literature

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.

PMID: 19428602 2009 Antiviral research

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.

PMID: 19889213 2009 Retrovirology

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.

PMID: 19911963 2009 Clinical infectious diseases

Method: Thymidine associated mutations (TAMs) were M41L, D67N, K70R, L210W, T215Y/F, K219Q/E and multi-NRTI mutations included TAMS, K65R, and L74V.

Table: K70R

HIV type 1 subtype diversity and drug resistance among HIV type 1-infected Kenyan patients initiating antiretroviral therapy.

PMID: 19954302 2009 AIDS research and human retroviruses

Abstract: Of these patients, three had nucleoside RTI resistance mutations, such as M184V, K65R, D67N, K70R, and K219Q.

The K65R mutation in HIV-1 reverse transcriptase: genetic barriers, resistance profile and clinical implications.

PMID: 20190870 2009 HIV therapy

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.

PMID: 18096624 2008 Nucleic acids research

Discussion: The mutations involved in the enhanced excision of AZTMP in HIV-1 RT are M41L, D67N, K70R, T215Y/F and K219Q/E (Figure 7).