Masuhr A, Mueller M, Simon V, Zwingers T, Kurowski M, Jessen H, Lauenroth-Mai E, Moll A, Schranz D, Moecklinghoff C, Arastéh K
Auguste-Viktoria-Hospital, TH of Free University Berlin, Germany.
Eur J Med Res. 2002 Aug 30;7(8):341-6.
To determine factors associated with virological failure during long-term treatment with the triple combination of saquinavir soft gel capsule, zalcitabine and zidovudine.
Open-label, prospective, multicentre study undertaken in private practices and the outpatient department of the Auguste-Viktoria-Hospital. A total of 95 patients with plasma HIV RNA > 5000 copies/ml who had received no more than 6 months pre-treatment with NRTIs and no prior PI therapy received saquinavir soft gel, zalcitabine and zidovudine for 52 weeks, before being randomly assigned to either remain on therapy or switch to nelfinavir, lamivudine and zidovudine for further 52 weeks.
Combination therapy with saquinavir, zalcitabine and zidovudine was found to be effective and well tolerated, with virological response to therapy maintained for up to 2 years. In patients responding to therapy, switching to a novel triple regimen did not result in a virological or immunological worsening, but it did not confer an additional clinical benefit. Factors predictive of early treatment failure (virological failure within 16 weeks of treatment initiation) included high viral load and presence of RT mutations at baseline (OR: 0.30, 95% CI 0.11 0.83 and OR 0.13, 95% CI 0.03 0.52, respectively), with baseline viral load and the development of genotypic mutations on therapy being predictive of late treatment failure (16 52 weeks; OR: 0.15, 95% 0.05 0.46 and OR: 0.26, 95% CI < 0.001 1.16, respectively). Plasma saquinavir concentration < 50 mg/ml at 4 weeks was also found to be an independent risk factor for both early and late treatment failure (OR: 1.80, 95% CI 1.23 2.64 and OR: 1.16, 95% CI 0.84 1.60, respectively).
While antiretroviral drug resistance appears to be a principal cause of treatment failure, other factors such as inadequate drug plasma concentrations also play a role.
确定在使用沙奎那韦软胶囊、扎西他滨和齐多夫定三联疗法进行长期治疗期间与病毒学失败相关的因素。
在私人诊所和奥古斯特 - 维多利亚医院门诊部进行的开放标签、前瞻性、多中心研究。共有95例血浆HIV RNA>5000拷贝/ml的患者，他们接受核苷类逆转录酶抑制剂（NRTIs）预处理不超过6个月且之前未接受蛋白酶抑制剂（PI）治疗，接受沙奎那韦软胶囊、扎西他滨和齐多夫定治疗52周，之后随机分配继续治疗或换用奈非那韦、拉米夫定和齐多夫定再治疗52周。
发现沙奎那韦、扎西他滨和齐多夫定联合治疗有效且耐受性良好，病毒学反应可持续长达2年。在对治疗有反应的患者中，换用新的三联疗法并未导致病毒学或免疫学恶化，但也未带来额外的临床益处。预测早期治疗失败（治疗开始后16周内病毒学失败）的因素包括高病毒载量和基线时存在逆转录酶（RT）突变（比值比[OR]分别为0.30，95%置信区间[CI] 0.11 - 0.83和OR 0.13，95% CI 0.03 - 0.52），基线病毒载量和治疗期间基因型突变的发生可预测晚期治疗失败（16 - 52周；OR分别为0.15，95% CI 0.05 - 0.46和OR 0.26，95% CI < 0.001 - 1.16）。还发现4周时血浆沙奎那韦浓度<50 mg/ml是早期和晚期治疗失败的独立危险因素（OR分别为1.80，95% CI 1.23 - 2.64和OR 1.16，95% CI 0.84 - 1.60）。
虽然抗逆转录病毒药物耐药性似乎是治疗失败的主要原因，但其他因素如药物血浆浓度不足也起作用。
