Staszewski Schlomo, Babacan Errol, Stephan Christoph, Haberl Annette, Carlebach Amina, Gute Peter, Klauke Stephan, Hermschulte Yvonne, Stuermer Martin, Dauer Brenda
Medical HIV Treatment & Research Unit, Hospital of the Johann Wolfgang Goethe University, Frankfurt, Germany.
J Antimicrob Chemother. 2006 Nov;58(5):1024-30. doi: 10.1093/jac/dkl375. Epub 2006 Sep 6.
To evaluate the virological, immunological and clinical responses to the boosted double protease inhibitor (PI) regimen combination of lopinavir/ritonavir and saquinavir ('LOPSAQ') without reverse transcriptase inhibitors (RTI) in HIV-positive patients who have few viable RTI treatment options.
Cohort study of 128 heavily pre-treated patients who were experiencing therapy failure on their current regimen due to RTI resistance and/or systemic toxicities. Patients with PI-resistance mutations or RTI toxicity underwent a structured treatment interruption (STI) (n=76) until virus reverted to wild-type or until resolution of toxicity symptoms. Baseline was defined as the time point when lopinavir/ritonavir plus saquinavir therapy was initiated. Virological response was defined as viral load<400 copies/mL at week 48.
A total of 78 (61%) patients experienced a virological response to therapy (ITT). Median viral load at baseline was 5.06 log10 copies/mL; at week 48 median was 2.16 log10 copies. Median CD4 at week 48 was 280 cells/mm3 compared with 172 cells at baseline. At week 48, 78/128 patients were still on therapy. In univariable analyses, significant predictors of virological response included higher CD4 count (P<0.001), lower viral load (P=0.002), less PI-experience (P=0.006) at baseline and fewer PI-resistance mutations (P=0.043) at end of prior failing regimen; in the multivariable analysis only higher CD4 count at baseline (P=0.009) and fewer number of drugs previously taken (P=0.003) could be specified as independent predictors for response.
The combination of lopinavir/ritonavir and saquinavir without RTIs is a potential option as salvage therapy for patients experiencing therapy failure due to RTI resistance or toxicity. This regimen may not be suitable for patients with very low baseline CD4 cell counts, very broad antiretroviral therapy experience or extensive PI-resistance mutations.
评估在几乎没有可行的逆转录酶抑制剂（RTI）治疗方案的HIV阳性患者中，洛匹那韦/利托那韦与沙奎那韦（“LOPSAQ”）组成的增强型双蛋白酶抑制剂（PI）方案（不含RTI）的病毒学、免疫学和临床反应。
对128例接受过大量治疗的患者进行队列研究，这些患者因RTI耐药和/或全身毒性而在当前治疗方案上出现治疗失败。有PI耐药突变或RTI毒性的患者接受结构化治疗中断（STI）（n = 76），直到病毒恢复为野生型或毒性症状消退。基线定义为开始洛匹那韦/利托那韦加沙奎那韦治疗的时间点。病毒学反应定义为第48周时病毒载量<400拷贝/毫升。
共有78例（61%）患者出现治疗的病毒学反应（意向性分析）。基线时病毒载量中位数为5.06 log10拷贝/毫升；第48周时中位数为2.16 log10拷贝。第48周时CD4中位数为280个细胞/立方毫米，而基线时为172个细胞。第48周时，78/128例患者仍在接受治疗。在单变量分析中，病毒学反应的显著预测因素包括较高的CD4计数（P<0.001）、较低的病毒载量（P = 0.002）、基线时较少的PI治疗经验（P = 0.006）以及先前失败治疗方案结束时较少的PI耐药突变（P = 0.043）；在多变量分析中，只有基线时较高的CD4计数（P = 0.009）和先前服用的药物数量较少（P = 0.003）可被指定为反应的独立预测因素。
洛匹那韦/利托那韦与沙奎那韦联合使用且不含RTI，对于因RTI耐药或毒性而出现治疗失败的患者，是一种潜在的挽救治疗选择。该方案可能不适用于基线CD4细胞计数极低、抗逆转录病毒治疗经验非常丰富或有广泛PI耐药突变的患者。
