Effect of human immunodeficiency virus type 1 protease inhibitor therapy and subtype on development of resistance in subtypes B and G

Ana Carolina Palma, Ana Barroso Abecasis, Jurgen Vercauteren, Ana P. Carvalho, Joaquim Cabanas, Anne-Mieke Vandamme, Ricardo Jorge Camacho

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Europe is currently observing a significant rise in non-B subtypes. Consequently, the effect of genetic variability on therapy response or genotypic resistance interpretation algorithms is an emerging concern. The purpose of this study is to investigate the amino acid substitutions selected under drug pressure in the protease of human immunodeficiency virus type 1 (HIV-1) subtypes B and G, and determine if there are any significant differences. We investigated therapy-related and subtype-related substitutions in the protease, considering subtype, overall protease inhibitor treatment and individual drug exposure. Many mutations were significantly related to protease inhibitor (PI) therapy, with mutations exclusive to subtype B or subtype G. Some mutations are at positions related to resistance in both subtypes, but the amino acid substitution is different. Other mutations were significantly associated with subtype and PI selective pressure (p<0.05), pointing towards a differential selective pressure in both subtypes. We confirmed previous reports on the subtype-dependent selection of D30N and 89I, and identified a new mutation with such differential selective pressure: 37D was preferentially selected by lopinavir in subtype B. Other novel mutations found under therapy pressure were 13A, 35N, K55R, I66F, I72L/T, T74S, 82M and 89I/V. Our study indicates that even though in general, drug selective pressure and resistance pathways are relatively similar between subtypes B and G, some differences do occur, leading to subtype-dependent substitutions.

Original languageEnglish
Pages (from-to)373-379
Number of pages6
JournalInfection Genetics And Evolution
Volume10
Issue number3
DOIs
Publication statusPublished - Apr 2010

Keywords

  • Amino Acid Substitution
  • Drug Resistance, Viral
  • Genetic Variation
  • HIV Infections
  • HIV Protease
  • HIV Protease Inhibitors
  • HIV-1
  • Humans
  • Indinavir
  • Lopinavir
  • Phylogeny
  • Pyrimidinones
  • Selection, Genetic
  • Sequence Analysis, Protein
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't

UN Sustainable Development Goals (SDGs)

  • SDG 3 - Good Health and Well-Being

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