TY - JOUR
T1 - Effect of human immunodeficiency virus type 1 protease inhibitor therapy and subtype on development of resistance in subtypes B and G
AU - Palma, Ana Carolina
AU - Abecasis, Ana Barroso
AU - Vercauteren, Jurgen
AU - Carvalho, Ana P.
AU - Cabanas, Joaquim
AU - Vandamme, Anne-Mieke
AU - Camacho, Ricardo Jorge
N1 - 2009 Elsevier B.V. All rights reserved.
PY - 2010/4
Y1 - 2010/4
N2 - 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.
AB - 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.
KW - Amino Acid Substitution
KW - Drug Resistance, Viral
KW - Genetic Variation
KW - HIV Infections
KW - HIV Protease
KW - HIV Protease Inhibitors
KW - HIV-1
KW - Humans
KW - Indinavir
KW - Lopinavir
KW - Phylogeny
KW - Pyrimidinones
KW - Selection, Genetic
KW - Sequence Analysis, Protein
KW - Comparative Study
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-77951094151&origin=inward&txGid=6f6717f5bbce778c97266cfdc187903d#
UR - https://www.sciencedirect.com/science/article/abs/pii/S156713480900152X?via%3Dihub
U2 - 10.1016/j.meegid.2009.06.019
DO - 10.1016/j.meegid.2009.06.019
M3 - Article
C2 - 19577015
VL - 10
SP - 373
EP - 379
JO - Infection, Genetics and Evolution
JF - Infection, Genetics and Evolution
SN - 1567-1348
IS - 3
ER -