title: HIV-1 dynamics and coreceptor usage in Maraviroc-treated patients with ongoing replication.
abstract: There is evidence that HIV-1 evolution under maraviroc (MVC) pressure can lead to the selection of either X4-tropic variants and/or R5-tropic, MVC-resistant isolates. However, the viral dynamics of HIV-1 variants in patients with virological failure (VF) on MVC-containing regimens remain poorly studied. Here, we investigated the V3 loop evolution of HIV-1 on MVC in relation to coreceptor usage and the nature of HIV-1 quasispecies before MVC therapy using bulk population sequences and ultradeep sequencing. The majority of patients had no detectable minority X4 variant at baseline. The evolution of tropism was followed up until VF and showed three possibilities for viral evolution in these patients: emergence of preexisting X4 variants, de novo selection of R5 variants presenting V3 loop mutations, or replication of R5 variants without selection of known mutations.
authors.affiliation: Laboratoire de Virologie, CHU de Bordeaux and MFP-UMR5234, Universite Bordeaux 2, Bordeaux, France.
authors.forename: P
authors.initials: P
authors.lastname: Recordon-Pinson
authors.forename: S
authors.initials: S
authors.lastname: Raymond
authors.forename: P
authors.initials: P
authors.lastname: Bellecave
authors.forename: A G
authors.initials: AG
authors.lastname: Marcelin
authors.forename: C
authors.initials: C
authors.lastname: Soulie
authors.forename: D
authors.initials: D
authors.lastname: Descamps
authors.forename: V
authors.initials: V
authors.lastname: Calvez
authors.forename: P R
authors.initials: PR
authors.lastname: Harrigan
authors.forename: H
authors.initials: H
authors.lastname: Fleury
authors.forename: J
authors.initials: J
authors.lastname: Izopet
authors.forename: B
authors.initials: B
authors.lastname: Masquelier
mesh_terms: D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D019143:Evolution, Molecular; D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D023581:HIV Fusion Inhibitors / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D000077592:Maraviroc; D010446:Peptide Fragments / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics* / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D012641:Selection, Genetic; D017423:Sequence Analysis, RNA; D014230:Triazoles / Q000627:therapeutic use*; D056189:Viral Tropism
chemical_list: D065100:CCR5 Receptor Antagonists; C527276:CXCR4 protein, human; D003510:Cyclohexanes; D015699:HIV Envelope Protein gp120; D023581:HIV Fusion Inhibitors; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014230:Triazoles; D000077592:Maraviroc