Infectious Diseases Unit at Medical Department No. 2, Hospital of the Johann Wolfgang Goethe-University, Frankfurt, Germany.
Med Microbiol Immunol. 2013 Apr;202(2):117-24. doi: 10.1007/s00430-012-0276-8. Epub 2012 Sep 15.
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 ≥500 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.
为了探索 CD4 细胞和病毒的演变与 HIV-1 复制的不同水平之间的关系，我们对接受基于蛋白酶抑制剂（PI）的抗逆转录病毒治疗的成年 HIV-1 感染队列患者进行了回顾性分析。这些患者接受了每日剂量的沙奎那韦（2000mg）、利托那韦（200mg）和洛匹那韦（800mg）或阿扎那韦（300mg）的历史挽救性治疗，治疗时间超过 36 周。我们对最高可检测到的病毒载量进行了分析，直到第 96 周，并根据病毒载量水平将患者分为以下几组：始终<50 拷贝/ml（1）、50-199 拷贝/ml（2）、200-499 拷贝/ml（3）和≥500 拷贝/ml（4）。共评估了 126 例患者；基线时，中位 CD4 细胞计数为 204/mm3，HIV-1 RNA 为 5.13 Log10 拷贝/ml，HIV-1 感染时间为 11.7 年。根据 43%、30%、7%和 20%的比例，患者分别被分配到组 1-4。中位观察时间为 136 周（范围：38-304）；在第 48/96 周时，组 1-4 的 CD4 细胞增加分别为+88/+209、+209/+349、+67/+300 和+114.5/+128。在将数据拟合到线性固定效应模型后，组 1 的 CD4 斜率呈连续上升趋势，组 2 也呈上升趋势，而组 3-4 则呈下降趋势（p = 0.0006）。在组 4 的 25 名患者中，有 5 名患者在蛋白酶抑制剂治疗失败前和后出现了主要 IAS-USA 蛋白酶突变，而有 10 名患者出现了次要突变，且数量保持稳定（n = 18）。在双重增强的 PI 治疗中，在第 96 周时，始终无法检测到病毒或检测到低病毒载量的患者的 CD4 细胞增加情况相似。病毒检测>200 拷贝/ml 与 CD4 细胞斜率下降和主要突变的出现相关，支持将其作为 PI 治疗中病毒学失败的定义基准。
