Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity.
PMID: 22828721
2012
Journal of acquired immune deficiency syndromes (1999)
Method: Thymidine analogue mutations (TAMs) were defined as M41L, D67N, K70R, L210W, T215F/Y, K219E/Q.
Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy.
Introduction: However, combinations of M41L, D67N, K70R, L210W, T215F/Y and K219E/Q increase ATP-mediated excision of chain-terminating NRTIs (reviewed in ref.).
Introduction: Sequence analysis of HIV-1 isolates from patients receiving long-term therapy with AZT and/or d4T revealed that thymidine analogue resistance mutations (TAMs) acting through the excision mechanism associated in two different clusters: TAM1 (M41L, L210W and T215Y) and TAM2 (D67N, K70R, K219E/Q, and sometimes T215F).
HIV-1 drug resistance genotyping from antiretroviral therapy (ART) naive and first-line treatment failures in Djiboutian patients.
Result: The NRTI-associated mutations were D67N (2 strains), T69N (1), M184V (6), L210W (2), T215Y (2).
Table: D67N
Discussion: Accumulation of the other mutations observed included thymidine associated mutations (including M41L, D67N, K70R, L210W, T215Y/F, K219Q) results in increasing resistance to AZT, Tenofovir, D4T, Abacavir, and DDI .
Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C.
Discussion: Although some researchers characterize D67N as a TAM-2 pathway mutation, this change has also been found in a TAM-1 background, in agreement with our data.
Discussion: Furthermore, an additional mutation, D67N, was incorporated when the VL rebounded to original levels comparable to those before the onset of drug selection (figure 1B).
Discussion: However, RTC and RTC' data suggest that D67N and K70R were selected instead of T215F and then directed to TAM-2.
Discussion: However, three different final profiles with D67N and K70R mutations were observed in all replicates: T215I or T215F or T215F/I.
Screening for and verification of novel mutations associated with drug resistance in the HIV type 1 subtype B(') in China.
Result: The 9 mutations M41L, D67N, K70R, K103N, Y181C, M184V, T215Y, L283I and N348I resulted in resistance to NRTIs or NNRTIs, but the impact of 7 mutations at 6 positions (D123E, V292I, K366R, T369A, T369V, A371V and I375V) on antiviral drug response was unknown.
Virological failure rates and HIV-1 drug resistance patterns in patients on first-line antiretroviral treatment in semirural and rural Gabon.
PMID: 23199801
2012
Journal of the International AIDS Society
Result: TAM-2 mutations included K219Q/E/R (n=4), D67N/G (n=4), and K70R (n=3).
Figure: M41L, L210W, and T215Y mutations are indicative of the TAM-1 pathway; D67N/G, K70R, T215F, and K219Q/E/R mutations are indicative of the TAM-2 pathway.
Monitoring HIV viral load in resource limited settings: still a matter of debate?
Result: One patient carried Q151M mutation, associated with M41L, D67N, T215F and M184V, conferring pan-nucleoside resistance, except to tenofovir.
Result: The most frequent TAMs were T215F/Y (11/12, 91.7%), M41L (10/12, 83.3%), L210W (3/12, 27,3%), D67N (3/12, 25.0%),
Effect of translocation defective reverse transcriptase inhibitors on the activity of N348I, a connection subdomain drug resistant HIV-1 reverse transcriptase mutant.
PMID: 23273211
2012
Cellular and molecular biology (Noisy-le-Grand, France)
Discussion: The D67N/K70R/L210Q/T215F set of mutations are the classical thymidine-associated mutations (TAMs), which are known to cause resistance to AZT by enhancing excision of AZT-terminated primers.
Discussion: Unlike D67N/K70R/L210Q/T215F RT, the Q151M complex decreases susceptibility to NRTIs by decreasing incorporation efficiency of the inhibitors rather than increasing excision and unblocking of chain-terminated primers.
Discussion: We report that both EFdA-TP and ENdA-TP are very potent inhibitors of N348I, D67N/
Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis.
PMID: 23305651
2012
Journal of the International AIDS Society
Method: Tenofovir-associated resistance mutations included K65R, T69 insertion, K70E and >=3 thymidine-analogue mutations (TAMs; M41L, D67N, K70R, L210W, T215F/Y, K219Q/E), inclusive of either M41L or L210W.
"K70Q adds high-level tenofovir resistance to ""Q151M complex"" HIV reverse transcriptase through the enhanced discrimination mechanism."
Introduction: Increased excision of NRTIs is imparted by Excision Enhancement Mutations, typically M41L, D67N, K70R, T215Y/F, L210W, and K219E/Q (also known as Thymidine Associated Mutations, or TAMs).
Discussion: Mutations at position 70 of RT have been known to confer NRTI resistance by two distinct mechanisms: K70R combined with at least two excision enhancing mutations, D67N and T215Y, enhances ATP-mediated excision of AZT and d4T (excision-dependent mechanism).
HIV mutation literature information.
PMID: 
2012
Journal of acquired immune deficiency syndromes (1999)
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