Gilead Sciences, Foster City, CA.
J Acquir Immune Defic Syndr. 2020 Nov 1;85(3):363-371. doi: 10.1097/QAI.0000000000002454.
Study 4030 was a phase 3, randomized, double-blinded study of 565 HIV-1 RNA-suppressed participants switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir (DTG)+F/TAF. Nucleoside reverse transcriptase inhibitor (NRTI), non-NRTI, and protease inhibitor resistance (-R) was allowed, but integrase strand transfer inhibitor-R was excluded. Here, we describe the detailed resistance analysis.
Historical plasma HIV-1 RNA genotypes and baseline proviral DNA genotypes were analyzed. Documented or investigator-suspected NRTI-R was grouped for stratification into 3 categories of level of resistance. Viral blips were assessed through week 48. Virologic failures had genotypic and phenotypic resistance analyses at week 48, confirmed failure, or last visit, if HIV-1 RNA did not resuppress to <50 copies/mL while on study drug.
In total, 83% (470/565) of participants had baseline genotypic data available with NRTI-R detected in 24% (138/565), including 5% (30/565) with K65R/E/N or ≥3 thymidine analog mutations and 19% (108/565) with other NRTI-R mutations. M184V/I was present in 14% (81/565). Pre-existing integrase strand transfer inhibitor-R mutations were found in 4% (20/565) of participants. Primary non-NRTI-R and protease inhibitor-R mutations were present in 21% (118/565) and 7% (38/565) of participants. High rates of viral suppression were maintained in all groups through week 48; blips were observed in only 15 participants (2.7%). Three participants met criteria for resistance analysis (all in DTG+F/TAF arm); none developed treatment-emergent resistance to study drugs.
Participants with baseline NRTI resistance, much of which was previously undocumented, maintained suppression 48 weeks after switching to B/F/TAF or DTG+F/TAF triple therapy. Blips and virologic failure were uncommon using either regimen, with no treatment-emergent resistance.
研究 4030 是一项 3 期、随机、双盲研究，共纳入 565 名 HIV-1 RNA 抑制的参与者，他们转换为比替拉韦/恩曲他滨/替诺福韦艾拉酚胺（B/F/TAF）或多替拉韦（DTG）+F/TAF。允许存在核苷逆转录酶抑制剂（NRTI）、非核苷逆转录酶抑制剂和蛋白酶抑制剂耐药（-R），但排除整合酶抑制剂耐药（-R）。在此，我们描述了详细的耐药分析。
分析了历史血浆 HIV-1 RNA 基因型和基线前病毒 DNA 基因型。将有记录或研究者怀疑的 NRTI-R 分组为 3 个耐药水平类别。通过第 48 周评估病毒学突破。如果在研究药物治疗期间 HIV-1 RNA 未抑制到<50 拷贝/mL，则在第 48 周发生病毒学失败的患者进行基因型和表型耐药分析，确认失败或最后一次就诊。
共有 83%（565 名中的 470 名）的参与者具有基线基因型数据，其中 24%（565 名中的 138 名）检测到 NRTI-R，包括 5%（565 名中的 30 名）有 K65R/E/N 或≥3 胸腺嘧啶类似物突变和 19%（565 名中的 108 名）有其他 NRTI-R 突变。M184V/I 存在于 14%（565 名中的 81 名）的参与者中。4%（565 名中的 20 名）的参与者存在原发性整合酶抑制剂耐药突变。主要非核苷逆转录酶抑制剂和蛋白酶抑制剂耐药突变分别存在于 21%（565 名中的 118 名）和 7%（565 名中的 38 名）的参与者中。所有组在第 48 周均维持了较高的病毒抑制率；仅 15 名参与者（2.7%）出现病毒学突破。3 名参与者符合耐药分析标准（均在 DTG+F/TAF 组）；没有参与者对研究药物产生治疗后耐药。
基线时存在 NRTI 耐药的参与者，其中大部分以前未记录在案，在转换为 B/F/TAF 或 DTG+F/TAF 三联疗法后 48 周仍保持抑制。两种方案的病毒学突破和病毒学失败都很少见，没有治疗后耐药。
