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: Similarly, A371V and Q509L, which were selected in the background of D67N and K70R by high concentrations of AZT in vitro, show strong resistance to AZT and weak cross-resistance to 3TC, abacavir (ABC) and tenofovir (TNF/PMPA) in the presence of EEMs.
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, PMID: 19583845
2009
BMC infectious diseases
Table: K70R
Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria.
PMID: 19644383
2009
Journal of acquired immune deficiency syndromes (1999)
Abstract: The most common nucleoside reverse transcriptase inhibitor mutations observed were M184V (301, 89.1%) and K70R (91, 26.9%).
Result: The most common NRTI mutations observed were M184V (301, 89.1%), K70R (91, 26.9%), D67N (75, 22.2%), T215Y (61, 18.0%), T215F (51, 15.1%), M41L (46, 13.6%), K219Q (45, 13.3%), S68G (43, 12.7%), and K65R (37, 10.9%).
Thymidine analogue resistance suppression by V75I of HIV-1 reverse transcriptase: effects of substituting valine 75 on stavudine excision and discrimination.
PMID: 19801659
2009
The Journal of biological chemistry
Abstract: M41L/A62V/T69SSS/K70R/T215Y), the introduction of V75I led to a significant decrease of its ATP-dependent excision activity on AZT-, d4T-, and acyclovir-terminated primers.
Abstract: Recombinant HIV-1 containing the M41L/A62V/T69SSS/K70R/V75I/T215Y RT showed 18.3- and 1.5-fold increased susceptibility to AZT and d4T, respectively, in comparison with virus containing the M41L/A62V/T69SSS/K70R
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 M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N, which are primary resistance mutations for AZT and stavudine, are called thymidine analog mutations (TAMs), AZTr, or excision-enhancing mutations.
Figure:
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.
RT-SHIV subpopulation dynamics in infected macaques during anti-HIV therapy.
Discussion: The 214F mutation is associated with nucleoside analogue mutation cluster 2 (D67N+K70R+K219Q+T215F) and negatively associated with nucleotide analogue mutation cluster 1 (M41L+L210W+T215Y).
Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa.
Introduction: This second-generation NRTI showed improved antiviral activity against infections harboring TAMs (D67N, K70R and T215Y) and NAMs (Q151M).
Introduction: Two distinct TAM (TAM-1 and -2) pathways lead to the stepwise accumulation of major (M41L, K70R and T215Y/F), minor/secondary (D67N and L210W) and compensatory (E44D, V118I and H208Y) mutations that confer a 5-500-fold reduced susceptibility to AZT and broad cross-resistance between NRTIs (Figure 1).
AZT resistance of simian foamy virus reverse transcriptase is based on the excision of AZTMP in the presence of ATP.