HIV感染者初始抗病毒治疗72周CD4/CD8变化及关联因素分析

Changes of CD4/CD8 ratio in HIV-infected patients undergoing initial antiretroviral therapy for 72 weeks and analysis of its influencing factors

  • 摘要:
    背景 及时有效的抗逆转录病毒治疗(antiretroviral therapy,ART)恢复HIV感染者受损的免疫功能是根本治疗措施,如何在早期精准评估患者免疫恢复状况是亟需探讨的临床问题。
    目的 分析HIV感染者初始抗病毒治疗72周CD4、CD8细胞及其比值的变化规律,探讨免疫重建的相关因素。
    方法 采集2011年1月 - 2018年12月在解放军总医院第五医学中心就诊入组并启动“2种核苷类逆转录酶抑制剂 + 1种非核苷类逆转录酶抑制剂”方案抗病毒治疗、服药依从性良好、长期随访的HIV感染者临床数据;观察CD4细胞与CD8细胞比值在ART不同时间节点的变化规律,并进行关联因素分析。
    结果 (1)研究设定时间内共1 796例HIV感染者入组,其中男性1 710例(95.21%)、女性86例(4.79%),平均(35.47 ± 11.68)岁。同性性传播占80.12%,异性性传播占13.31%。(2)ART前CD4细胞(/μL)、CD8细胞(/μL)分别为264 ± 166、935 ± 473;CD4/CD8比值为0.28 ± 0.18,82.79%的感染者比值低于0.5。替诺福韦、拉米夫定、依非韦伦三联抗病毒治疗24周、48周、72周后,CD4细胞(/μL)分别升至374 ± 187、589 ± 207、726 ± 377,CD8细胞(/μL)分别降至779 ± 350、734 ± 284、708 ± 299,CD4/CD8比值分别升至0.55 ± 0.33、0.84 ± 0.20、1.03 ± 0.38;与基线水平相比,三个指标的差异均有统计学意义(P<0.05)。但ART 48周之后,各指标增幅均明显放缓。(3)多因素分析显示,基线CD4低(<200/μL)、基线CD8高(≥800/μL)和基线CD4/CD8比值低(<0.5)者抗病毒治疗72周CD4/CD8比值恢复更差(P<0.05,OR>1)。
    结论 HIV感染者开始ART前CD4细胞水平普遍较低、CD4/CD8比值倒置严重,ART 72周后多数HIV感染者CD4细胞得以恢复,CD4/CD8比值明显改善,但仍有部分感染者免疫重建不良。基线CD4、CD8水平以及CD4/CD8比值是影响感染者免疫恢复的重要关联因素。

     

    Abstract:
    Background Restoring the impaired immune function of infected people through timely and effective antiretroviral therapy (ART) is the current fundamental treatment measure. How to accurately evaluate the immune recovery of patients early is an urgent clinical problem to be discussed.
    Objective  To investigate the changes of CD4 and CD8 cells and their ratio in HIV-infected patients who accept initial antiviral treatment (ART) for 72 weeks, and explore the relevant influencing factors of immune reconstitution.
    Methods  The real-world data of the HIV infected patients from January 2011 to December 2018, who received antiretroviral therapy (ART) with “2NRTs + NNRTIs” regimen during that period in our medical center, were collected; and the changes of CD4/ CD8 at different time points of ART were observed. These data were used for analyses of contributing factors.
    Results A total of 1 796 HIV-infected patients were enrolled, including 1 710 males (95.21%) and 86 females (4.79%), who were (35.47 ± 11.68) years old on average. In terms of the transmission route, homosexual sexual transmission (MSM) accounted for 80.12%, and heterosexual transmission accounted for 13.31%. The CD4 and CD8 cells before ART was (264 ± 166)/μL and (935 ± 473)/μL respectively, and the CD4/CD8 ratio was 0.28 ± 0.18, with 82.79% of infected patients being less than 0.5. After 24 weeks, 48 weeks, and 72 weeks of ART with tenofovir, lamivudine, and eafavirenz, the patients’ CD4 cells rose to (374 ± 187)/μL, (589 ± 207)/μL, (726 ± 377)/μL, respectively, and CD8 cells fell to (779 ± 350)/μL, (734 ± 284)/μL, (708 ± 299)/μL, respectively. Meanwhile, the CD4/CD8 ratio rose to 0.55 ± 0.33, 0.84 ± 0.20, 1.03 ± 0.38, respectively. The differences were statistically significant compared to baseline levels (all P <0.05). However, after 48 weeks, the growth rate of all indicators was significantly slower, and the difference was not statistically significant when comparing CD4 cells of 72 weeks with those of 48 weeks (P>0.05). Multivariate analysis showed that higher baseline CD8 level, lower baseline CD4 level and CD4/CD8 ratio, were closely related to longer recovery of CD4/CD8 ratio at 72 weeks' antiviral therapy.
    Conclusion  The CD4 cell count and CD4/CD8 ratio of the HIV-infected patients are generally low before ART. After 72 weeks of ART, the CD4 cells of most patients are recovered and CD4/CD8 ratio improves significantly, but some patients still show poor immune reconstruction. Baseline CD4, CD8 levels and CD4/CD8 ratio are important associated-factors affecting the immune recovery of the HIV-infected patients with ART.

     

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