Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes
Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes
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DOI：
10.1016/s0140-6736(04)16589-6
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发表时间：
2004-07-03
期刊：
影响因子：
168.9
通讯作者：
Esposito, R
中科院分区：
文献类型：
--
作者：
Ledergerber, B;Lundgren, JD;Esposito, R
背景 对于接触多种药物后 HIV 复制未受到抑制的患者，其治疗策略仍不清楚。我们的目的是评估经历过三级病毒学失败的患者的病毒载量、CD4细胞计数和临床结果之间的相互关系。方法我们对来自欧洲、北美和澳大利亚的13个HIV队列进行了协作联合分析，其中涉及经历过三级病毒学失败的患者（病毒载量> 1000拷贝/毫升，持续> 4个月）。回归分析用于量化 CD4 细胞计数斜率、HIV-1 RNA 浓度、治疗信息和人口特征之间的关联。通过 Cox 比例风险模型对死亡预测因素进行了分析。研究结果包括 2488 名患者。 2118 人 (85%) 已开始接受单一或双重治疗的抗逆转录病毒治疗。在 5015 人年的随访期间，有 276 名患者死亡（死亡率为 5.5/100 人年；3 年死亡风险为 15.3% (95% CI 13.5-17.3)。死亡风险受到最新 CD4 细胞计数的强烈影响，细胞计数低于 50 的相对风险为 15.8 (95% CI 9.28-27.0)每μL 与每μL 以上200 个细胞相比，最新的病毒载量无法独立预测。 死亡。对于任何给定的病毒载量，接受治疗的患者比未接受治疗的患者具有更有利的 CD4 细胞计数斜率。对于正在接受治疗且病毒载量稳定的患者，当当前病毒载量低于每毫升 10 000 拷贝或低于治疗结束值 1.5 log(10) 拷贝每毫升时，CD4 细胞计数有时会增加。 实现并维持每毫升 200 个以上的 CD4 细胞计数成为首要目标。维持病毒载量低于每毫升 10 000 拷贝或至少提供每毫升 1.5 log(10) 拷贝抑制低于治疗结束值的治疗方案似乎与 CD4 细胞计数明显下降无关。
Background Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure.Methods We undertook collaborative joint analysis of 13 HIV cohorts from Europe, North America, and Australia, involving patients who had had three-class virological failure (viral load >1000 copies per mL for >4 months). Regression analyses were used to quantify the associations between CD4-cell-count slope, HIV-1 RNA concentration, treatment information, and demographic characteristics. Predictors of death were analysed by Cox's proportional-hazards models.Findings 2488 patients were included. 2118 (85%) had started antiretroviral therapy with single or dual therapy. During 5015 person-years of follow-up, 276 patients died (mortality rate 5.5 per 100 person-years; 3-year mortality risk 15.3% (95% Cl 13.5-17.3). Risk of death was strongly influenced by the latest CD4-cell count with a relative hazard of 15.8 (95% CI 9.28-27.0) for counts below 50 cells per muL versus above 200 cells per muL. The latest viral load did not independently predict death. For any given viral load, patients on treatment had more favourable CD4-cell-count slopes than those off treatment. For patients on treatment and with stable viral load, CD4-cell counts tended to be increasing at times when the current viral load was below 10 000 copies per mL or 1.5 log(10) copies per mL below off-treatment values.Interpretation In patients for whom viral-load suppression to below the level of detection is not possible, achievement and maintenance of a CD4-cell count above 200 per muL becomes the primary aim. Treatment regimens that maintain the viral load below 10 000 copies per mL or at least provide 1.5 log(10) copies per mL suppression below the off-treatment value do not seem to be associated with appreciable CD4-cell-count decline.