Lopinavir/ritonavir as single-drug therapy for maintenance of HlV-1 viral suppression -: 48-week results of a randomized, controlled, open-label, proof-of-concept pilot clinical trial (OK study)
Lopinavir/ritonavir as single-drug therapy for maintenance of HlV-1 viral suppression -: 48-week results of a randomized, controlled, open-label, proof-of-concept pilot clinical trial (OK study)
复制标题
DOI：
10.1097/01.qai.0000180077.59159.f4
复制
发表时间：
2005-11-01
影响因子：
3.6
通讯作者：
Peña, JM
中科院分区：
文献类型：
--
作者：
Arribas, JR;Pulido, F;Peña, JM
目的：本研究评价了洛匹那韦/利托那韦单药治疗与持续托匹那韦/利托那韦和2种核苷类药物治疗HIV复制受抑制的HIV感染患者的维持效果。设计：随机、对照、开放标签、多中心、先导性临床试验。成年患者如果在接受蛋白酶抑制剂治疗时没有病毒学失败史，接受2种核苷+洛匹那韦/利托那韦（400/100 mg b.i.d.）结果：42例患者按1：1随机分配继续或停止核苷类药物治疗。在基线时，两组之间的中位CD 4细胞/μ L（基线或最低值）、HAART（高效抗逆转录病毒疗法）前HIV log（10）病毒血症或入组前HIV RNA < 50拷贝/mL的时间无显著差异。随访48周后，单药治疗组HIV RNA拷贝数保持在< 50/mL（意向治疗，M = F）的患者百分比为81%（95% CI：64%至98%），三联治疗组为95%（95% CI：86%至100%）; P = 0.34。单药治疗失败的患者的依从性明显低于单药治疗仍受到生命抑制的患者。单药治疗失败的患者没有表现出蛋白酶基因的原发性耐药突变，并成功地用预随机化核苷重新诱导。CD 4细胞/μ L的平均变化：+70（单药治疗）和+8（三联治疗）（P = 0.27）。两组的平均空腹血脂保持稳定。没有严重的不良事件observed.Conclusion：大多数维持洛匹那韦/利托那韦单药治疗的患者在48周后仍无法检测到病毒载量。洛匹那韦/利托那韦单药治疗的失败与蛋白酶基因中原发性耐药突变的发生无关，并且可以成功地重新引入先前的核苷。
Objective: This study evaluated maintenance with lopinavir/ritonavir monotherapy vs. continuing topinavir/ritonavir and 2 nucleosides in HIV-infected patients with suppressed HIV replication.Design: Randomized, controlled, open-label, multicenter, pilot clinical trial.Methods: Adult patients were eligible if they had no history of virologic failure while receiving a protease inhibitor, were receiving 2 nucleosides + lopinavir/ritonavir (400/100 mg b.i.d.) for > 1 month and had maintained serum HIV RNA < 50 copies/mL for > 6 months prior to enrollment.Results: Forty-two patients were randomly assigned 1:1 to continue or stop the nucleosides. At baseline there were no significant differences between groups in median CD4 cells/mu L (baseline or nadir), pre-HAART (highly active antiretroviral therapy) HIV log(10) viremia, or time with HIV RNA < 50 copies/mL prior to enrollment. After 48 weeks of follow-up, percentage of patients remaining at < 50 HIV RNA copies/mL (intention to treat, M = F) was 81% for the monotherapy group (95% CI: 64% to 98%) vs. 95% for the triple-therapy group (95% CI: 86% to 100%); P = 0.34. Patients in whom monotherapy failed had significantly worse adherence than patients who remained vitally suppressed on monotherapy. Monotherapy failures did not show primary resistance mutations in the protease gene and were successfully reinduced with prerandomization nucleosides. Mean change in CD4 cells/mu L: +70 (monotherapy) and +8 (triple) (P = 0.27). Mean serum fasting lipids remained stable in both groups. No serious adverse events were observed.Conclusion: Most of the patients maintained with lopinavir/ritonavir monotherapy remain with undetectable viral load after 48 weeks. Failures of lopinavir/ritonavir monotherapy were not associated with the development of primary resistance mutations in the protease gene and could be successfully reinduced adding back prior nucteosides.