Voigt E, Wasmuth J-C, Vogel M, Mauss S, Schmutz G, Kaiser R, Rockstroh J-K
Department of Internal Medicine, University of Bonn, Sigmund Freud Str. 25, D-53105, Bonn, Germany.
Infection. 2004 Apr;32(2):82-8. doi: 10.1007/s15010-004-3059-3.
Within this open-label, uncontrolled prospective trial we evaluated safety, efficacy and development of genotypic resistance under the new protease inhibitor lopinavir/ritonavir (LPV/r) in antiretroviral (ARV) HIV patients.
58 patients with virological failure under their current ARV therapy were started on a LPV/r containing regimen. Median baseline HIV RNA and CD4 count were 4.6 log(10) cps/ml (range 2.1-6.4) and 128 x 10(6)/l (0-767), respectively. CD4 count, HIV RNA and metabolic parameters were assessed at weeks 0, 4, 8, 12, 16, 24, 32, 40, 48. Genotypic resistance testing was performed at baseline and again at weeks 12, 24 and 48 in the event of virological failure.
Until week 48, viral load (VL) decreased by a median of 1.9 log(10) cps/ml (-0.8-3.8). A VL below 80 cps/ml was found in 20/58 patients (34.5%) at week 48. In parallel, CD4 cells increased to a median of 332 x 10(6)/l (8-905). Nine patients discontinued study treatment. At 48 weeks, median triglyceride and cholesterol levels increased significantly. While the median number of overall protease mutations at baseline was four in all patients, it was six in patients virologically failing on LPV/r. The average number of mutations increased significantly to eight at week 48. Several mutations were detected considerably more often in the event of failure than in response to treatment, e. g. at amino acid positions 10, 24, 54, 71, 82, 84.
LPV/r is effective in heavily pretreated patients. Discontinuation due to adverse events is infrequent. No individual mutation can be associated with failure on LPV/r. However, a greater number of protease mutations at baseline is associated with poorer treatment outcome and several mutations seem to be related to treatment failure.
在这项开放标签、非对照的前瞻性试验中，我们评估了新型蛋白酶抑制剂洛匹那韦/利托那韦（LPV/r）在抗逆转录病毒（ARV）HIV患者中的安全性、疗效以及基因型耐药性的发展情况。
58例当前抗逆转录病毒治疗出现病毒学失败的患者开始接受含LPV/r的治疗方案。基线时HIV RNA中位数和CD4细胞计数分别为4.6 log(10) cps/ml（范围2.1 - 6.4）和128×10⁶/l（0 - 767）。在第0、4、8、12、16、24、32、40、48周评估CD4细胞计数、HIV RNA和代谢参数。如果出现病毒学失败，在基线以及第12、24和48周再次进行基因型耐药性检测。
至第48周，病毒载量（VL）中位数下降了1.9 log(10) cps/ml（-0.8 - 3.8）。在第48周时，58例患者中有20例（34.5%）的VL低于80 cps/ml。与此同时，CD4细胞增加至中位数332×10⁶/l（8 - 905）。9例患者中断研究治疗。在48周时，甘油三酯和胆固醇水平中位数显著升高。所有患者基线时蛋白酶总体突变中位数为4个，而在LPV/r治疗出现病毒学失败的患者中为6个。到第48周时，平均突变数显著增加至8个。与治疗有反应相比，在治疗失败时检测到几种突变的频率明显更高，例如在氨基酸位置10、24、54、71、82、84处。
LPV/r对经过大量治疗的患者有效。因不良事件导致的停药情况不常见。没有单个突变可与LPV/r治疗失败相关。然而，基线时蛋白酶突变数量较多与治疗效果较差相关，并且几种突变似乎与治疗失败有关。
