病毒血症持续时间可预测开始抗逆转录病毒治疗的初治 HIV 感染患者的死亡率。
Viremia copy-years predicts mortality among treatment-naive HIV-infected patients initiating antiretroviral therapy.
机构信息
Department of Medicine, Division of Infectious Diseases, University of Alabama, Birmingham, AL, USA.
出版信息
Clin Infect Dis. 2011 Nov;53(9):927-35. doi: 10.1093/cid/cir526. Epub 2011 Sep 2.
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 log₁₀ copy × y/mL (interquartile range: 4.9-6.3 log₁₀ copy × y/mL), and 85 patients (4.2%) died. When evaluated separately, viremia copy-years (hazard ratio [HR] = 1.81 per log₁₀ copy × y/mL; 95% confidence interval [CI], 1.51-2.18 per log(10) copy × y/mL), 24-week VL (1.74 per log₁₀ copies/mL; 95% CI, 1.48-2.04 per log₁₀ copies/mL), and most recent VL (HR = 1.89 per log₁₀ copies/mL; 95% CI: 1.63-2.20 per log₁₀ 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 log₁₀ copy × y/mL; 95% CI, 1.07-1.94 per log₁₀ copy × 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.
背景
横断面血浆人类免疫缺陷病毒 (HIV) 病毒载量 (VL) 测量在临床和研究方面已被证明具有重要价值。然而，横断面 VL 测量无法从纵向角度捕捉累积的血浆 HIV 负担。我们评估了暴露于 HIV 复制对开始联合抗逆转录病毒治疗 (ART) 后死亡率的累积影响。
方法
我们纳入了 2000 年至 2008 年在 8 个艾滋病研究网络综合临床系统中心开始接受 ART 的治疗初治 HIV 感染患者。每位患者的病毒血症拷贝年数（累积血浆 HIV 暴露的时变测量）使用 VL 曲线下面积确定。多变量 Cox 模型用于评估所有原因死亡率与病毒血症拷贝年数的独立关联。
结果
在 2027 名患者中，有 6579 人年的随访，中位病毒血症拷贝年数为 5.3 log₁₀ 拷贝 × y/mL（四分位距：4.9-6.3 log₁₀ 拷贝 × y/mL），有 85 名患者（4.2%）死亡。分别评估时，病毒血症拷贝年数（危险比 [HR] = 每 log₁₀ 拷贝 × y/mL 增加 1.81；95%置信区间 [CI]：每 log(10) 拷贝 × y/mL 增加 1.51-2.18），24 周 VL（每 log₁₀ 拷贝/mL 增加 1.74；95%CI：每 log₁₀ 拷贝/mL 增加 1.48-2.04），和最近的 VL（HR = 每 log₁₀ 拷贝/mL 增加 1.89；95%CI：每 log₁₀ 拷贝/mL 增加 1.63-2.20）与死亡率增加相关。当同时评估 VL 测量值并控制其他协变量时，病毒血症拷贝年数增加了死亡率风险（HR = 每 log₁₀ 拷贝 × y/mL 增加 1.44；95%CI：每 log₁₀ 拷贝 × y/mL 增加 1.07-1.94），而传统的横断面 VL 测量值均与死亡率无独立相关性。
结论
病毒血症拷贝年数独立于传统的、横断面的 VL 测量值和接受 ART 治疗患者的时间更新的 CD4+T 淋巴细胞计数预测全因死亡率，提示累积的 HIV 复制造成的危害独立于其对免疫缺陷程度的影响。
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