Saint Camillus International University of Health Sciences, Rome, Italy.
National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy.
J Glob Antimicrob Resist. 2022 Sep;30:326-334. doi: 10.1016/j.jgar.2022.06.027. Epub 2022 Jul 3.
We evaluated virological response and resistance profiles in individuals who were virologically suppressed who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in real life.
Survival analysis was used to assess probability of virological rebound (VR). Cumulative major resistance mutations (MRM) and cumulative genotypic susceptibility score (cGSS) were evaluated before the switch.
Overall, 283 individuals virologically suppressed for a median (interquartile [IQR]) time of 7 (3-9) y were analyzed. Of these, 20.8% were in first-line treatment, 13.1% were highly treatment-experienced (HTE), and 8.5% had experienced previous integrase inhibitor (INI)-failures. Before the switch, nucleotide reverse transcriptase inhibitor NRTI MRM prevalence was 29% (M184V:13.8%; any thymidine analogue mutation: 14.1%; K65R: 0.7%; K70E 0.4%); only three (2.1%) individuals showed INI major resistance mutations (Y143C/H/R [n = 1]; Y143C [n = 1]; N155H [n = 1]), and 82.0% of individuals received fully active B/F/TAF. Ninety-six wk after switch, the probability of VR was 5%, with only 12 events of VR at a median (IQR) viremia level of 284 (187-980) copies/mL, mainly transient. No significant associations between virological outcomes and genotypic susceptibility to B/F/TAF were observed. People who experienced previous INI failures showed a significantly higher adjusted hazard ratio (AHR [95% CI]) to experience VR under B/F/TAF (3.9 [1.1-13.4], P = 0.031). This AHR increased in people who experienced INI failures and received partially active B/F/TAF (5.5 [1.4-21.1], P = 0.013).
Within 96 wk, a switch to B/F/TAF in individuals who were virologically suppressed ensured a very high rate of virological control in a clinical setting. Previous resistance alone did not affect B/F/TAF response. However, people who had previous INI failures were more prone to losing virological control under B/F/TAF.
我们评估了在真实世界中，那些已经病毒学抑制的个体转换为比克替拉韦/恩曲他滨/丙酚替诺福韦（B/F/TAF）后的病毒学应答和耐药情况。
采用生存分析评估病毒学反弹（VR）的概率。在转换前评估累积主要耐药突变（MRM）和累积基因型敏感性评分（cGSS）。
共分析了 283 例病毒学抑制中位（四分位距 [IQR]）时间为 7（3-9）年的个体。其中，20.8%的患者处于一线治疗，13.1%的患者为高度治疗经验（HTE），8.5%的患者曾经历过整合酶抑制剂（INI）失败。转换前，核苷酸逆转录酶抑制剂 NRTI MRM 发生率为 29%（M184V：13.8%；任何胸苷类似物突变：14.1%；K65R：0.7%；K70E：0.4%）；仅 3 例（2.1%）患者出现 INI 主要耐药突变（Y143C/H/R [n=1]；Y143C [n=1]；N155H [n=1]），且 82.0%的患者接受了完全有效的 B/F/TAF。转换后 96 周，VR 的概率为 5%，仅发生 12 例 VR 事件，中位（IQR）病毒载量为 284（187-980）拷贝/ml，主要为一过性。未观察到病毒学结局与 B/F/TAF 基因型敏感性之间存在显著相关性。曾经历 INI 失败的患者在 B/F/TAF 下发生 VR 的调整后危险比（AHR [95%CI]）显著更高（3.9 [1.1-13.4]，P=0.031）。在曾经历 INI 失败且接受部分有效 B/F/TAF 的患者中，该 AHR 更高（5.5 [1.4-21.1]，P=0.013）。
在 96 周内，病毒学抑制的个体转换为 B/F/TAF 可确保在临床环境中实现非常高的病毒学控制率。单独的耐药性并不能影响 B/F/TAF 的反应。然而，曾经历 INI 失败的患者在 B/F/TAF 下更容易失去病毒学控制。
