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首页> 外文期刊>American Journal of Epidemiology >Determining the Effect of Highly Active Antiretroviral Therapy on Changes in Human Immunodeficiency Virus Type 1 RNA Viral Load using a Marginal Structural Left-censored Mean Model
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Determining the Effect of Highly Active Antiretroviral Therapy on Changes in Human Immunodeficiency Virus Type 1 RNA Viral Load using a Marginal Structural Left-censored Mean Model

机译:使用边缘结构左删减均值模型确定高活性抗逆转录病毒疗法对人类免疫缺陷病毒1型RNA病毒载量变化的影响

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摘要

Highly active antiretroviral therapy (HAART) dramatically reduces the load of circulating human immunodeficiency virus type 1 (HIV-1) by blocking replication at multiple points in the viral life cycle, but the long-term effect of HAART on viral load remains unclear. In the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study, 918 HIV-1-infected men and women who were not using antiretroviral therapy were followed for a median of 5.8 years between 1996 and 2005. Follow-up yielded 3,629 person-years of observation, during which 286 (31%) of the participants initiated HAART. A marginal structural left-censored linear model for semiannual repeated assessments of viral load showed a 1.9 log10 decrease in viral load after HAART initiation as compared with nonuse (95% confidence interval: 1.7, 2.2), which remained stable over the course of follow-up but was stronger among men (interaction p < 0.001). This association was attenuated by 10% when the authors ignored the left-censoring of viral load measurements (which comprised 20% of measurements (1,420/7,258)) and attenuated by 57% when the authors adjusted for time-varying covariates in a standard fashion rather than using the marginal structural model. In conclusion, the clinically important protective effect of HAART on dampening viral load appears to be rapid, present at CD4 cell counts greater than 350 cells/mm3, and sustained beyond 6 years.
机译:高活性抗逆转录病毒疗法(HAART)通过阻止病毒生命周期中多个点的复制来显着降低循环型1型人类免疫缺陷病毒(HIV-1)的负荷,但是HAART对病毒负荷的长期影响仍不清楚。在“多中心艾滋病队列研究”和“妇女机构间艾滋病毒研究”中,对1996年至2005年间918名未使用抗逆转录病毒疗法的HIV-1感染的男性和女性进行了5.8年的中位随访。随访发现,该病的发生率为3,629人年。观察,其中286(31%)位参与者发起了HAART。半年一次重复评估病毒载量的边缘结构左删失线性模型显示,与未使用相比,HAART启动后病毒载量减少了1.9 log 10 (95%置信区间:1.7、2.2),在随访过程中保持稳定,但在男性中更强(相互作用p <0.001)。当作者忽略病毒载量测量的左删减(包括20%的测量值(1,420 / 7,258))时,这种关联会衰减10%;而当作者以标准方式调整时变协变量时,这种关联会衰减57%。而不是使用边际结构模型。总之,HAART对减轻病毒载量的临床重要保护作用似乎是迅速的,在CD4细胞数大于350细胞/ mm 3 时存在,并可持续超过6年。

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  • 来源
    《American Journal of Epidemiology》 |2007年第2期|219-227|共9页
  • 作者单位

    Department of Epidemiology Bloomberg School of Public Health Johns Hopkins University Baltimore MD;

    Department of Epidemiology School of Public Health Harvard University Boston MA;

    Montefiore Medical Center Bronx NY;

    Department of Medicine David Geffen School of Medicine University of California Los Angeles Los Angeles CA;

    Department of Biostatistics School of Public Health Harvard University Boston MA;

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