第 48 周分析每日一次与每日两次使用达芦那韦/利托那韦治疗经治 HIV-1 感染患者的疗效。

Week 48 analysis of once-daily vs. twice-daily darunavir/ritonavir in treatment-experienced HIV-1-infected patients.

机构信息

Fundación Huesped, Buenos Aires, Argentina.

出版信息

AIDS. 2011 Apr 24;25(7):929-39. doi: 10.1097/QAD.0b013e328345ee95.

DOI:10.1097/QAD.0b013e328345ee95

PMID:21346512

Abstract

OBJECTIVE

ODIN (Once-daily Darunavir In treatment-experieNced patients) was a phase III, 48-week, open-label study comparing once-daily vs. twice-daily darunavir/ritonavir (DRV/r) in treatment-experienced patients with no DRV resistance-associated mutations (RAMs) at screening.

METHODS

Patients with no DRV RAMs and receiving stable HAART for at least 12 weeks were stratified by HIV-1 RNA (≤ or > 50 000 copies/ml) and randomized to once-daily DRV/r 800/100 mg or twice-daily DRV/r 600/100 mg and an optimized background regimen (≥2 nucleoside reverse transcriptase inhibitors). Primary objective was to demonstrate noninferiority of once-daily vs. twice-daily DRV/r in confirmed virologic response (HIV-1 RNA < 50 copies/ml) at week 48.

RESULTS

Five hundred and ninety patients received once-daily (n = 294) or twice-daily (n = 296) DRV/r. Mean baseline HIV-1 RNA was 4.16 log10 copies/ml; median CD4 cell count was 228 cells/μl; and 53.9% had previously used at least one protease inhibitor. At week 48, 72.1% of once-daily and 70.9% of twice-daily patients achieved HIV-1 RNA less than 50 copies/ml (intent-to-treat/time-to-loss of virologic response). The difference in response between once-daily and twice-daily arms was 1.2% (95% confidence interval -6.1 to 8.5%; P < 0.001), establishing noninferiority of once-daily DRV/r versus twice-daily DRV/r. Median CD4 cell count increase was 100 (once-daily) and 94 cells/μl (twice-daily). Virologic failure rate was low and similar for both arms; only one patient (once-daily arm) developed primary protease inhibitor mutations. Once-daily DRV/r had a lower incidence of grade 2-4 triglyceride increases (5.2 vs. 11.0%, P < 0.05).

CONCLUSION

Once-daily DRV/r 800/100 mg was noninferior in virologic response to twice-daily DRV/r 600/100 mg at 48 weeks in treatment-experienced patients with no DRV RAMs, and with a more favorable lipid profile. These findings support use of once-daily DRV/r in this population.

摘要

目的

ODIN（每日一次达芦那韦治疗经验患者）是一项为期 48 周、开放标签的 III 期研究，比较了无达芦那韦耐药相关突变（RAM）的治疗经验患者中每日一次与每日两次达芦那韦/利托那韦（DRV/r）的疗效。

方法

无 DRV RAM 且接受稳定的高效抗逆转录病毒治疗（HAART）至少 12 周的患者按 HIV-1 RNA（≤或>50000 拷贝/ml）分层，并随机分为每日一次 DRV/r800/100mg 或每日两次 DRV/r600/100mg 联合优化背景治疗方案（≥2 种核苷逆转录酶抑制剂）。主要目的是证明每日一次与每日两次 DRV/r 在第 48 周时确认的病毒学应答（HIV-1 RNA<50 拷贝/ml）方面具有非劣效性。

结果

590 例患者接受了每日一次（n=294）或每日两次（n=296）DRV/r 治疗。平均基线 HIV-1 RNA 为 4.16log10 拷贝/ml；中位 CD4 细胞计数为 228 个/μl；53.9%曾至少使用过一种蛋白酶抑制剂。第 48 周时，72.1%的每日一次组和 70.9%的每日两次组达到 HIV-1 RNA<50 拷贝/ml（意向治疗/病毒学应答丧失时间）。每日一次组和每日两次组之间的反应差异为 1.2%（95%置信区间-6.1 至 8.5%；P<0.001），证实了每日一次 DRV/r 与每日两次 DRV/r 的非劣效性。中位 CD4 细胞计数增加了 100（每日一次）和 94 个/μl（每日两次）。两种方案的病毒学失败率均较低且相似；只有 1 例患者（每日一次组）出现了原发性蛋白酶抑制剂突变。每日一次 DRV/r 的 2-4 级甘油三酯升高发生率较低（5.2%与 11.0%，P<0.05）。