Dierynck Inge, De Meyer Sandra, Lathouwers Erkki, Vanden Abeele Carline, Van De Casteele Tom, Spinosa-Guzman Sabrina, de Béthune Marie-Pierre, Picchio Gaston
Tibotec BVBA, Mechelen, Belgium.
Antivir Ther. 2010;15(8):1161-9. doi: 10.3851/IMP1697.
The effect of HIV type-1 (HIV-1) subtype on in vitro susceptibility and virological response to darunavir (DRV) and lopinavir (LPV) was studied using a broad panel of primary isolates, and in recombinant clinical isolates from treatment-naive, HIV-1-infected patients in the Phase III trial, AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects (ARTEMIS).
Patients received DRV/ritonavir (DRV/r) 800/100 mg once daily (n=343) or LPV/ritonavir (LPV/r) 800/200 mg total daily dose (n=346), plus a fixed daily dose of emtricitabine and tenofovir disoproxil fumarate.
DRV demonstrated high antiviral activity against a broad panel of HIV-1 major group (M) and outlier group (O) primary isolates in peripheral blood mononuclear cells, with a median 50% effective concentration (EC(50)) of 0.52 nM. Most (61%) patients in ARTEMIS harboured HIV-1 subtype B; other prevalent subtypes were C (13%) and CRF01_AE (17%); 9% harboured other subtypes. Median EC(50) values (interquartile range) for DRV were 1.79 nM (1.3-2.6) for subtype B, 1.12 nM (0.8-1.4) for C and 1.27 nM (1.0-1.7) for CRF01_AE. Virological response to DRV/r (HIV-1 RNA<50 copies/ml [intent-to-treat, time-to-loss of virological response algorithm]) was 81%, 87% and 85% for patients with subtype B, C and CRF01_AE infections, respectively. Similar results were observed in the LPV/r treatment group.
In vitro susceptibility to DRV was comparable across HIV-1 subtypes in a broad panel of primary isolates and in recombinant clinical isolates. Once daily DRV/r 800/100 mg and LPV/r 800/200 mg were highly effective in ARTEMIS irrespective of the HIV-1 subtype studied, confirming their broad anti-HIV-1 activity.
使用一组广泛的原始分离株，以及来自初治HIV-1感染患者的重组临床分离株，在III期试验“初治受试者中TMC114抗逆转录病毒治疗研究”（ARTEMIS）中，研究了HIV-1（人类免疫缺陷病毒1型）亚型对达芦那韦（DRV）和洛匹那韦（LPV）体外敏感性及病毒学反应的影响。
患者接受每日一次800/100mg的DRV/利托那韦（DRV/r）（n = 343）或每日总剂量800/200mg的LPV/利托那韦（LPV/r）（n = 346），加固定剂量的恩曲他滨和替诺福韦酯富马酸盐。
DRV对外周血单核细胞中一组广泛的HIV-1主要组（M）和异常组（O）原始分离株显示出高抗病毒活性，50%有效浓度（EC50）中位数为0.52nM。ARTEMIS中大多数（61%）患者感染的是HIV-1 B亚型；其他流行亚型为C（13%）和CRF01_AE（17%）；9%患者感染的是其他亚型。DRV的EC50值中位数（四分位间距），B亚型为1.79nM（1.3 - 2.6），C亚型为1.12nM（0.8 - 1.4），CRF01_AE亚型为1.27nM（1.0 - 1.7）。B、C和CRF01_AE亚型感染患者对DRV/r的病毒学反应（HIV-1 RNA<50拷贝/ml[意向性治疗，病毒学反应丧失时间算法]）分别为81%、87%和85%。在LPV/r治疗组中观察到类似结果。
在一组广泛的原始分离株和重组临床分离株中，各HIV-1亚型对DRV的体外敏感性相当。在ARTEMIS中，无论研究的HIV-1亚型如何，每日一次800/100mg的DRV/r和800/200mg的LPV/r均非常有效，证实了它们广泛的抗HIV-1活性。
