Gutiérrez Félix, Rodríguez Juan Carlos, García Federico, Poveda Eva
Servicio de Enfermedades Infecciosas, Hospital General Universitario de Elche, Alicante, Departamento de Medicina, Universidad Miguel Hernández, Alicante, España.
Enferm Infecc Microbiol Clin. 2011 Dec;29 Suppl 5:45-50. doi: 10.1016/S0213-005X(11)70043-X.
Determination of HIV-1 tropism is mandatory before using CCR5 antagonists in clinical practice. One drug of this class, maraviroc, has been approved for the treatment of HIV infection. The phenotypic assay, TrofileTM, was clinically validated in the clinical development program of maraviroc and has been widely used to select candidates for maraviroc therapy. Phenotypic tests, however, have the disadvantage of being complex, are costly and time-consuming, and their accessibility is limited, which hampers their routine use in clinical diagnosis. Genotypic assays, based on sequencing the third hypervariable (V3 loop) of the viral gene env, interpreted according to various genotypic bioinformatic tools, such as geno2pheno and PSSM, are faster and cheaper than phenotypic assays, and are also more accessible. In retrospective analyses of the maraviroc pivotal trials, genotypic methods using either conventional ("bulk") or deep-sequencing technology predicted virologic response to maraviroc similarly to phenotypic assays and are now included within several European recommendations to guide the clinical use of CCR5 antagonists.
在临床实践中使用CCR5拮抗剂之前，必须确定HIV-1嗜性。该类药物中的一种，马拉维罗，已被批准用于治疗HIV感染。TrofileTM表型检测在马拉维罗的临床开发项目中得到了临床验证，并已广泛用于选择接受马拉维罗治疗的候选者。然而，表型检测具有操作复杂、成本高、耗时且可及性有限的缺点，这阻碍了它们在临床诊断中的常规使用。基于对病毒基因env的第三个高变区（V3环）进行测序的基因检测，根据各种基因生物信息学工具（如geno2pheno和PSSM）进行解读，比表型检测更快、更便宜，且更容易获得。在对马拉维罗关键试验的回顾性分析中，使用传统（“批量”）或深度测序技术的基因方法预测对马拉维罗的病毒学反应与表型检测相似，现在已被纳入多项欧洲指南中，以指导CCR5拮抗剂的临床使用。
