Polymorphic mutations associated with the emergence of the multinucleoside/tide resistance mutations 69 insertion and Q151M.
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.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, University of Zürich, Zürich, Switzerland. alexandra.scherrer@usz.ch
Alexandra U
AU
Scherrer
Viktor
V
von Wyl
Matthias
M
Götte
Thomas
T
Klimkait
Cristina
C
Cellerai
Sabine
S
Yerly
Jürg
J
Böni
Leonhard
L
Held
Bruno
B
Ledergerber
Huldrych F
HF
Günthard
D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000494:pharmacology; D015331:Cohort Studies; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005787:Gene Frequency; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D016254:Mutagenesis, Insertional; D009154:Mutation; D009705:Nucleosides / Q000235:genetics; D013557:Switzerland; D013936:Thymidine / Q000031:analogs & derivatives* / Q000235:genetics
D019380:Anti-HIV Agents; D009705:Nucleosides; D054303:HIV Reverse Transcriptase; D013936:Thymidine