 93)月，第1、3、5、10年的累积生存率分别为98.46%、97.44%、96.99%、95.86%，总病死率为1.27/100人年，AIDS相关病死率为0.57/100人年，多因素Cox比例风险回归模型分析结果显示，基线CD4+T淋巴细胞(简称CD4)计数、最近病毒载量检测值、目前WHO临床分期是研究对象生存时间的影响因素(均P＜0.05)，其中基线CD4计数≥400个/μL组(HR=0.443, 95% CI: 0.291~0.673, P＜0.001)死亡风险较低，最近病毒载量检测值≥1 000 copies/mL组(HR=12.725, 95% CI: 6.548~24.729, P＜0.001)、WHO临床分期Ⅳ期组(HR=3.517, 95% CI: 1.785~6.932, P＜0.001)死亡风险较高。纳入上述3个影响因素构建列线图模型，模型区分度C-index=0.892(95% CI: 0.847~0.934)，表明模型有良好的预测能力。 结论 2005―2023年兰州市AIDS患者抗病毒治疗效果较好，患者生存率和病毒学抑制率较高。疾病初期进行规范治疗是降低患者死亡风险、提高生存率的关键举措。 Abstract:Objective To investigate the survival status, treatment effect, and influencing factors of acquired immunodeficiency syndrome (AIDS) patients after antiretroviral therapy in Lanzhou from 2005 to 2023. Methods A retrospective cohort study was conducted to collect information on 2 766 patients who received antiretroviral therapy in Lanzhou from 2005 to 2023. The life table method was used to calculate the mortality probability, survival probability, and cumulative survival rate of the subjects. The Kaplan-Meier method was applied to calculate the average survival time of the subjects up to the end of observation, with the Log-rank test used to determine the statistical significance of the differences. Cox proportional hazard regression models were used for both univariate and multivariate analyses. Construction of a nomogram model was used to predict prognosis of antiretroviral therapy. Results The average age at diagnosis was (38.14±13.01) years, and the median follow-up time was 63 (31, 93) months. The cumulative survival rates at 1, 3, 5, and 10 years were 98.46%, 97.44%, 96.99%, and 95.86%, respectively. The total mortality rate was 1.27 per 100 person-years, and the AIDS-related mortality rate was 0.57 per 100 person-years. Multivariate Cox regression analysis revealed that baseline CD4 cell count, the most recent viral load test result, and current WHO clinical stage were significant factors influencing the survival time of the subjects, with statistical significance (P < 0.05). Specifically, the group with baseline CD4 ≥ 400/μL (HR=0.443, 95% CI: 0.291-0.673, P < 0.001) had a lower risk of death, while the group with a recent viral load test result ≥ 1 000 copies/mL (HR=12.725, 95% CI: 6.548-24.729, P < 0.001) and the WHO clinical stage Ⅳ group (HR=3.517, 95% CI: 1.785-6.932, P < 0.001) had a higher risk of death. Incorporating the above three influencing factors to construct a nomogram model, the model differentiation C-index=0.892 (95% CI: 0.847-0.934), and the model possessed good predictive ability. Conclusions The antiretroviral therapy for HIV/AIDS in Lanzhou has achieved significant results, with high patient survival rates and virological suppression rates. Standardized treatment in the early stage of the disease is a crucial measure to reduce the risk of death and improve survival rates. -
图 1 兰州市接受抗病毒治疗患者艾滋病相关死亡列线图
Figure 1. Nomogram of AIDS-related deaths among patients receiving antiretroviral therapy in Lanzhou City
表 1 抗病毒治疗患者生存分析要素与赋值
Table 1. Survival analysis elements and assignments for patients on antiretroviral therapy
生存分析要素Elements of survival analysis 定义/赋值Definition/assignment 观察起点Starting point for observation 研究对象首次抗病毒治疗的时间(2005―2023年)
Time to first antiretroviral therapy for study participants (2005-2023)终点事件Terminal event 研究对象死于艾滋病相关疾病Study subjects died of AIDS-related illnesses 删失事件Deletion event 研究对象停药、失访、非艾滋病死亡、至观察终点仍然存活
Study subjects discontinued, missed visits, non-AIDS deaths, survived to observation endpoints生存时间/月Survival time/months 研究对象开始抗病毒治疗到死亡或者删失的时间
Time from initiation of antiretroviral therapy to death or censoring of study subjects生存结局Survival ending 1、3、4 =删失事件，2 =终点事件1, 3, 4 = deletion event, 2 = terminal event 
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表 2 兰州市2 766例抗病毒治疗患者基本情况及分组生存曲线Log-rank检验
Table 2. Basic information of 2 766 patients on antiretroviral therapy in Lanzhou City and Log-rank test for subgroup survival curves
变量Variable 人数
Number of people①
(n＝2 766)平均生存时间/月
Average survival time/month (95% CI)Kaplan-Meier法
Kaplan-Meier methodLog-rank χ2值value P值
value性别Gender 0.546 0.460 男性Male 2 511(90.78) 191.980(189.333~194.628) 女性Female 255(9.22) 202.710(198.521~206.899) 确诊年龄/岁Age of diagnosis/years 16.266 ＜0.001 0~＜30 865(31.27) 201.604(196.908~206.300) 30~＜60 1 707(61.71) 191.974(189.190~194.757) ≥60 194(7.01) 165.192(157.391~172.993) 婚姻状况Marital status 0.269 0.604 已婚或有配偶Married or with a spouse 1 308(47.29) 191.807(188.428~195.187) 未婚、离异或丧偶Not married, divorced or widowed 1 458(52.71) 199.859(196.557~203.160) 感染途径Route of infection 15.261 0.002 同性性传播Homosexual transmission 1 351(48.84) 185.784(183.337~188.231) 异性性传播Heterosexual transmission 947(34.24) 183.863(179.640~188.086) 注射毒品Drug injection 50(1.81) 185.315(170.276~200.353) 血液/母婴/其他传播Blood/mother-to-child/other transmission 418(15.11) 193.511(186.980~200.043) 基线CD4+T淋巴细胞计数/(个·μL-1)) Baseline CD4 cell count/(cells·μL-1) 269.021 ＜0.001 0~＜200 1 094(39.55) 194.927(190.673~199.181) 200~＜400 1 036(37.45) 185.959(184.019~187.899) ≥400 567(20.50) 145.626(144.425~146.827) 不详Unspecified 69(2.49) 38.254(25.238~51.270) 最近病毒载量检测值Most recent viral load test value/(copies·mL-1) 610.593 ＜0.001 ＜1 000 2 326(84.09) 204.302(202.320~206.284) ≥1 000 242(8.75) 137.467(123.806~151.128) 不详Unspecified 198(7.16) 50.979(41.728~60.229) 是否出现症状、体征或疾病Presence of signs, symptoms or disease 3.951 0.047 否No 2 564(92.70) 179.373(177.410~181.336) 是Yes 202(7.30) 193.838(186.378~201.297) 是否接受复方新诺明预防感染Received cotrimoxazole to prevent infection 9.455 0.002 否No 2 363(85.43) 200.387(197.751~203.023) 是Yes 403(14.57) 179.799(174.390~185.208) 从确诊到初治的时间间隔Interval from diagnosis to first treatment/d 0.711 0.701 0~＜30 1 332(48.16) 194.360(191.963~196.757) 30~＜90 758(27.40) 189.428(184.893~193.964) ≥90 676(24.44) 198.303(193.594~203.012) 病人来源Source of the patient 0.049 0.825 本地治疗Local treatment 2 561(92.59) 198.840(196.201~201.479) 转入治疗Transfer to treatment 205(7.41) 187.187(182.603~191.772) 目前WHO临床分期Current WHO clinical staging 55.163 ＜0.001 Ⅰ期Stage Ⅰ 1 677(60.63) 183.050(181.471~184.628) Ⅱ期Stage Ⅱ 116(4.19) 167.941(159.052~176.831) Ⅲ期Stage Ⅲ 87(3.15) 184.563(175.164~193.961) Ⅳ期Stage Ⅳ 886(32.03) 191.224(186.107~196.341) 初始治疗方案Initial treatment options 0.812 0.368 一线治疗方案First-line treatment options 2 635(95.26) 198.946(196.422~201.470) 二线治疗方案Second-line treatment options 131(4.74) 115.000(105.493~124.507) 注：①以人数(占比/%)表示。
Note: ① Number of people (proportion/%).
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表 3 2005―2023年兰州市接受抗病毒治疗患者的生存率表
Table 3. Survival tables for patients receiving antiretroviral therapy in Lanzhou City, 2005-2023
生存时间/月
Survival time/month期间观察例数
The number of cases observed during the period删失例数
Deletion numbers有效观察例数
Number of effective observers死亡例数
Dead numbers死亡概率
Probability of death/%生存概率
Probability of survival/%累积生存率
Cumulative survival rate/%累积生存率标准误
Standard error of cumulative survival rate0~＜12 2 766 328 2 602.0 40 1.54 98.46 98.46 0.002 12~＜24 2 398 151 2 322.5 12 0.52 99.48 97.95 0.003 24~＜36 2 235 273 2 098.5 11 0.52 99.48 97.44 0.003 36~＜48 1 951 211 1 845.5 5 0.27 99.73 97.18 0.003 48~＜60 1 735 275 1 597.5 3 0.19 99.81 96.99 0.004 60~＜72 1 457 269 1 322.5 5 0.38 99.62 96.63 0.004 72~＜84 1 183 277 1 044.5 3 0.29 99.71 96.35 0.004 84~＜96 903 254 776.0 0 0.00 100.00 96.35 0.004 96~＜108 649 262 518.0 1 0.19 99.81 96.16 0.005 108~＜120 386 137 317.5 1 0.32 99.69 95.86 0.005 120~＜132 248 68 214.0 2 0.93 99.07 94.97 0.008 132~＜144 178 64 146.0 0 0.00 100.00 94.97 0.008 144~＜156 114 44 92.0 2 2.17 97.83 92.90 0.017 156~＜168 68 35 50.5 0 0 100.00 92.90 0.017 168~＜180 33 15 25.5 0 0 100.00 92.90 0.017 180~＜192 18 14 11.0 0 0 100.00 92.90 0.017 192~＜204 4 3 2.5 0 0 100.00 92.90 0.017 204~216 1 1 0.5 0 0 100.00 92.90 0.017 注：①以人数(占比/%)表示。
Note: ① Number of people (proportion/%).
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表 4 兰州市2 766名艾滋病患者抗病毒治疗后生存时间的单因素和多因素Cox回归
Table 4. Univariate and multifactorial Cox analysis of survival time after antiretroviral therapy in 2 766 acquired immunodeficiency syndrome patients in Lanzhou City
变量Variable 单因素Cox回归
Univariate Cox analysis多因素Cox回归
Multifactorial Cox analysisWald χ2值value P值
valueHR值value
(95% CI)Wald χ2值value P值
valueHR值value
(95% CI)性别Gender 0.537 0.464 男性Male 1.000 女性Female 0.537 0.464 0.733(0.320~1.682) 确诊年龄/岁Age of diagnosis/years 14.724 0.001 3.025 0.220 0~＜30 1.000 1.000 30~＜60 5.806 0.016 2.010(1.139~3.546) 0.985 0.321 1.346(0.749~2.419) ≥60 14.695 ＜0.001 4.433(2.070~9.493) 3.023 0.082 2.017(0.915~4.449) 婚姻状况Marital status 0.266 0.606 已婚或有配偶Married or with a spouse 1.000 未婚、离异或丧偶Not married, divorced or widowed 0.266 0.606 0.894(0.584~1.368) 感染途径Route of infection 14.191 0.003 1.873 0.599 同性性传播Homosexual transmission 1.000 1.000 异性性传播Heterosexual transmission 4.627 0.031 1.765(1.052~2.961) 1.853 0.173 1.453(0.849~2.486) 注射毒品Drug injection 3.792 0.052 3.279(0.992~10.835) 0.056 0.813 1.160(0.339~3.972) 血液/母婴/其他传播Blood/mother-to-child/other transmission 12.753 ＜0.001 2.757(1.580~4.809) 0.335 0.562 1.191(0.660~2.148) 基线CD4+T淋巴细胞计数/(个·μL-1) Baseline CD4 cell count/(cells·μL-1) 126.372 ＜0.001 19.402 ＜0.001 0~＜200 1.000 1.000 200~＜400 19.580 ＜0.001 0.241(0.128~0.453) 9.426 0.002 0.503(0.324~0.780) ≥400 11.283 0.001 0.206(0.082~0.518) 14.524 ＜0.001 0.443(0.291~0.673) 不详Unspecified 70.047 ＜0.001 11.600(6.534~20.593) 7.588 0.006 2.477(1.299~4.724) 最近病毒载量检测值Most recent viral load test value/(copies·mL-1) 230.996 ＜0.001 160.278 ＜0.001 ＜1 000 1.000 1.000 ≥1 000 61.794 ＜0.001 13.934(7.225~26.874) 56.298 ＜0.001 12.725(6.548~24.729) 不详Unspecified 230.994 ＜0.001 82.714(46.805~146.173) 157.650 ＜0.001 57.801(30.683~108.887) 是否出现症状、体征或疾病Presence of signs, symptoms or disease 3.816 0.051 否No 1.000 是Yes 3.816 0.051 1.830(0.998~3.354) 是否接受复方新诺明预防感染Received cotrimoxazole to prevent infection 8.986 0.003 0.047 0.829 否No 1.000 是Yes 8.986 0.003 2.067(1.286~3.324) 0.047 0.829 0.945(0.567~1.575) 从确诊到初治的时间间隔Interval from diagnosis to first treatment/d 0.703 0.704 0~＜30 1.000 30~＜90 0.614 0.433 1.223(0.739~2.023) ≥90 0.359 0.549 1.175(0.693~1.993) 患者来源Source of the patient 0.048 0.826 本地治疗Local treatment 1.000 转入治疗Transfer to treatment 0.048 0.826 0.911(0.397~2.090) 目前WHO临床分期Current WHO clinical staging 43.898 ＜0.001 13.727 0.003 Ⅰ期Stage Ⅰ 1.000 1.000 Ⅱ期Stage Ⅱ 2.969 0.085 2.574(0.878~7.543) 3.990 0.046 3.163(1.022~9.791) Ⅲ期Stage Ⅲ 2.280 0.131 2.552(0.756~8.607) 1.578 0.209 2.225(0.639~7.747) Ⅳ期Stage Ⅳ 43.196 ＜0.001 5.504(3.310~9.153) 13.200 ＜0.001 3.517(1.785~6.932) 初始治疗方案Initial treatment options 0.753 0.386 一线治疗方案First-line treatment options 1.000 二线治疗方案Second-line treatment options 0.753 0.386 0.417(0.058~3.010)
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