Polymorphic mutations associated with the emergence of the multinucleoside/tide resistance mutations 69 insertion and Q151M.
Détails
ID Serval
serval:BIB_9C1A5E8F92FD
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Polymorphic mutations associated with the emergence of the multinucleoside/tide resistance mutations 69 insertion and Q151M.
Périodique
Journal of Acquired Immune Deficiency Syndromes
Collaborateur⸱rice⸱s
Swiss HIV Cohort Study
Contributeur⸱rice⸱s
Battegay M., Bernasconi E., Böni J., Bucher HC., Bürgisser P., Calmy A., Cattacin S., Cavassini M., Dubs R., Egger M., Elzi L., Fischer M., Flepp M., Fontana A., Francioli P., Furrer H., Fux CA., Gorgievski M., Günthard H., Hirsch HH., Hirschel B., Hösli I., Kahlert C., Kaiser L., Karrer U., Kind C., Klimkait T., Ledergerber B., Martinetti G., Müller N., Nadal D., Paccaud F., Pantaleo G., Rauch A., Regenass S., Rickenbach M., Rudin C., Schmid P., Schultze D., Schüpbach J., Speck R., de Tejada BM. , Taffé P., Telenti A., Trkola A., Vernazza P., Weber R., Yerly S.
ISSN
1944-7884 (Electronic)
ISSN-L
1525-4135
Statut éditorial
Publié
Date de publication
2012
Volume
59
Numéro
2
Pages
105-112
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
BACKGROUND: We hypothesized that polymorphic mutations exist that are associated with the emergence of the multinucleoside resistance mutations (MNR), 69 insertion and Q151M.
METHODS: The Swiss HIV Cohort Study was screened, and the frequencies of polymorphic mutations in HIV-1 (subtype B) were compared between patients detected with the 69 insertion (n = 17), Q151M (n = 29), ≥2 thymidine analogue mutations (TAM) 1 (n = 400) or ≥2 TAM 2 (n = 249). Logistic regressions adjusted for the antiretroviral treatment history were performed to analyze the association of the polymorphic mutations with MNR.
RESULTS: The 69 insertion and TAM 1 were strongly associated and occurred in 94.1% (16 of 17) together. The 69 insertion seemed to emerge as a consequence of the TAM 1 pathway (median years until detection: 6.8 compared with 4.4 for ≥2 TAM 1, P Wilcoxon = 0.009). Frequencies of 8 polymorphic mutations (K43E, V60I, S68G, S162C, T165I, I202V, R211K, F214L) were significantly different between groups. Logistic regression showed that F214L and V60I were associated with the emergence of Q151M/TAM 2 opposed to 69 insertion/TAM 1. S68G, T165I, and I202V were associated with Q151M instead of TAM 2.
CONCLUSIONS: Besides antiretroviral therapy, polymorphic mutations may contribute to the emergence of specific MNR mutations.
METHODS: The Swiss HIV Cohort Study was screened, and the frequencies of polymorphic mutations in HIV-1 (subtype B) were compared between patients detected with the 69 insertion (n = 17), Q151M (n = 29), ≥2 thymidine analogue mutations (TAM) 1 (n = 400) or ≥2 TAM 2 (n = 249). Logistic regressions adjusted for the antiretroviral treatment history were performed to analyze the association of the polymorphic mutations with MNR.
RESULTS: The 69 insertion and TAM 1 were strongly associated and occurred in 94.1% (16 of 17) together. The 69 insertion seemed to emerge as a consequence of the TAM 1 pathway (median years until detection: 6.8 compared with 4.4 for ≥2 TAM 1, P Wilcoxon = 0.009). Frequencies of 8 polymorphic mutations (K43E, V60I, S68G, S162C, T165I, I202V, R211K, F214L) were significantly different between groups. Logistic regression showed that F214L and V60I were associated with the emergence of Q151M/TAM 2 opposed to 69 insertion/TAM 1. S68G, T165I, and I202V were associated with Q151M instead of TAM 2.
CONCLUSIONS: Besides antiretroviral therapy, polymorphic mutations may contribute to the emergence of specific MNR mutations.
Mots-clé
Amino Acid Substitution/genetics, Anti-HIV Agents/pharmacology, Cohort Studies, Drug Resistance, Multiple, Viral/genetics, Gene Frequency, HIV Infections/drug therapy, HIV Infections/genetics, HIV Reverse Transcriptase/genetics, HIV-1/drug effects, HIV-1/genetics, Humans, Logistic Models, Mutagenesis, Insertional, Mutation, Nucleosides/genetics, Switzerland, Thymidine/analogs & derivatives, Thymidine/genetics
Pubmed
Web of science
Création de la notice
06/03/2012 20:27
Dernière modification de la notice
20/08/2019 16:02
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