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Polymorphic mutations associated with the emergence of the multi-nucleoside/tide resistance mutations 69 insertion and Q151M


Scherrer, A U; von Wyl, V; Götte, M; Klimkait, T; Cellerai, C; Yerly, S; Böni, J; Held, L; Ledergerber, B; Günthard, H F (2012). Polymorphic mutations associated with the emergence of the multi-nucleoside/tide resistance mutations 69 insertion and Q151M. Journal of Acquired Immune Deficiency Syndromes, 59(2):105-112.

Abstract

BACKGROUND: We hypothesized that polymorphic mutations exist that are associated with the emergence of the multi-nucleoside resistance mutations (MNR), 69 insertion and Q151M. METHODS: The Swiss HIV Cohort Study (SHCS) 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 1were strongly associated and occurred in 94.1% (16/17) together. The 69 insertion seemed to emerge as a consequence of the TAM 1 pathway (median years until detection: 6.8 compared to 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.

BACKGROUND: We hypothesized that polymorphic mutations exist that are associated with the emergence of the multi-nucleoside resistance mutations (MNR), 69 insertion and Q151M. METHODS: The Swiss HIV Cohort Study (SHCS) 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 1were strongly associated and occurred in 94.1% (16/17) together. The 69 insertion seemed to emerge as a consequence of the TAM 1 pathway (median years until detection: 6.8 compared to 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.

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4 citations in Web of Science®
4 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Virology
04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2012
Deposited On:20 Mar 2012 08:42
Last Modified:05 Apr 2016 15:22
Publisher:Lippincott Wiliams & Wilkins
ISSN:1525-4135
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1097/QAI.0b013e31823c8b69
PubMed ID:22027876

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