Viremia Copy-Years Predicts Mortality Among Treatment-Naive HIV-Infected Patients Initiating Antiretroviral Therapy
Viremia Copy-Years Predicts Mortality Among Treatment-Naive HIV-Infected Patients Initiating Antiretroviral Therapy
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DOI：
10.1093/cid/cir526
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发表时间：
2011-11-01
影响因子：
11.8
通讯作者：
Saag, Michael S.
中科院分区：
文献类型：
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作者：
Mugavero, Michael J.;Napravnik, Sonia;Saag, Michael S.
背景资料。横截面血浆人类免疫缺陷病毒(HIV)病毒载量(VL)测量已被证明对临床和研究目的具有极高的价值。然而，横断面VL措施不能纵向捕捉累积的血浆HIV负荷。我们评估了在联合抗逆转录病毒治疗(ART)开始后，暴露于HIV复制对死亡率的累积影响。我们从2000年到2008年在8个艾滋病研究中心综合临床系统网站纳入了接受ART治疗的未接受治疗的HIV感染者。使用VL曲线下的面积为每个患者确定病毒血症复制年，这是累积血浆HIV暴露的一个随时间变化的衡量标准。多变量COX模型用于评估病毒血症复制年限与全因死亡率的独立关联性。获得6579人年随访的2027例患者中，病毒血症复制年数的中位数为5.3log(10)Copy/mL(四分位数范围为4.9~6.3)，死亡85例(4.2%)。当单独评估时，病毒血症复制年(危险比[HR]=1.81每对数(10)拷贝Xy/毫升；95%可信区间[CI]，每对数(10)拷贝Xy/毫升)，24周VL(每对数(10)拷贝/毫升1.74；95%可信区间，每对数(10)拷贝/毫升1.48-2.04)，以及最近的VL(每对数(10)拷贝/毫升HR 5 1.89；95%可信区间：1.63-2.20每对数(10个拷贝/毫升)与死亡率增加相关。当同时评估VL指标并控制其他协变量时，病毒血症复制年数增加死亡风险(HR=1.44/log(10)Copy/mL；95%CI，1.07~1.94/log(10)Copy/mL)，而没有横断面VL指标与死亡率独立相关。病毒血症复制年数预测了接受ART治疗的患者的全因死亡率，独立于传统的横断面VL测量和时间更新的CD4+T淋巴细胞计数，表明累积的艾滋病毒复制造成的损害与其对免疫缺陷程度的影响无关。
Background. Cross-sectional plasma human immunodeficiency virus (HIV) viral load (VL) measures have proven invaluable for clinical and research purposes. However, cross-sectional VL measures fail to capture cumulative plasma HIV burden longitudinally. We evaluated the cumulative effect of exposure to HIV replication on mortality following initiation of combination antiretroviral therapy (ART).Methods. We included treatment-naive HIV-infected patients starting ART from 2000 to 2008 at 8 Center for AIDS Research Network of Integrated Clinical Systems sites. Viremia copy-years, a time-varying measure of cumulative plasma HIV exposure, were determined for each patient using the area under the VL curve. Multivariable Cox models were used to evaluate the independent association of viremia copy-years for all-cause mortality.Results. Among 2027 patients contributing 6579 person-years of follow-up, the median viremia copy-years was 5.3 log(10) copy X y/mL (interquartile range: 4.9-6.3 log(10) copy X y/mL), and 85 patients (4.2%) died. When evaluated separately, viremia copy-years (hazard ratio [HR] = 1.81 per log(10) copy X y/mL; 95% confidence interval [CI], 1.51-2.18 per log(10) copy X y/mL), 24-week VL (1.74 per log(10) copies/mL; 95% CI, 1.48-2.04 per log(10) copies/mL), and most recent VL (HR 5 1.89 per log(10) copies/mL; 95% CI: 1.63-2.20 per log(10) copies/mL) were associated with increased mortality. When simultaneously evaluating VL measures and controlling for other covariates, viremia copy-years increased mortality risk (HR = 1.44 per log(10) copy X y/mL; 95% CI, 1.07-1.94 per log(10) copy X y/mL), whereas no cross-sectional VL measure was independently associated with mortality.Conclusions. Viremia copy-years predicted all-cause mortality independent of traditional, cross-sectional VL measures and time-updated CD4+ T-lymphocyte count in ART-treated patients, suggesting cumulative HIV replication causes harm independent of its effect on the degree of immunodeficiency.