Impact of HIV-1 replication on immunological evolution during long-term dual-boosted protease inhibitor therapy
Impact of HIV-1 replication on immunological evolution during long-term dual-boosted protease inhibitor therapy
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DOI：
10.1007/s00430-012-0276-8
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发表时间：
2013-04-01
影响因子：
5.4
通讯作者：
Bickel, Markus
中科院分区：
文献类型：
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作者：
Stephan, Christoph;Bartha, Valentin;Bickel, Markus
探讨在基于蛋白酶抑制剂(PI)的抗逆转录病毒治疗中观察到的CD4细胞和病毒进化与不同水平的HIV-1复制的关系。对接受过挽救治疗的成年HIV-1感染者进行了36周的回顾性分析，以确定最高可检测到的病毒载量至96周，并根据病毒载量水平进行分组：始终50拷贝/毫升(1)、50-199拷贝/毫升(2)、200-499拷贝/毫升(3)和百万分之500拷贝/毫升(4)。共有126名患者接受了评估；基线时，CD4细胞计数的中位数为204/mm(3)，HIV-1RNA为5.13log10-Copies/ml，既往感染HIV-1的持续时间为11.7年。将患者按43%、30%、7%和20%分配到1-4组。中位观察时间为136周(范围为38-304周)，在48/96周时，第1~4组的CD_4细胞增值分别为+88/+209、+209/+349、+67/+300和+114.5/+128。在线性固定效应模型中拟合数据后，组1上升的CD_4斜率持续增加，组2类似，3-4组明显减小(p=0.0006)。在来自第4组的25名个体中，在PI治疗失败前后，IAS-USA蛋白水解酶主要突变的患者数量从5人增加到10人，而微小突变保持稳定(n=18)。在双强化PI治疗中，在总是检测不到或检测到低病毒载量的患者中，第96周的CD4细胞增加是相似的。病毒检测>；200拷贝/毫升与CD4细胞斜率降低和主要突变的出现有关，支持将其作为PI治疗病毒学失败定义的基准。
To explore CD4-cell and viral evolution in relation to different levels of HIV-1 replication, as observed during protease inhibitor (PI)-based antiretroviral therapy. Adult HIV-1 infected cohort patients, receiving historical salvage therapy with daily doses of saquinavir (2,000 mg), ritonavir (200 mg) and either lopinavir (800 mg) or atazanavir (300 mg) for > 36 weeks were retrospectively analysed for highest detectable viral load up to week 96 and assigned to groups according to the viral load level: always < 50 copies/ml (1), 50-199 copies/ml (2), 200-499 copies/ml (3) and a parts per thousand yen500 copies/ml (4). A total of 126 patients were evaluated; at baseline, median CD4-cell count was 204/mm(3), HIV-1 RNA was 5.13 Log10-copies/ml and duration of prior HIV-1 infection was 11.7 years. Patients were assigned by 43, 30, 7 and 20 % to groups 1-4. Median observation time was 136 weeks (range: 38-304); at weeks 48/96, the CD4-cell gains for groups 1-4 were +88/+209, +209/+349, +67/+300 and +114.5/+ 128, respectively. After fitting data in a linear fixed effect model, ascending CD4 slopes were continuously increasing for group 1, similarly for 2 and clearly decreasing for 3-4 (p = 0.0006). Of 25 individuals from group 4, patient number with major IAS-USA protease mutations increased from 5 to 10 before and after failing PI therapy, whereas minor mutations remained stable (n = 18). On double-boosted PI therapy, CD4-cell increases through week 96 were similar for patients at always undetectable or with detection of low viral load. Viral detection > 200 copies/ml was associated with decreasing CD4-cell slopes and emergence of major mutations, supporting this as benchmark for virological failure definition on PI therapy.