Lathouwers Erkki, Wong Eric Y, Luo Donghan, Seyedkazemi Sareh, De Meyer Sandra, Brown Kimberley
a Janssen Infectious Diseases BVBA , Beerse , Belgium.
b Janssen Scientific Affairs, LLC , Titusville , NJ , USA.
HIV Clin Trials. 2017 Nov-Dec;18(5-6):196-204. doi: 10.1080/15284336.2017.1387690. Epub 2017 Nov 16.
Darunavir 800 mg once daily (QD) is indicated for HIV-1-infected treatment-naïve and treatment-experienced (without darunavir resistance-associated mutations [RAMs]) individuals, and has been evaluated in phase 2/3 studies with durations between 48 and 192 weeks.
To summarize the development (or identification) of post-baseline resistance (RAMs and antiretroviral phenotypic susceptibility) among patients receiving darunavir QD dosing.
Seven phase 2/3 studies with available genotypes/phenotypes for subjects treated with ritonavir- or cobicistat-boosted darunavir 800 mg QD regimens were assessed: ARTEMIS (NCT00258557; n = 343), GS-US-299-0102 (NCT01565850; n = 153), GS-US-216-0130 (NCT01440569; n = 313), ODIN (NCT00524368; n = 294), INROADS (NCT01199939; n = 54), MONET (NCT00458302; n = 256), and PROTEA (NCT01448707; n = 273). Genotypic analyses were conducted at baseline (except switch studies enrolling virologically suppressed subjects [MONET, PROTEA]). Criteria for post-baseline resistance testing and evaluation of the development (or identification [switch studies]) of RAMs (respective IAS-USA mutations) varied slightly across studies.
Among 1686 subjects treated with darunavir 800 mg QD regimens, 184 had protocol-defined virologic failure; 182 had post-baseline genotypes analyzed. Overall, 4/1686 (0.2%) developed (or had identified [switch studies]) primary protease inhibitor and/or darunavir RAMs (ARTEMIS, n = 1; GS-US-216-0130, n = 1; ODIN, n = 1; MONET, n = 1). Only 1/1686 (<0.1%) subject lost darunavir phenotypic susceptibility (ODIN; possibly related to prior ritonavir-boosted lopinavir virologic failure). Among 1103 subjects using a nucleos(t)ide reverse transcriptase inhibitor (N[t]RTI) backbone, 10 (0.9%) developed ≥ 1 N(t)RTI RAM (8 had the emtricitabine RAM M184I/V).
Darunavir has a high genetic barrier to resistance. Across a diverse population of HIV-1-infected subjects treated with darunavir 800 mg QD regimens, the development of darunavir resistance was rare (<0.1%).
每日一次（QD）服用800毫克达芦那韦适用于初治和经治（无达芦那韦耐药相关突变[RAMs]）的HIV-1感染个体，并且已在2/3期研究中进行了评估，研究持续时间为48至192周。
总结接受每日一次达芦那韦给药的患者基线后耐药性（RAMs和抗逆转录病毒表型敏感性）的发展（或识别情况）。
评估了7项2/3期研究，这些研究提供了接受利托那韦或考比司他增强的每日一次800毫克达芦那韦方案治疗的受试者的基因型/表型：ARTEMIS（NCT00258557；n = 343）、GS-US-299-0102（NCT01565850；n = 153）、GS-US-216-0130（NCT01440569；n = 313）、ODIN（NCT00524368；n = 294）、INROADS（NCT01199939；n = 54）、MONET（NCT00458302；n = 256）和PROTEA（NCT01448707；n = 273）。在基线时进行了基因分析（招募病毒学抑制受试者的转换研究[MONET、PROTEA]除外）。各研究中，基线后耐药性检测标准以及RAMs（各自的IAS-USA突变）发展（或识别[转换研究]）的评估标准略有不同。
在1686例接受每日一次800毫克达芦那韦方案治疗的受试者中，184例出现方案定义的病毒学失败；182例进行了基线后基因型分析。总体而言，4/1686（0.2%）出现（或识别出[转换研究]）原发性蛋白酶抑制剂和/或达芦那韦RAMs（ARTEMIS，n = 1；GS-US-216-0130，n = 1；ODIN，n = 1；MONET，n = 1）。仅1/1686（<0.1%）的受试者失去了达芦那韦表型敏感性（ODIN；可能与先前利托那韦增强的洛匹那韦病毒学失败有关）。在1103例使用核苷类逆转录酶抑制剂（N[t]RTI）主干方案的受试者中，10例（0.9%）出现≥一种N[t]RTI RAM（8例具有恩曲他滨RAM M184I/V）。
达芦那韦具有较高的耐药基因屏障。在接受每日一次800毫克达芦那韦方案治疗的不同HIV-1感染人群中，达芦那韦耐药的发生很罕见（<0.1%）。
