Περίληψη:
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.
Συγγραφείς:
van de Vijver, DA
Wensing, AMJ
Angarano, G
Asjo, B and
Balotta, C
Boeri, E
Camacho, R
Chaix, ML
Costagliola, D
and De Luca, A
Derdelinckx, I
Grossman, Z
Hamouda, O and
Hatzakis, A
Hemmer, R
Hoepelman, A
Horban, A
Korn, K and
Kucherer, C
Leitner, T
Loveday, C
MacRae, E
Maljkovic, I
and de Mendoza, C
Meyer, L
Nielsen, C
de Coul, ELMO and
Ormaasen, V
Paraskevis, D
Perrin, L
Puchhammer-Stockl, E and
Ruiz, L
Salminen, M
Schmit, JC
Schneider, F
Schuurman, R
and Soriano, V
Stanczak, G
Stanojevic, M
Vandamme, AM and
Van Laethem, K
Violin, M
Wilbe, K
Yerly, S
Zazzi, M and
Boucher, CAB
SPREAD Programme
