literature

The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance.

PMID: 25341667 2014 Viruses

Introduction: Data from this study shows that while K65R was present in 82% of genomes without TAMs, and at low frequency in the presence of <3 TAMs; no sequences were identified with K65R, T215F/Y and >= 2 TAMs in the absence of the Q151M multi-drug resistant complex.

Introduction: Several mutations (the thymidine analog mutations, TAM) are required for high-level AZT resistance by excision, and include M41L, D67N, K70R, T215F or Y and K219E or Q.

Introduction: The association of Q151M and other Q151M complex mutations with K65R,

PMID: 24969820 2014 The Biochemical journal

Abstract: HIV-1 resistance to zidovudine [AZT (azidothymidine)] is associated with selection of the mutations M41L, D67N, K70R, L210W, T215F/Y and K219Q/E in RT (reverse transcriptase).

Introduction:

Result: Consistent with previously published data, we found that RTs containing M41L/L210W/T215Y or D67N/K70R/T215F/K219Q increased the enzyme's apparent affinity for ATP (KM) and the rate of excision (kexcision) (Table 1).

Development and customization of a color-coded microbeads-based assay for drug resistance in HIV-1 reverse transcriptase.

PMID: 25314293 2014 PloS one

Result: DR mutations were found at codons M41L (n = 22), K65R (n = 3), K70R (n = 10), K103N (n = 7), M184V (n = 21) and T215Y/F (n = 22) in 40 specimens (Table 2).

Table: T215F

Figure: wild type; 2, M41L-TTG; 3, M41L-CTG; 4,

HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia.

PMID: 25141905 2014 Journal of the International AIDS Society

Introduction: There are two TAM pathways: type I (M41L, L210W and T215Y) and type II (D67N, K70R, T215F and K219Q/E); the former conferring higher levels of resistance and cross-resistance.

Result: A total of 35 patients had at least 1 TAM, with the following distribution: M41L (16%), D67N (15%), K70R (9%), L210W (11%), T215Y (16%), T215F (11%), K219Q (5%) and K219E (2%).

2014 Update of the drug resistance mutations in HIV-1.

PMID: 25101529 2014 Topics in antiviral medicine

Discussion: Mutations known to be selected by TAMs (ie, M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E) also confer reduced susceptibility to all currently approved nRTIs.

Discussion: The presence of 3 of the following mutations:M41L, D67N, L210W, T215Y/F, K219Q/E:is associated with resistance to didanosine.

Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia.

PMID: 25166019 2014 PloS one

Result: The TAM2 pathway (D67N, K70R, T215F, and K219Q/E) was present in 5/22, 4/22, 8/22, 2/22 patients.

Transmitted HIV drug resistance in treatment-naive Romanian patients.

PMID: 23592112 2013 Journal of medical virology

Result: Thymidine analogues mutations (TAMs), selected mostly by ZDV and d4T, were prevalent (6/9; 66.66%), with type II TAMs being more frequently detected (4/9; 44.44%): K70R and K219Q (each in three cases), D67N and T215F (each in two cases).

Evaluation of WHO immunologic criteria for treatment failure: implications for detection of virologic failure, evolution of drug resistance and choice of second-line therapy in India.

PMID: 23735817 2013 Journal of the International AIDS Society

Method: Nucleoside reverse transcriptase inhibitor (NRTI) mutations included in this analysis were as follows: M184V, M184I and M184V/I for lamivudine (3TC) and emtricitabine (FTC) resistance; K65R and K70E, associated with tenofovir (TDF) resistance; thymidine analogue mutations (TAMs) M41L, D67N, K70R, L210W, T215Y, T215F, K219Q, and K219 E, associated with resistance to multiple NRTIs; and multinucleoside mutations, including the

Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA.

PMID: 23800377 2013 Retrovirology

Introduction: The excision reaction is facilitated by Excision Enhancement Mutations (EEMs), typically M41L, D67N, K70R, T215Y/F, L210W, and K219E/Q, which are also known as Thymidine Associated Mutations (TAMs) because they were historically linked to resistance to thymidine analogs AZT and d4T.

From the chemistry of epoxy-sugar nucleosides to the discovery of anti-HIV agent 4'-ethynylstavudine-Festinavir.

PMID: 23092278 2013 Current pharmaceutical design

Introduction: A012D contains four NRTI-associated mutations (NAMs) (D67K, K70R, T215F and K219Q), which confer a high level (210-fold) resistance to zidovudine.