AP-HP, Pitié-Salpêtrière Hospital, INSERM U943 and Pierre et Marie Curie University, Paris, France.
J Antimicrob Chemother. 2012 Oct;67(10):2487-93. doi: 10.1093/jac/dks226. Epub 2012 Jun 25.
This observational study was requested by French health authorities to determine the impact of lopinavir/ritonavir (Kaletra(®)) on antiretroviral resistance in clinical practice. Virological failures of lopinavir/ritonavir and their effects on the resistance to protease inhibitors and reverse transcriptase inhibitors were evaluated in protease inhibitor-experienced patients.
Virological failure was defined as an HIV-1 plasma viral load >50 copies/mL after at least 3 months of lopinavir/ritonavir-containing antiretroviral therapy. For all patients, a resistance genotypic test was available at failure and before lopinavir/ritonavir treatment. Data from 72 patients with inclusion criteria were studied.
The mean viral load at baseline was 4 log(10) copies/mL (1.6-6.5). Mutations in the protease gene significantly selected between baseline and failure were L10V, K20R, L33F, M36I, I47V, I54V, A71V and I85V (P < 0.05). Patients who had more than seven protease inhibitor mutations at baseline showed a significantly increased risk of occurrence of protease inhibitor mutations. The proportion of viruses susceptible to atazanavir, fosamprenavir and darunavir decreased significantly between baseline and failure (P < 0.05). Among patients with a virus susceptible to atazanavir at day 0, 26% (n = 14) exhibited a virus resistant or possibly resistant at the time of failure. This proportion was 32% (n = 16) for fosamprenavir and 16% (n = 7) for darunavir.
A darunavir-based regimen appears to be a sequential option in the case of lopinavir/ritonavir failure. To compare and determine the best treatment sequencing, similar studies should be performed for darunavir/ritonavir and atazanavir/ritonavir.
这项观察性研究是应法国卫生当局的要求进行的，旨在确定洛匹那韦/利托那韦（克力芝(®)）在临床实践中对艾滋病病毒耐药性的影响。在有蛋白酶抑制剂治疗经验的患者中，评估了洛匹那韦/利托那韦的病毒学失败及其对蛋白酶抑制剂和逆转录酶抑制剂耐药性的影响。
病毒学失败定义为洛匹那韦/利托那韦联合抗病毒治疗至少 3 个月后 HIV-1 血浆病毒载量>50 拷贝/ml。所有患者在失败时和洛匹那韦/利托那韦治疗前都有耐药基因型检测。对符合纳入标准的 72 例患者的数据进行了研究。
基线时的平均病毒载量为 4 对数（10）拷贝/ml（1.6-6.5）。在基线和失败之间，蛋白酶基因的突变明显选择为 L10V、K20R、L33F、M36I、I47V、I54V、A71V 和 I85V（P<0.05）。基线时具有超过 7 个蛋白酶抑制剂突变的患者发生蛋白酶抑制剂突变的风险显著增加。与基线相比，对阿扎那韦、福沙那韦和达芦那韦敏感的病毒比例显著下降（P<0.05）。在基线时对阿扎那韦敏感的患者中，26%（n=14）在失败时出现病毒耐药或可能耐药。这一比例在福沙那韦组为 32%（n=16），达芦那韦组为 16%（n=7）。
在洛匹那韦/利托那韦失败的情况下，基于达芦那韦的方案似乎是一种后续选择。为了比较并确定最佳的治疗顺序，应该对达芦那韦/利托那韦和阿扎那韦/利托那韦进行类似的研究。
