Interruption of combination antiretroviral therapy and risk of clinical disease progression to AIDS or death
Interruption of combination antiretroviral therapy and risk of clinical disease progression to AIDS or death
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DOI：
10.1111/j.1468-1293.2007.00436.x
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发表时间：
2007-03-01
期刊：
影响因子：
3
通讯作者：
Lundgren, J. D.
中科院分区：
文献类型：
--
作者：
Olsen, C. Holkmann;Mocroft, A.;Lundgren, J. D.
目的比较联合抗逆转录病毒治疗(CART)中断3个月和未中断治疗3个月以上患者不同类别的CD4细胞计数和病毒载量的艾滋病/死亡发生率(IRS)，以确定临床进展为艾滋病/死亡的危险因素。测定胰岛素抵抗指数(IR)及感染危险因素。我们用Poisson回归模型评估了感染和艾滋病/死亡事件的发生率比(IRR)。结果在纳入研究的3811名患者中，26%的人在CART之前是幼稚的。启动CART的中位数为1997年7月，CD_4细胞数中位数为226个/亩L，病毒载量中位数为4.36log(10)HIV-1RNA拷贝数/毫升。我们观察到1243次中断和403次艾滋病事件/死亡。艾滋病/死亡的IR在CD4细胞计数较低或病毒载量较高的患者中较高，与感染指数无关。在调整基线因素后，感染组艾滋病/死亡的IR显著高于非感染组[IRR2.63；95%可信区间(CI)2.01~3.44；P<；0.0001]；这可以用目前的CD_4细胞计数和病毒载量来解释，因为CD_4细胞计数和病毒载量调整后的IR为1.14(95%CI为0.86~1.51；P=0.37)。在TI组中，当前CD_4细胞数为200个/亩L的患者的艾滋病/死亡风险是CD_4细胞数为200~350个/亩L的患者的3倍，而CD_4细胞数为~350个/亩的L患者的疾病进展风险是T_4细胞数为200个/亩的患者的4倍。停止所有CART方案3个月或更长时间的患者，艾滋病/死亡的风险增加2倍以上。在经历感染的患者中，那些CD4细胞计数低、病毒载量高或有艾滋病病史的患者患艾滋病/死亡的风险增加。因此，如果发生感染，应予以劝阻和密切监测。
Objectives The aim of the study was to compare incidence rates (IRs) of AIDS/death in patients with and without treatment interruption (TI) of combination antiretroviral therapy (cART) for periods of 3 months or more for different categories of CD4 cell count and viral load, and to determine risk factors for clinical progression to AIDS/death.Methods Patients starting cART with a CD4 cell count and a viral load available within 6 months of starting cART were included in the study. The IR and risk factors of TI were determined. We assessed the incidence rate ratios (IRRs) for TI and AIDS/death events using Poisson regression models.Results Of 3811 patients included in the study, 26% were ART-naive prior to cART. The median date of starting cART was July 1997, the median CD4 cell count was 226 cells/mu L and the median viral load was 4.36 log(10) HIV-1 RNA copies/mL. We observed 1243 interruptions and 403 AIDS-events/deaths. The IR of AIDS/death was higher in patients with lower CD4 cell counts or higher viral loads, regardless of TI. After adjusting for baseline factors, the IR of AIDS/death was significantly higher in the TI group than in the non-TI group [IRR 2.63; 95% confidence interval (CI) 2.01-3.44; P < 0.0001]; this could be explained by current CD4 cell counts and viral loads, as the CD4 cell count- and viral load-adjusted IRR was 1.14 (95% CI 0.86-1.51; P=0.37). Within the TI group, patients with a current CD4 cell count of < 200 cells/mu L had a 3-fold higher risk of AIDS/death than those with a CD4 cell count of 200-350 cells/mu L, whereas patients with a current CD4 cell count of > 350 cells/mu L had a 4-fold lower risk of disease progression.Conclusions TI is common in clinical practice. The risk of AIDS/death increased more than 2-fold for patients stopping all cART regimen drugs for 3 months or more. Among patients experiencing a TI, those with low CD4 cell counts, high viral loads or prior AIDS had an increased risk of AIDS/death. Hence, TI should be discouraged and closely monitored if it occurs.