Genotypic Determination of HIV Tropism – Clinical and Methodological Recommendations to Guide the Therapeutic Use of CCR5 Antagonists
Eva Poveda 1, José Alcamí 2, Roger Paredes 1, Juan Córdoba 1, Félix Gutiérrez 1, Josep M. Llibre 1, Rafael Delgado 1, Federico Pulido 1, José Hernández Quero 1, Miguel GarcÃa-Deltoro , José Antonio Iribarren 1, Santiago Moreno 1, Federico García 1
1 NULL; 2 AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid; HIV Unit, Hospital Clínic de Barcelona, IDIBAPS, Barcelona; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid. Spain
*Correspondence: Eva Poveda, Email not available
Abstract
The approval of maraviroc (Selzentri®), the first CCR5 antagonist, with specific antiviral activity against CCR5 (R5)-tropic HIV variants, has promoted the determination of HIV coreceptor usage in the clinical setting. The phenotypic assay TrofileTM, which is based on recombinant virus technology, has been the most widely used diagnostic test, given that it was the only assay which provided tropism information in the pivotal maraviroc clinical trials. However, this method displays logistical and technical limitations that make it far from convenient as a diagnostic test in clinical practice. Genotypic methods based on V3 genotyping represent a more feasible alternative and progressively are replacing phenotypic assays. Even though their sensitivity to detect X4-tropic variants is lower compared to TrofileTM, recent studies have demonstrated that specific genotypic tools (geno2pheno and PSSM) are comparable to TrofileTM and ES-TrofileTM in predicting virologic response to maraviroc. This review summarizes clinical and methodological recommendations for the genotypic determination of HIV tropism to guide therapeutic decisions with CCR5 antagonists in HIV therapeutics.
