The calculated genetic barrier for antiretroviral drug resistance substitutions is largely similar for different HIV-1 subtypes
Vijver, D.A. van de; Wensing, A.M.J.; Angarano, G.; Asjo, B.; Balotta, C.; Camacho, R.; Chaix, M.; Costagliola, D.; De Luca, A.; Derdelinckx, I.; Grossman, Z.; Hamouda, O.; Hatzakis, A.; Hemmer, R.; Hoepelman, A.I.M.; Horban, A.; Korn, K.; Kücherer, C.; Leitner, T.; Loveday, C.; MacRae, E.; Maljkovic, I.; Mendoza, C. de; Meyer, L.; Nielsen, C.; Op de Coul, E.L.M.; Omaasen, V.; Paraskevis, D.; Perrin, L.; Puchhammer-Stöckl, E.; Salminen, M.; Schmit, J.; Scheider, F.; Schuurman, R.; Soriano, V.; Stanczak, G.; Stanojevic, M.; Vandamme, A.; Laethem, K. van; Violin, M.; Wilde, K.; Yerly, S.; Zazzi, M.; Boucher, C.A.B.
(2006) Journal of Acquired Immune Deficiency Syndromes, volume 41, issue 3, pp. 352 - 360
(Article)
Abstract
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
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(9600 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 G 0.001
compared with subtype B). A decreased genetic barrier was found
for I82T (subtypes C and G) and V106M (subtype C) (P G 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.
Key Words: HIV, non-B subtypes, drug resistance, genetic barrier
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Keywords: HIV, non-B subtypes, drug resistance, genetic barrier
ISSN: 1077-9450 (online)
1525-4135 (paper)
Publisher: Lippincott Williams & Wilkins
