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Drugs. 2018 Jul;78(10):1013-1024. doi: 10.1007/s40265-018-0934-2.
Darunavir/cobicistat/emtricitabine/tenofovir AF (Symtuza) is the first protease inhibitor (PI)-based single-tablet regimen (STR) available for the treatment of adults and adolescents (aged ≥ 12 years) with HIV-1 infection. It combines the PI darunavir (which has a high genetic barrier to resistance) with the pharmacokinetic booster cobicistat and the nucleos(t)ide reverse transcriptase inhibitors emtricitabine and tenofovir alafenamide (tenofovir AF), the latter being associated with less off-target tenofovir exposure than its predecessor tenofovir disoproxil fumarate (tenofovir DF). Over 48 weeks in phase 3 trials, darunavir/cobicistat/emtricitabine/tenofovir AF was noninferior to darunavir/cobicistat plus emtricitabine/tenofovir DF in establishing virological suppression in antiretroviral therapy (ART)-naïve adults and, likewise, was noninferior to an ongoing boosted PI, emtricitabine plus tenofovir DF regimen in preventing virological rebound in virologically-suppressed, ART-experienced adults. Resistance did not emerge to the STR components, with the exception being an emtricitabine resistance-associated mutation (RAM) [M184I/V] in one of seven recipients who experienced virological failure (although M184V was a minority variant at screening in this patient). Darunavir/cobicistat/emtricitabine/tenofovir AF was generally well tolerated, with renal and bone profile improvements but less favourable effects on some lipids versus tenofovir DF-based regimens. Thus, although longer-term and cost-effectiveness data would be beneficial, darunavir/cobicistat/emtricitabine/tenofovir AF is a welcome addition to the STRs available for the treatment of adults and adolescents with HIV-1 infection, being the first to combine the high genetic resistance barrier of darunavir with the renal/bone profile of tenofovir AF, thus expanding the patient population for whom an STR may be suitable.
达芦那韦/考比司他/恩曲他滨/替诺福韦艾拉酚胺（Symtuza）是首款可供治疗人类免疫缺陷病毒 1 型（HIV-1）感染的成人和青少年（年龄≥12 岁）使用的基于蛋白酶抑制剂（PI）的单片复方制剂（STR）。它将具有高遗传耐药屏障的 PI 达芦那韦与药代动力学增强剂考比司他，以及核苷（酸）逆转录酶抑制剂恩曲他滨和替诺福韦艾拉酚胺（替诺福韦 AF）联合使用，后者与前体替诺福韦二磷酸酯（tenofovir DF）相比，与非靶位替诺福韦的暴露量更少。在 3 期临床试验中，48 周时，达芦那韦/考比司他/恩曲他滨/替诺福韦 AF 在初治成人中与达芦那韦/考比司他加恩曲他滨/替诺福韦 DF 相比，在建立病毒学抑制方面非劣效，同样，在预防病毒学抑制、接受过 ART 的成人中出现病毒学反弹方面，与正在进行的增效 PI、恩曲他滨加替诺福韦 DF 方案相比非劣效。除了在 7 名发生病毒学失败的患者中有一名患者出现恩曲他滨耐药相关突变（RAM）[M184I/V]（尽管在该患者中筛查时 M184V 是少数变异）外，STR 成分未出现耐药。达芦那韦/考比司他/恩曲他滨/替诺福韦 AF 通常具有良好的耐受性，可改善肾功能和骨骼参数，但与基于替诺福韦 DF 的方案相比，对某些脂质的影响较差。因此，虽然长期和成本效益数据将是有益的，但达芦那韦/考比司他/恩曲他滨/替诺福韦 AF 是可供治疗 HIV-1 感染的成人和青少年使用的 STR 的一大补充，它是首款将达芦那韦的高遗传耐药屏障与替诺福韦 AF 的肾功能/骨骼参数结合的药物，从而扩大了适合使用 STR 的患者群体。
