Uncommon mutations at residue positions critical for enfuvirtide (T-20) resistance in enfuvirtide-naive patients infected with subtype B and non-B HIV-1 strains

被引:45
作者
Roman, F
Gonzalez, D
Lambert, C
Deroo, S
Fischer, A
Baurith, T
Staub, T
Boulmé, R
Arendt, V
Schneider, F
Hemmer, R
Schmit, JC
机构
[1] Ctr Rech Publ Sante, Retrovirol Lab, Luxembourg, Luxembourg
[2] Adv Biol Labs, Biomed Informat Unit, Luxembourg, Luxembourg
关键词
enfuvirtide; primary resistance; subtypes;
D O I
10.1097/00126334-200306010-00003
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Enfuvirtide (T-20) is the lead compound of the new class of antiretroviral drugs called fusion inhibitors. T-20 resistance-associated mutations located in the heptad repeat 1 (HR-1) domain of gp41 have been described in vitro and in clinical trials. In this study, the authors investigated the primary genotypic T-20 resistance in subtype B and non-B HIV-1 strains from patients at the beginning of their follow-up in the Luxembourg HIV Cohort as well as the emergence of primary resistance to T-20 in patients who had long-term infection with subtype B HIV-1 strains. HR-1 fragments including the gp41 amino acid 36-45, T-20-sensitive region were screened for amino acid variation. No classic T-20 resistance-associated mutations were identified in subtype B or non-B isolates. However, several uncommon mutations were found at residues 37, 39, and 42 for subtype B isolates and at residue 42 for a subtype non-B isolate. The results indicate that primary genotypic T-20 resistance seems to be rare in HIV-1, regardless of subtype or prior antiretroviral therapy (excluding fusion inhibitors). However, episodic variation within HR-1 can occur and needs further phenotypic evaluation in accurate fusion inhibitor resistance assays.
引用
收藏
页码:134 / 139
页数:6
相关论文
共 21 条
[1]   HIV entry and its inhibition [J].
Chan, DC ;
Kim, PS .
CELL, 1998, 93 (05) :681-684
[2]   Current evidence and future directions for targeting HIV entry - Therapeutic and prophylactic strategies [J].
D'Souza, MP ;
Cairns, JS ;
Plaeger, SF .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2000, 284 (02) :215-222
[3]   Sensitivity of human immunodeficiency virus type 1 to the fusion inhibitor T-20 is modulated by coreceptor specificity defined by the V3 loop of gp120 [J].
Derdeyn, CA ;
Decker, JM ;
Sfakianos, JN ;
Wu, XY ;
O'Brien, WA ;
Ratner, L ;
Kappes, JC ;
Shaw, GM ;
Hunter, E .
JOURNAL OF VIROLOGY, 2000, 74 (18) :8358-8367
[4]   HIV-1 subtypes in Luxembourg, 1983-2000 [J].
Deroo, S ;
Robert, I ;
Fontaine, E ;
Lambert, C ;
Plesséria, JM ;
Arendt, V ;
Staub, T ;
Hemmer, R ;
Schneider, F ;
Schmit, JC .
AIDS, 2002, 16 (18) :2461-2467
[5]  
Felsenstein J., 1993, PHYLIP PHYLOGENY INF
[6]  
Greenberg ML, 2002, ANTIVIR THER, V7, pS14
[7]   Resistance mutation in HIV entry inhibitors [J].
Hanna, SL ;
Yang, CF ;
Owen, SM ;
Lal, RB .
AIDS, 2002, 16 (12) :1603-1608
[8]   Membrane-anchored peptide inhibits human immunodeficiency virus entry [J].
Hildinger, M ;
Dittmar, MT ;
Schult-Dietrich, P ;
Fehse, B ;
Schnierle, BS ;
Thaler, S ;
Stiegler, G ;
Welker, R ;
von Laer, D .
JOURNAL OF VIROLOGY, 2001, 75 (06) :3038-3042
[9]   Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry [J].
Kilby, JM ;
Hopkins, S ;
Venetta, TM ;
DiMassimo, B ;
Cloud, GA ;
Lee, JY ;
Alldredge, L ;
Hunter, E ;
Lambert, D ;
Bolognesi, D ;
Mathews, T ;
Johnson, MR ;
Nowak, MA ;
Shaw, GM ;
Saag, MS .
NATURE MEDICINE, 1998, 4 (11) :1302-1307
[10]  
KUIKEN C, 1908, HIV SEQUENCE COMPEND