literature

HIV mutation literature information.

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).

Identification of a novel resistance (E40F) and compensatory (K43E) substitution in HIV-1 reverse transcriptase.

PMID: 18271957 2008 Retrovirology

Result: Mutations from the TAM-2 pathway (D67N, K70R, T215F and K219Q/E) were only weakly or even negatively associated with the E40F and K43E changes, with the exception of the D67N

Discussion: In this study we show that these E40F and K43E changes are highly associated with mutations from the TAM-1 pathway (M41L, L210W and T215Y) and less with the amino acid changes from the TAM-2 pathway (D67N, K70R, T215F and K219Q/E) (Table 2).

Prevalence of genotypic resistance to nucleoside analogues, nonnucleoside analogues, and protease inhibitors in HIV-infected persons in Athens, Greece.

PMID: 18275347 2008 AIDS research and human retroviruses

Abstract: The most frequent ARMs of each drug category were to NRTIs at codons M184V [present in 149 tests (63.6%)], M41L [79 (33.8%)], K70R [66 (28.2%)], M184VI [58 (24.8%)], T215YF [53 (22.7%)], D67N [82 (35.0%)], T215Y [72 (30.8%)], K219Q [47 (20.1%)], K219E/Q [54 (23.1%)], and L210W [49 (20.9%)], respectively.

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