来自O组的遗传上不同的HIV-1株(HIV-1非M)的易感性,N,和P到CCR5共受体拮抗剂,maraviroc(MVC),在45个临床菌株的大小组中进行了调查,病毒遗传多样性的代表。将结果与具有已知向性的HIV-1组M(HIV-1/M)的参考菌株进行比较。在非M菌株中,观察到对MVC的广泛表型敏感性。绝大多数HIV-1/O毒株(40/42)对MVC表现出很高的易感性,中值和平均IC50值为1.23和1.33nM,分别,与HIV-1/MR5株(1.89nM)相似。然而,剩下的两个HIV-1/O菌株表现出较低的易感性(IC50在482和496nM),根据他们的双重/混合(DM)取向。有趣的是,两种HIV-1/N菌株表现出不同的易感性模式,尽管总是具有相对较低的IC50值(2.87和47.5nM)。这强调了仅基于IC50值确定敏感性的复杂性。我们的研究检查了所有HIV-1非M组对MVC的易感性,并将这些发现与病毒嗜性(X4,R5或DM)相关联。结果证实了在感染HIV-1非M的患者开始MVC治疗之前确定向性的重要意义。此外,我们主张考虑额外的参数,例如抑制曲线的斜率,提供更全面的表型易感性特征。
目的:与HIV-1M组不同,缺乏对HIV-1非M群体的研究(O,N,和P)在理解他们对抗逆转录病毒治疗的易感性方面提出了挑战,特别是由于它们对非核苷逆转录酶抑制剂的天然抗性。TROPI-CO研究在逻辑上补充了我们先前对整合酶抑制剂和抗gp120功效的研究。迄今为止存在的45种非M菌株的最大组产生了关于maraviroc(MVC)易感性的有价值的结果。MVCIC50的显著变化揭示了一系列的磁化率,大多数菌株表现出R5向性。值得注意的是,无MVC耐药菌株提示潜在的治疗途径.该研究还采用了强大的基于细胞的新型表型测定,并根据抑制曲线斜率确定了不同的磁化率。我们的发现强调了在启动MVC之前确定向性的重要性,并为在HIV-1非M感染的微妙背景下选择有效的治疗策略提供了重要的见解。
The susceptibility of genetically divergent HIV-1 strains (HIV-1 non-M) from groups O, N, and P to the CCR5 co-receptor antagonist, maraviroc (MVC), was investigated among a large panel of 45 clinical strains, representative of the viral genetic diversity. The results were compared to the reference strains of HIV-1 group M (HIV-1/M) with known tropism. Among the non-M strains, a wide range of phenotypic susceptibilities to MVC were observed. The large majority of HIV-1/O strains (40/42) displayed a high susceptibility to MVC, with median and mean IC50 values of 1.23 and 1.33 nM, respectively, similar to the HIV-1/M R5 strain (1.89 nM). However, the two remaining HIV-1/O strains exhibited a lower susceptibility (IC50 at 482 and 496 nM), in accordance with their dual/mixed (DM) tropism. Interestingly, the two HIV-1/N strains demonstrated varying susceptibility patterns, despite always having relatively low IC50 values (2.87 and 47.5 nM). This emphasized the complexity of determining susceptibility solely based on IC50 values. Our
study examined the susceptibility of all HIV-1 non-M groups to MVC and correlated these findings with virus tropism (X4, R5, or DM). The results confirm the critical significance of tropism determination before initiating MVC treatment in patients infected with HIV-1 non-M. Furthermore, we advocate for the consideration of additional parameters, such as the slope of inhibition curves, to provide a more thorough characterization of phenotypic susceptibility profiles.
OBJECTIVE: Unlike HIV-1 group M, the scarcity of studies on HIV-1 non-M groups (O, N, and P) presents challenges in understanding their susceptibility to antiretroviral treatments, particularly due to their natural resistance to non-nucleoside reverse transcriptase inhibitors. The TROPI-CO
study logically complements our prior investigations into integrase inhibitors and anti-gp120 efficacy. The largest panel of 45 non-M strains existing so far yielded valuable results on maraviroc (MVC) susceptibility. The significant variations in MVC IC50 reveal a spectrum of susceptibilities, with most strains displaying R5 tropism. Notably, the absence of MVC-resistant strains suggests a potential therapeutic avenue. The
study also employs a robust novel cell-based phenotropism assay and identifies distinct groups of susceptibilities based on inhibition curve slopes. Our findings emphasize the importance of determining tropism before initiating MVC and provide crucial insights for selecting effective therapeutic strategies in the delicate context of HIV-1 non-M infections.