title: Naturally occurring resistance mutations to HIV-1 entry inhibitors in subtypes B, C, and CRF31_BC.
abstract: BACKGROUND
  Entry inhibitors are a class of antiretroviral (ARV) drugs that prevent HIV replication by blocking viral entry into the host cell. The investigation of naturally occurring mutations associated with entry inhibitors across subtypes is required because genetic differences between HIV-1 variants may influence the emergence of drug resistance. Despite the importance of subtype C, which predominates globally, the majority of studies include only subtype B strains.
  
  
  OBJECTIVE
  To investigate the presence of natural resistance mutations to entry inhibitors in HIV-1 subtypes B, C, and CRF31_BC strains.
  
  
  METHODS
  Eighty samples were collected from antiretroviral-naïve patients. The gp41 gene from 67 patients and the gp120 gene from 65 patients were partially sequenced. Resistance mutations to entry inhibitors Enfuvirtide, Maraviroc, and Vicriviroc were screened.
  
  
  RESULTS
  ENF resistance-associated mutations of HR1 and HR2 on gp41 were not associated with any subtype. However, the major polymorphisms detected in HR1: N42S, L54M, and A67T were most prevalent in subtype C (p<0.001). Mutations A316T and R315Q in gp120, which are related to MVC and VCV reduced susceptibility respectively, were predominant in subtype C (p<0.05).
  
  
  CONCLUSIONS
  This study shows that many more resistance-associated mutations to entry inhibitors in ARV-naïve patients occur in subtype C compared with subtype B strains. However, further studies will be necessary to elucidate if the differential genetic background of HIV subtypes can affect the efficacy of treatment with entry inhibitors.
authors.affiliation: Centro de Desenvolvimento Científico e Tecnológico (CDCT), Fundação Estadual de Produção e Pesquisa em Saúde (FEPPS), Porto Alegre, Brazil. leonardo luvison@hotmail.com
authors.forename: Leonardo Augusto Luvison
authors.initials: LA
authors.lastname: Araújo
authors.forename: Dennis Maletich
authors.initials: DM
authors.lastname: Junqueira
authors.forename: Rubia Marília
authors.initials: RM
authors.lastname: de Medeiros
authors.forename: Maria Cristina Cotta
authors.initials: MC
authors.lastname: Matte
authors.forename: Sabrina Esteves de Matos
authors.initials: SE
authors.lastname: Almeida
mesh_terms: D019943:Amino Acid Substitution; D024882:Drug Resistance, Viral; D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015700:HIV Envelope Protein gp41 / Q000235:genetics; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA
chemical_list: D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; C514793:gp120 protein, Human immunodeficiency virus 1; C514787:gp41 protein, Human immunodeficiency virus 1