@article{3098985,
    title = "The calculated genetic barrier for antiretroviral drug resistance
substitutions is largely similar for different HIV-1 subtypes",
    author = "van de Vijver, DA and Wensing, AMJ and Angarano, G and Asjo, B and and Balotta, C and Boeri, E and Camacho, R and Chaix, ML and Costagliola, D and and De Luca, A and Derdelinckx, I and Grossman, Z and Hamouda, O and and Hatzakis, A and Hemmer, R and Hoepelman, A and Horban, A and Korn, K and and Kucherer, C and Leitner, T and Loveday, C and MacRae, E and Maljkovic, I and and de Mendoza, C and Meyer, L and Nielsen, C and de Coul, ELMO and and Ormaasen, V and Paraskevis, D and Perrin, L and Puchhammer-Stockl, E and and Ruiz, L and Salminen, M and Schmit, JC and Schneider, F and Schuurman, R and and Soriano, V and Stanczak, G and Stanojevic, M and Vandamme, AM and and Van Laethem, K and Violin, M and Wilbe, K and Yerly, S and Zazzi, M and and Boucher, CAB and SPREAD Programme",
    journal = "JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES",
    year = "2006",
    volume = "41",
    number = "3",
    pages = "352-360",
    publisher = "Lippincott, Williams & Wilkins",
    doi = "10.1097/01.qai.0000209899.05126.e4",
    keywords = "HIV; non-B subtypes; drug resistance; genetic barrier",
    abstract = "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 182A (subtypes C and G), V 1081 (subtype G), V 1181
(subtype G), Q 15 1 M (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."
}