INSERM UMR-S 943 and University Pierre and Marie Curie (UPMC) Paris VI, Paris, France.
AIDS. 2010 Sep 24;24(15):2365-74. doi: 10.1097/QAD.0b013e32833dec20.
Darunavir/ritonavir (darunavir/r) maintenance strategy, in patients with suppressed HIV RNA viremia, is a potential long-term strategy to avoid nucleoside analogue toxicities and to reduce costs.
MONOtherapy Inhibitor protease is a prospective, open-label, noninferiority, 96-week safety and efficacy trial in virologically suppressed patients on triple therapy who were randomized to a darunavir/r triple drug regimen or darunavir/r monotherapy. The primary endpoint was the proportion of patients with HIV RNA less than 400 copies/ml at week 48; treatment failure was defined as two consecutive HIV RNA more than 400 copies/ml (time to loss of virologic response) or any change in treatment. The trial had 80% power to show noninferiority for the monotherapy arm (delta =-10%, 90% confidence interval).
A total of 242 patients were screened, 225 of whom were randomized. In the per protocol efficacy analysis, treatment success was 99% on darunavir/r triple drug versus 94% on darunavir/r monotherapy (delta = -4.9%, 90% confidence interval, from -9.1 to -0.8). Similar results were found in intent-to-treat population (92 versus 87.5%, delta = -4.5%, 90% confidence interval from -11.2 to 2.1). Three patients experienced virologic failure on darunavir/monotherapy and none on darunavir/r triple drug. No resistance to protease inhibitor emerged in patients with plasma viral load above 50 copies/ml. The two groups did not differ in the number of serious adverse events.
Darunavir/r monotherapy exhibited efficacy rate over 85% with concordant results in the magnitude of difference with darunavir/r triple drug regimen in both intent-to-treat and per protocol analyses, but discordant conclusions with respect to the noninferiority margin. Patients failing on darunavir/r monotherapy had no emergence of new darunavir resistance mutations preserving future treatment options.
达鲁那韦/利托那韦（达芦那韦/利托那韦）维持治疗策略，在 HIV RNA 病毒载量抑制的患者中，是一种避免核苷类似物毒性和降低成本的潜在长期策略。
MONOtherapy 抑制剂蛋白酶是一项前瞻性、开放性、非劣效性、96 周安全性和疗效试验，纳入了接受三联疗法治疗、病毒学抑制的患者，他们被随机分配到达芦那韦/利托那韦三联药物治疗方案或达芦那韦/利托那韦单药治疗。主要终点是第 48 周 HIV RNA 小于 400 拷贝/ml 的患者比例；治疗失败定义为两次连续 HIV RNA 大于 400 拷贝/ml（病毒学应答丧失时间）或任何治疗改变。该试验有 80%的效能显示单药治疗组非劣效性（delta =-10%，90%置信区间）。
共筛选了 242 例患者，其中 225 例被随机分配。在方案疗效分析中，达芦那韦/利托那韦三联药物治疗组的治疗成功率为 99%，达芦那韦/利托那韦单药治疗组为 94%（delta =-4.9%，90%置信区间，-9.1 至-0.8）。意向治疗人群也得到了类似的结果（92 例 vs 87.5%，delta =-4.5%，90%置信区间-11.2 至 2.1）。3 例患者在达芦那韦/单药治疗时出现病毒学失败，而达芦那韦/利托那韦三联药物治疗时没有。在病毒载量超过 50 拷贝/ml 的患者中，没有出现对蛋白酶抑制剂的耐药性。两组在严重不良事件的数量上没有差异。
达芦那韦/利托那韦单药治疗的疗效率超过 85%，在意向治疗和方案分析中，与达芦那韦/利托那韦三联药物治疗方案的差异幅度一致，但在非劣效性边界上的结论不一致。在达芦那韦/利托那韦单药治疗失败的患者中，没有出现新的达芦那韦耐药突变，保留了未来的治疗选择。
