Background: 

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.

Methods: 

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.

Results: 

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.

Conclusions: 

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.

中文翻译：

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在已存在NRTI耐药的情况下从Dolutegravir（DTG）+ F / TAF或DTG + F / Tenofovir Disoproxil Fumarate（TDF）切换至Bictegravir / Emtricitabine / Tenofovir Alafenamide（B / F / TAF）

背景： 

研究4030是一项3期，随机，双盲研究，研究了565个HIV-1 RNA抑制的参与者，他们改用比格列韦/恩曲他滨/替诺福韦alafenamide（B / F / TAF）或多洛格韦（DTG）+ F / TAF。允许使用核苷逆转录酶抑制剂（NRTI），非NRTI和蛋白酶抑制剂抗性（-R），但排除整合酶链转移抑制剂-R。在这里，我们描述了详细的电阻分析。

方法： 

分析了历史血浆HIV-1 RNA基因型和基线原病毒DNA基因型。有文件记录或经研究人员怀疑的NRTI-R被分为三个等级的抵抗力等级。在第48周评估病毒斑点。在研究药物治疗期间，如果HIV-1 RNA不能重新抑制至<50拷贝/ mL，则病毒学失败应在第48周进行基因型和表型耐药性分析，确认失败或最后一次就诊。

结果： 

共有83％（470/565）的参与者具有基线基因型数据，其中24％（138/565）中检测到NRTI-R，包括5％（30/565）的K65R / E / N或≥3胸苷类似物突变和其他NRTI-R突变的19％（108/565）。M184V / I的含量为14％（81/565）。在4％（20/565）的参与者中发现了预先存在的整合酶链转移抑制剂R突变。21％（118/565）和7％（38/565）的参与者中存在主要的非NRTI-R和蛋白酶抑制剂R突变。到第48周，所有组的病毒抑制率均保持较高；仅15位参与者（2.7％）观察到斑点。三名参与者符合耐药性分析标准（全部在DTG + F / TAF组中）；没有人对研究药物产生治疗紧急反应。

结论： 

基线NRTI耐药的参与者（其中许多以前以前没有记录）在转为B / F / TAF或DTG + F / TAF三联疗法后48周仍保持抑制。两种治疗方案均不易出现唇疱疹和病毒学衰竭，且无治疗新药耐药。