Abstract: We determined five crystal structures: wild-type reverse transcriptase-double-stranded DNA (RT-dsDNA)-AZTppppA; AZT-resistant (AZTr; M41L D67N K70R T215Y K219Q) RT-dsDNA-AZTppppA; AZTr RT-dsDNA terminated with AZT at
Introduction: The mutations commonly associated with excision-mediated AZT resistance are M41L, D67N, K70R, L210W, T215Y, T215F, K219Q and K219E.
Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa.
Result: HIV-1-associated thymidine analogue mutations (M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E) were not found, with the exception of K70R, which was present in a strain from 1 patient (in conjunction with K65R, Q151M, and 219E, the latter of which is commonly present in wild-type HIV-2 in ARV therapy naive patients).
The public health approach to identify antiretroviral therapy failure: high-level nucleoside reverse transcriptase inhibitor resistance among Malawians failing first-line antiretroviral therapy.
Method: NRTI mutations included K65R and K70E (associated with TDF resistance), thymidine analog mutations (TAMs) M41L, D67N, K70R, L210W, T215Y, T215F, K219Q, and K219E, and multinucleoside mutations, including the 69 insertion complex and the 151 complex.
Result: The most frequent TAMs were T215 F/Y (73%), D67N (53%), K70R (36%), M41L (36%), K219 Q/E (23%), and L210W (23%).
Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients.
Introduction: The excision mechanism is associated with mutations at the polymerase domain, including M41L, D67N, K70R, L210W, T215F/Y and K219E/Q (excision-containing mutations, EEMs, also known as thymidine analogue-associated mutations [TAMs]).
Discussion: The Type I EEMs (M41L, L210W, T215Y and occasionally the D67N mutation) appear twice as frequently as Type II EEMs (D67N, K70R, T215F and K219Q mutation) in subtype B, whereas Type II EEMs are mostly obse
Virological efficacy and emergence of drug resistance in adults on antiretroviral treatment in rural Tanzania.
Result: The most common TAM was M41L, occurring in 5 cases; D67N and K219Q were each present in 3 samples.
Minority variants associated with transmitted and acquired HIV-1 nonnucleoside reverse transcriptase inhibitor resistance: implications for the use of second-generation nonnucleoside reverse transcriptase inhibitors.
PMID: 19734799
2009
Journal of acquired immune deficiency syndromes (1999)
Discussion: For example, PID 8048 had the NRTI-resistance mutation K65R and the accessory NNRTI-resistance mutation P225H and PID 30062 contained the NRTI-resistance mutations M184V, L210W, T215Y, and K219Q.
Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance.
PMID: 19812032
2009
The Journal of biological chemistry
Introduction: Mutations
Figure: Superposition of excision-enhancing mutation or TAM (M41L, D67N, K70R, T215Y, and K219Q) RT dsDNA AZTppppA structure4 on K65R RT dsDNA dATP structure at their dNTP-binding sites; AZTppppA is the product of AZT monophosphate by ATP-mediated excision.
Discussion: TAMs (M41L, D67N, K70R, T215Y/F, and K219Q/E/N) cause enhanced NRTI excision, a major mechanism of resistance where the excision of incorporated nucleotides is mediated by ATP.
HIV mutation literature information.
PMID: 
2010
Nature structural & molecular biology
Browser Board
Co-occurred Entities
Filtrator
ViMRT