Clotet Bonaventura, Bellos Nicholas, Molina Jean-Michel, Cooper David, Goffard Jean-Christophe, Lazzarin Adriano, Wöhrmann Andrej, Katlama Christine, Wilkin Timothy, Haubrich Richard, Cohen Calvin, Farthing Charles, Jayaweera Dushyantha, Markowitz Martin, Ruane Peter, Spinosa-Guzman Sabrina, Lefebvre Eric
Hospital Universitari Germans Trias i Pujol and irsiCaixa Foundation, Ctra de Canyet s/n 08916, Barcelona, Catalonia, Spain.
Lancet. 2007 Apr 7;369(9568):1169-78. doi: 10.1016/S0140-6736(07)60497-8.
The continuing, randomised, multinational, phase IIB POWER 1 and 2 studies aim to evaluate efficacy and safety of darunavir in combination with low-dose ritonavir in treatment-experienced HIV-1-infected patients. We did a pooled subgroup analysis to update results at week 48 for patients receiving the recommended dose of darunavir-ritonavir compared with those receiving other protease inhibitors (PIs).
After 24-week dose-finding phases and primary efficacy analyses, patients randomised to receive darunavir-ritonavir were given 600/100 mg twice daily, and patients receiving control PIs continued on assigned treatment into the longer-term, open-label phase; all patients continued on optimised background regimen. We assessed patients who had reached week 48 or discontinued earlier at the time of analysis; for the darunavir-ritonavir group, only patients who received 600/100 mg twice daily from baseline were included. Analyses were intention-to-treat. The POWER 2 study (TMC114-C202) is registered with ClinicalTrials.gov (NCT00071097).
At week 48, 67 of 110 (61%) darunavir-ritonavir patients compared with 18 of 120 (15%) of control PI patients had viral load reductions of 1 log10 copies per mL or greater from baseline (primary endpoint; difference in response rates 46%, 95% CI 35%-57%, p<0.0001). Based on a logistic regression model including stratification factors (baseline number of primary PI mutations, use of enfuvirtide, baseline viral load) and study as covariates, the difference in response was 50% (odds ratio 11.72, 95% CI 5.75-23.89). In the darunavir-ritonavir group, rates of adverse events were mostly lower than or similar to those in the control group when corrected for treatment exposure. No unexpected safety concerns were identified.
Efficacy responses with darunavir-ritonavir 600/100 mg twice daily plus optimised background regimen were greater than those with control PI and were sustained to at least week 48, with favourable safety and tolerability in treatment-experienced patients. This regimen could expand the treatment options available for such patients.
持续进行的随机、多国IIB期POWER 1和2研究旨在评估达芦那韦联合低剂量利托那韦用于经治HIV-1感染患者的疗效和安全性。我们进行了一项汇总亚组分析，以更新接受推荐剂量达芦那韦-利托那韦的患者与接受其他蛋白酶抑制剂（PI）的患者在第48周时的结果。
在24周剂量探索阶段和主要疗效分析之后，随机接受达芦那韦-利托那韦的患者每天两次给予600/100mg，接受对照PI的患者继续接受指定治疗进入长期开放标签阶段；所有患者继续接受优化的背景治疗方案。我们评估了在分析时已达到第48周或更早停药的患者；对于达芦那韦-利托那韦组，仅纳入从基线开始每天两次接受600/100mg的患者。分析采用意向性治疗。POWER 2研究（TMC114-C202）已在ClinicalTrials.gov注册（NCT00071097）。
在第48周时，110例达芦那韦-利托那韦患者中有67例（61%）与120例对照PI患者中的18例（15%）相比，病毒载量较基线降低了1 log10拷贝/mL或更多（主要终点；缓解率差异46%，95%CI 35%-57%，p<0.0001）。基于包含分层因素（主要PI突变的基线数量、恩夫韦肽的使用、基线病毒载量）和研究作为协变量的逻辑回归模型，缓解差异为50%（优势比1I.72，95%CI 5.75-23.89）。在达芦那韦-利托那韦组中，校正治疗暴露后不良事件发生率大多低于或类似于对照组。未发现意外的安全问题。
每天两次服用600/100mg达芦那韦-利托那韦加优化背景治疗方案的疗效反应大于对照PI，且至少持续到第48周，在经治患者中具有良好的安全性和耐受性。该方案可扩大此类患者的治疗选择。
