The calculated genetic barrier for antiretroviral drug resistance substitutions is largely similar for different HIV-1 subtypes

David A. Van De Vijver, Annemarie M.J. Wensing, Gioacchino Angarano, Birgitta Åsjö, Claudia Balotta, Enzo Boeri, Ricardo Camacho, Marie Laure Chaix, Dominique Costagliola, Andrea De Luca, Inge Derdelinckx, Zehava Grossman, Osamah Hamouda, Angelos Hatzakis, Robert Hemmer, Andy Hoepelman, Andrzej Horban, Klaus Korn, Claudia Kücherer, Thomas LeitnerClive Loveday, Eilidh MacRae, Irina Maljkovic, Carmen De Mendoza, Laurence Meyer, Claus Nielsen, Eline L.M. Op De Coul, Vidar Ormaasen, Dimitris Paraskevis, Luc Perrin, Elisabeth Puchhammer-Stöckl, Lidia Ruiz, Mika Salminen, Jean Claude Schmit, Francois Schneider, Rob Schuurman, Vincent Soriano, Grzegorz Stanczak, Maja Stanojevic, Anne Mieke Vandamme, Kristel Van Laethem, Michela Violin, Karin Wilbe, Sabine Yerly, Maurizio Zazzi, Charles A.B. Boucher*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

89 Citations (Scopus)


Background: The genetic barrier, defined as the number of mutations required to overcome drug-selective pressure, is an important factor for the development of HIV drug resistance. Because of high variability between subtypes, particular HIV-1 subtypes could have different genetic barriers for drug resistance substitutions. This study compared the genetic barrier between subtypes using some 2000 HIV-1 sequences (>600 of non-B subtype) isolated from antiretroviral-naive patients in Europe. Methods: The genetic barrier was calculated as the sum of transitions (scored as 1) and/or transversions (2.5) required for evolution to any major drug resistance substitution. In addition, the number of minor protease substitutions was determined for every subtype. Results: Few dissimilarities were found. An increased genetic barrier was calculated for I82A (subtypes C and G), V108I (subtype G), V118I (subtype G), Q151M (subtypes D and F), L210W (subtypes C, F, G, and CRF02_AG), and P225H (subtype A) (P < 0.001 compared with subtype B). A decreased genetic barrier was found for I82T (subtypes C and G) and V106M (subtype C) (P < 0.001 vs subtype B). Conversely, minor protease substitutions differed extensively between subtypes. Conclusions: Based on the calculated genetic barrier, the rate of drug resistance development may be similar for different HIV-1 subtypes. Because of differences in minor protease substitutions, protease inhibitor resistance could be enhanced in particular subtypes once the relevant major substitutions are selected.

Original languageEnglish
Pages (from-to)352-360
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Issue number3
Publication statusPublished - Mar 2006
Externally publishedYes


  • Drug resistance
  • Genetic barrier
  • HIV
  • Non-B subtypes


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