Orrell Catherine, Felizarta Franco, Nell André, Kakuda Thomas N, Lavreys Ludo, Nijs Steven, Tambuyzer Lotke, Van Solingen-Ristea Rodica, Tomaka Frank L
Desmond Tutu HIV Foundation, UCT Medical School, P.O. Box 13801, Mowbray, Cape Town 7705, South Africa.
Private Practice, 3535 San Dimas Street, Suite 24, Bakersfield, CA 93301, USA.
AIDS Res Treat. 2015;2015:938628. doi: 10.1155/2015/938628. Epub 2015 Jan 15.
Objectives. TEACH (NCT00896051) was a randomized, open-label, two-arm Phase II trial to investigate the pharmacokinetic interaction between etravirine and atazanavir/ritonavir and safety and efficacy in treatment-experienced, HIV-1-infected patients. Methods. After a two-week lead-in of two nucleoside reverse transcriptase inhibitors (NRTIs) and atazanavir/ritonavir 300/100 mg, 44 patients received etravirine 200 mg bid with one NRTI, plus atazanavir/ritonavir 300/100 mg or 400/100 mg qd (n = 22 each group) over 48 weeks. Results. At steady-state etravirine with atazanavir/ritonavir 300/100 mg qd or 400/100 mg qd decreased atazanavir C min by 18% and 9%, respectively, with no change in AUC24 h or C max versus atazanavir/ritonavir 300/100 mg qd alone (Day -1). Etravirine AUC12 h was 24% higher and 16% lower with atazanavir/ritonavir 300/100 or 400/100 mg qd, respectively, versus historical controls. At Week 48, no significant differences were seen between the atazanavir/ritonavir groups in discontinuations due to adverse events (9.1% each group) and other safety parameters, the proportion of patients with viral load <50 copies/mL (intent-to-treat population, noncompleter = failure) (50.0%, atazanavir/ritonavir 300/100 mg qd versus 45.5%, 400/100 mg qd), and virologic failures (31.8% versus 27.3%, resp.). Conclusions. Etravirine 200 mg bid can be combined with atazanavir/ritonavir 300/100 mg qd and an NRTI in HIV-1-infected, treatment-experienced patients without dose adjustment.
目的。TEACH（NCT00896051）是一项随机、开放标签、双臂II期试验，旨在研究依曲韦林与阿扎那韦/利托那韦之间的药代动力学相互作用，以及在接受过治疗的HIV-1感染患者中的安全性和疗效。方法。在接受两种核苷类逆转录酶抑制剂（NRTIs）和300/100mg阿扎那韦/利托那韦导入治疗两周后，44例患者在48周内接受200mg依曲韦林每日两次，联合一种NRTI，加300/100mg或400/100mg阿扎那韦/利托那韦每日一次（每组n = 22）。结果。在稳态时，依曲韦林与300/100mg每日一次或400/100mg每日一次的阿扎那韦/利托那韦联合使用时，阿扎那韦的Cmin分别降低了18%和9%，与单独使用300/100mg每日一次的阿扎那韦/利托那韦相比（第-1天），AUC24h或Cmax无变化。与历史对照相比，依曲韦林的AUC12h在与300/100mg或400/100mg每日一次的阿扎那韦/利托那韦联合使用时分别高24%和低16%。在第48周时，阿扎那韦/利托那韦组之间在因不良事件停药（每组9.1%）和其他安全性参数、病毒载量<50拷贝/mL的患者比例（意向性治疗人群，未完成治疗者=治疗失败）（300/100mg每日一次的阿扎那韦/利托那韦组为50.0%，400/100mg每日一次的阿扎那韦/利托那韦组为45.5%）以及病毒学失败率（分别为31.8%和27.3%）方面均无显著差异。结论。在HIV-1感染、接受过治疗的患者中，200mg依曲韦林每日两次可与300/100mg每日一次的阿扎那韦/利托那韦及一种NRTI联合使用，无需调整剂量。
