TY - JOUR
T1 - The calculated genetic barrier for antiretroviral drug resistance substitutions is largely similar for different HIV-1 subtypes
AU - Van De Vijver, David A.
AU - Wensing, Annemarie M.J.
AU - Angarano, Gioacchino
AU - Åsjö, Birgitta
AU - Balotta, Claudia
AU - Boeri, Enzo
AU - Camacho, Ricardo
AU - Chaix, Marie Laure
AU - Costagliola, Dominique
AU - De Luca, Andrea
AU - Derdelinckx, Inge
AU - Grossman, Zehava
AU - Hamouda, Osamah
AU - Hatzakis, Angelos
AU - Hemmer, Robert
AU - Hoepelman, Andy
AU - Horban, Andrzej
AU - Korn, Klaus
AU - Kücherer, Claudia
AU - Leitner, Thomas
AU - Loveday, Clive
AU - MacRae, Eilidh
AU - Maljkovic, Irina
AU - De Mendoza, Carmen
AU - Meyer, Laurence
AU - Nielsen, Claus
AU - Op De Coul, Eline L.M.
AU - Ormaasen, Vidar
AU - Paraskevis, Dimitris
AU - Perrin, Luc
AU - Puchhammer-Stöckl, Elisabeth
AU - Ruiz, Lidia
AU - Salminen, Mika
AU - Schmit, Jean Claude
AU - Schneider, Francois
AU - Schuurman, Rob
AU - Soriano, Vincent
AU - Stanczak, Grzegorz
AU - Stanojevic, Maja
AU - Vandamme, Anne Mieke
AU - Van Laethem, Kristel
AU - Violin, Michela
AU - Wilbe, Karin
AU - Yerly, Sabine
AU - Zazzi, Maurizio
AU - Boucher, Charles A.B.
PY - 2006/3
Y1 - 2006/3
N2 - 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.
AB - 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.
KW - Drug resistance
KW - Genetic barrier
KW - HIV
KW - Non-B subtypes
UR - http://www.scopus.com/inward/record.url?scp=33645098601&partnerID=8YFLogxK
U2 - 10.1097/01.qai.0000209899.05126.e4
DO - 10.1097/01.qai.0000209899.05126.e4
M3 - Article
C2 - 16540937
AN - SCOPUS:33645098601
SN - 1525-4135
VL - 41
SP - 352
EP - 360
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 3
ER -