Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
PLoS Med. 2010 Feb 23;7(2):e1000239. doi: 10.1371/journal.pmed.1000239.
CD4 cell count is a strong predictor of the subsequent risk of AIDS or death in HIV-infected patients initiating combination antiretroviral therapy (cART). It is not known whether the rate of CD4 cell decline prior to therapy is related to prognosis and should, therefore, influence the decision on when to initiate cART.
We carried out survival analyses of patients from the 23 cohorts of the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) collaboration with a known date of HIV seroconversion and with at least two CD4 measurements prior to initiating cART. For each patient, a pre-cART CD4 slope was estimated using a linear mixed effects model. Our primary outcome was time from initiating cART to a first new AIDS event or death. We included 2,820 treatment-naïve patients initiating cART with a median (interquartile range) pre-cART CD4 cell decline of 61 (46-81) cells/microl per year; 255 patients subsequently experienced a new AIDS event or death and 125 patients died. In an analysis adjusted for established risk factors, the hazard ratio for AIDS or death was 1.01 (95% confidence interval 0.97-1.04) for each 10 cells/microl per year reduction in pre-cART CD4 cell decline. There was also no association between pre-cART CD4 cell slope and survival. Alternative estimates of CD4 cell slope gave similar results. In 1,731 AIDS-free patients with >350 CD4 cells/microl from the pre-cART era, the rate of CD4 cell decline was also not significantly associated with progression to AIDS or death (hazard ratio 0.99, 95% confidence interval 0.94-1.03, for each 10 cells/microl per year reduction in CD4 cell decline).
The CD4 cell slope does not improve the prediction of clinical outcome in patients with a CD4 cell count above 350 cells/microl. Knowledge of the current CD4 cell count is sufficient when deciding whether to initiate cART in asymptomatic patients. Please see later in the article for the Editors' Summary.
CD4 细胞计数是预测 HIV 感染者开始联合抗逆转录病毒治疗（cART）后 AIDS 或死亡风险的强有力指标。尚不清楚治疗前 CD4 细胞下降的速度是否与预后相关，因此应影响开始 cART 的决策。
我们对来自 CASCADE（欧洲协同行动以血清转换和 AIDS 及死亡）合作的 23 个队列的患者进行了生存分析，这些患者的 HIV 血清转换日期已知，且在开始 cART 前至少有两次 CD4 测量。对于每个患者，使用线性混合效应模型估计 cART 前的 CD4 斜率。我们的主要结局是从开始 cART 到首次新发 AIDS 事件或死亡的时间。我们纳入了 2820 名开始 cART 的治疗初治患者，中位（四分位间距）cART 前 CD4 细胞每年下降 61（46-81）个细胞/微升；255 名患者随后发生新发 AIDS 事件或死亡，125 名患者死亡。在调整了已确立的危险因素的分析中，cART 前 CD4 细胞下降每减少 10 个细胞/微升，AIDS 或死亡的风险比为 1.01（95%置信区间 0.97-1.04）。cART 前 CD4 细胞斜率与生存之间也没有关联。替代的 CD4 细胞斜率估计也得出了类似的结果。在来自 cART 前时代的 1731 名 CD4 细胞>350 个/微升的 AIDS 无进展患者中，CD4 细胞下降率也与进展为 AIDS 或死亡无关（CD4 细胞下降每减少 10 个细胞/微升，风险比为 0.99，95%置信区间 0.94-1.03）。
在 CD4 细胞计数高于 350 个/微升的患者中，CD4 细胞斜率不能改善临床结局的预测。在决定是否对无症状患者开始 cART 时，目前的 CD4 细胞计数知识是足够的。请在文章后面查看编辑总结。
