Title
Effect of human immunodeficiency virus type 1 protease inhibitor therapy and subtype on development of resistance in subtypes B and GEffect of human immunodeficiency virus type 1 protease inhibitor therapy and subtype on development of resistance in subtypes B and G
Author
Faculty/Department
Faculty of Applied Economics
Research group
Faculty of Applied Economics - other
Accountancy and Finance
Publication type
article
Publication
Amsterdam,
Subject
Human medicine
Source (journal)
Infection, genetics and evolution. - Amsterdam
Volume/pages
10(2010):3, p. 373-379
ISSN
1567-1348
vabb
c:vabb:374428
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
Europe is currently observing a significant rise in non-B subtypes. Consequently, the effect of genetic variability on therapy response or genotypic resistance interpretation algorithms is an emerging concern. The purpose of this study is to investigate the amino acid substitutions selected under drug pressure in the protease of human immunodeficiency virus type 1 (HIV-1) subtypes B and G, and determine if there are any significant differences. We investigated therapy-related and subtype-related substitutions in the protease, considering subtype, overall protease inhibitor treatment and individual drug exposure. Many mutations were significantly related to protease inhibitor (PI) therapy, with mutations exclusive to subtype B or subtype G. Some mutations are at positions related to resistance in both subtypes, but the amino acid substitution is different. Other mutations were significantly associated with subtype and PI selective pressure (p < 0.05), pointing towards a differential selective pressure in both subtypes. We confirmed previous reports on the subtype-dependent selection of D30N and 89I, and identified a new mutation with such differential selective pressure: 37D was preferentially selected by lopinavir in subtype B. Other novel mutations found under therapy pressure were 13A, 35N, K55R, I66F, I72L/T, T74S, 82M and 89I/V. Our study indicates that even though in general, drug selective pressure and resistance pathways are relatively similar between subtypes B and G, some differences do occur, leading to subtype-dependent substitutions.
E-info
https://repository.uantwerpen.be/docman/iruaauth/c9cb73/499a5db08b5.pdf
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