Brunet-François C, Taieb A, Masquelier B, Le Moing V, Lewden C, Dellamonica P, Cuzin L, Allavena C, Spire B, Chêne G, Raffi F
Maladies Infectieuses et Tropicales, Hôtel-Dieu, Nantes, France.
Med Mal Infect. 2007 Mar;37(3):172-7. doi: 10.1016/j.medmal.2006.11.003. Epub 2007 Jan 17.
This study was made to determine the immunovirological outcome and tolerance to lopinavir/ritonavir (LPV/r) in HIV-infected protease inhibitors-experienced patients with long-term virological failure.
Prospective follow-up was implemented for the French cohort ANRS CO8 Aproco-Copilote of 121 patients starting an LPV/r-containing regimen after a median duration of virological failure of 30.6 months. At baseline the median HIV-RNA plasma level was 4.1 log(10) copies/ml and the median CD4 cell count was 273/mm(3).
On initiation of LPV/r, these patients were heavily pre-treated: 62% had received at least 4 NRTI, 65% at least 1 NNRTI, and 33% at least 3 PI. On prescription of LPV/r, the associated antiretroviral regimen was: no drug to which patients were previously naïve in 49 cases (40%), at least one new drug in 72 cases: 1 NRTI (n=42), 2 NRTI (n=22), 1 NNRTI (n=10), at least one new PI (n=6), enfuvirtide (n=2). The median HIV-RNA level was 2 log(10) copies/ml at M4 and M12, 1.7 log(10) copies/ml at M24 with respectively 74, 71 and 85% of patients achieving plasma HIV-RNA below 2.7 log(10) copies/ml. The median CD4 cell count was 385 and 429/mm(3) at M12 and M24 respectively. Among patients with genotypic testing at the time of LPV/r initiation, Ninety-five percent had at the most 5 protease mutations known to reduce LPV/r susceptibility. Thirty serious adverse events were reported but only 6 were related to LPV/r.
The use of LPV/r in HIV-infected patients failing multiple antiretroviral regimens provided a potent and durable immunovirological response.
本研究旨在确定长期病毒学失败的、曾使用过蛋白酶抑制剂的HIV感染患者使用洛匹那韦/利托那韦（LPV/r）后的免疫病毒学结果及耐受性。
对法国队列ANRS CO8 Aproco-Copilote的121例患者进行前瞻性随访，这些患者在病毒学失败的中位持续时间为30.6个月后开始使用含LPV/r的方案。基线时，血浆HIV-RNA水平中位数为4.1 log(10)拷贝/ml，CD4细胞计数中位数为273/mm³。
开始使用LPV/r时，这些患者接受过大量的前期治疗：62%接受过至少4种核苷类逆转录酶抑制剂（NRTI），65%接受过至少1种非核苷类逆转录酶抑制剂（NNRTI），33%接受过至少3种蛋白酶抑制剂（PI）。在使用LPV/r时，相关的抗逆转录病毒方案为：49例（40%）患者没有使用过之前未用过的药物，72例患者使用了至少一种新药：1种NRTI（n = 42），2种NRTI（n = 22），1种NNRTI（n = 10），至少一种新的PI（n = 6），恩夫韦肽（n = 2）。在第4个月和第12个月时，HIV-RNA水平中位数为2 log(10)拷贝/ml，在第24个月时为1.7 log(10)拷贝/ml，分别有74%、71%和85%的患者血浆HIV-RNA低于2.7 log(10)拷贝/ml。在第12个月和第24个月时，CD4细胞计数中位数分别为385和429/mm³。在开始使用LPV/r时进行基因检测的患者中，95%最多有5种已知会降低LPV/r敏感性的蛋白酶突变。报告了30起严重不良事件，但只有6起与LPV/r有关。
在多种抗逆转录病毒方案治疗失败的HIV感染患者中使用LPV/r可产生有效且持久的免疫病毒学反应。
