Servicio de Enfermedades Infecciosas, Hospitales Universitarios Virgen del Rocío, Instituto de Biomedicina de Sevilla, Seville, Spain.
AIDS Res Ther. 2010 Mar 17;7:5. doi: 10.1186/1742-6405-7-5.
Ritonavir-boosted saquinavir (SQVr) is nowadays regarded as an alternative antiretroviral drug probably due to several drawbacks, such as its high pill burden, twice daily dosing and the requirement of 200 mg ritonavir when given at the current standard 1000/100 mg bid dosing. Several once-daily SQVr dosing schemes have been studied with the 200 mg SQV old formulations, trying to overcome some of these disadvantages. SQV 500 mg strength tablets became available at the end of 2005, thus facilitating a once-daily regimen with fewer pills, although there is very limited experience with this formulation yet.
Prospective, multicentre study in which efficacy, safety and pharmacokinetics of a regimen of once-daily SQVr 1500/100 mg plus 2 NRTIs were evaluated under routine clinical care conditions in either antiretroviral-naïve patients or in those with no previous history of antiretroviral treatments and/or genotypic resistance tests suggesting SQV resistance. Plasma SQV trough levels were measured by HPLV-UV.
Five hundred and fourteen caucasian patients were included (47.2% coinfected with hepatitis C and/or B virus; 7.8% with cirrhosis). Efficacy at 52 weeks (plasma RNA-HIV <50 copies/ml) was 67.7% (CI95: 63.6 - 71.7%) by intention-to-treat, and 92.2% (CI95: 89.8 - 94.6%) by on-treatment analysis. The reasons for failure were: dropout or loss to follow-up (18.4%), virological failure (7.8%), adverse events (3.1%), and other reasons (4.6%). The high rate of dropout may be explained by an enrollment and follow-up under routine clinical care condition, and a population with a significant number of drug users. The median SQV Cmin (n = 49) was 295 ng/ml (range, 53-2172). The only variable associated with virological failure in the multivariate analysis was adherence (OR: 3.36; CI95, 1.51-7.46, p = 0.003).
Our results suggests that SQVr (1500/100 mg) once-daily plus 2 NRTIs is an effective regimen, without severe clinical adverse events or hepatotoxicity, scarce lipid changes, and no interactions with methadone. All these factors and its once-daily administration suggest this regimen as an appropriate option in patients with no SQV resistance-associated mutations.
如今，利托那韦增强的沙奎那韦（SQVr）被认为是一种替代抗逆转录病毒药物，可能是由于其存在一些缺点，如高剂量、每日两次给药以及当目前标准的 1000/100mg bid 剂量给药时需要 200mg 利托那韦。已经研究了几种每日一次的 SQVr 给药方案，使用旧的 200mg SQV 制剂，试图克服其中一些缺点。2005 年底，SQV500mg 片剂问世，从而可以使用更少的药丸进行每日一次的治疗方案，尽管目前对此种制剂的经验非常有限。
这是一项前瞻性、多中心研究，在常规临床护理条件下，评估每日一次 SQVr1500/100mg 加 2 种 NRTIs 方案治疗初治患者或既往无抗逆转录病毒治疗史且无基因耐药测试提示 SQV 耐药患者的疗效、安全性和药代动力学。通过高压液相色谱法-紫外分光光度法（HPLV-UV）测量 SQV 谷浓度。
共纳入 514 名白种人患者（47.2%合并丙型肝炎和/或乙型肝炎病毒感染，7.8%合并肝硬化）。按照意向治疗分析，52 周时的疗效（血浆 RNA-HIV<50 拷贝/ml）为 67.7%（95%CI：63.6-71.7%），根据治疗分析为 92.2%（95%CI：89.8-94.6%）。失败的原因包括：失访或随访丢失（18.4%）、病毒学失败（7.8%）、不良事件（3.1%）和其他原因（4.6%）。高失访率可能是由于在常规临床护理条件下进行入组和随访，以及人群中有大量药物使用者。49 例患者的中位 SQV Cmin（n=49）为 295ng/ml（范围：53-2172）。多变量分析中，唯一与病毒学失败相关的变量是依从性（OR：3.36；95%CI：1.51-7.46，p=0.003）。
我们的研究结果表明，SQVr（1500/100mg）每日一次加 2 种 NRTIs 是一种有效的方案，无严重临床不良事件或肝毒性，脂质变化轻微，与美沙酮无相互作用。所有这些因素及其每日一次的给药方式表明，对于无 SQV 耐药相关突变的患者，该方案是一种合适的选择。
