The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations.
Abstract: Among >60,000 clinical samples submitted for genotype analysis that contained one or more NRTI resistance mutations, the frequency of K65R increased from 0.4% in 1998 to 3.6% in 2003.
Abstract: Among samples with K65R, a strong negative association was evident with the TAMs M41L, D67N, L210W, T215Y/F, and K219Q/E (P<0.005) but not with other NRTI mutations, including the Q151M complex.
Abstract: In addition, TAMs antagonized the phenotypic effect of K65R, reducing resistance to tenofovir, abacavir, 2',3'-dideoxycytidine, dideoxyinosine, and stavudine.
Abstract: In conc
In vitro evaluation of the anti-HIV activity and metabolic interactions of tenofovir and emtricitabine.
Abstract: The anti-HIV activity of the combination was studied in the human T leukaemic MT-2 cell line against wild-type or mutant virus (K65R and M184V) and in PBMCs against wild-type virus.
Virological response to a triple nucleoside/nucleotide analogue regimen over 48 weeks in HIV-1-infected adults in Africa.
Abstract: Fourteen had M184V [10 with one to four additional nucleoside analogue mutations (NAMs)]; one had three NAMs only; and the remaining three had K65R.
Abstract: In this population, who were infected with HIV-1 subtypes A, C or D, M184V with or without NAMs was the most common route to resistance, whereas K65R was identified less often.
HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture.
Abstract: K65R appeared after 55 and 73 weeks in two CRF1_AE selections with tenofovir.
Abstract: CONCLUSION: Tenofovir -based regimens will need to be carefully monitored in subtype C infections for the possible selection of K65R.
Abstract: Phenotypic assays determined the effects of the K65R substitution in reverse transcriptase (RT) on drug susceptibility.
Abstract: The K65R mutation (AAG-->AGG) arose with tenofovir by week 12 in four subtype C selections.
Abstract: The K65R transitions in subtype C and other subtypes (AGG and AGA) conferred similar 6.5-10-fold resistance to tenofovir and five to 25-fold cross-resistance to each of abacavir, lamivudine, and didanosine, while not affecting zidovudine susceptibility.
Alkoxyalkyl esters of (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine are potent inhibitors of the replication of wild-type and drug-resistant human immunodeficiency virus type 1 in vitro.
PMID: 16870786
2006
Antimicrobial agents and chemotherapy
Abstract: Resistance to HDP-(S)-HPMPA and ODE-(S)-HPMPA was noted for a mutant with mutation K65R.
Antagonism between the HIV-1 reverse-transcriptase mutation K65R and thymidine-analogue mutations at the genomic level.
PMID: 16897664
2006
The Journal of infectious diseases
Abstract: K65R and multiple TAMs were rarely detected (<0.1%) in the same plasma sample.
Abstract: K65R was never found on the same genome with T215F/Y and >or=2 other TAMs, except in the presence of the Q151M multiple nucleoside reverse-transcriptase inhibitor (NRTI)--resistance complex.
Abstract: Prior virologic and biochemical studies have shown phenotypic antagonism between K65R and multiple thymidine-analogue mutations (TAMs) in site-directed mutants tested in vitro.
Abstract: Samples with both K65R and >or=3 TAMs (n=21) were further analyzed by use of single-genome sequencing.
Abstract: These results indicate that antagonism between the K65R
Resistance development over 144 weeks in treatment-naive patients receiving tenofovir disoproxil fumarate or stavudine with lamivudine and efavirenz in Study 903.
Abstract: Analysis of 73 clones (patient 1: 12 clones; patient 2: 27 clones; patient 3: 13 clones; patient 4: 21 clones) showed that 29 clones harboured K65R and L74V/I mutations.
Abstract: OBJECTIVE: To determine to which extent the mutations K65R, L74V/I and T215Y/F are linked to the same HIV-1 genome.
Abstract: Twenty-three per cent of clones from the two bulk sequences harbouring K65K/R and T215T/Y genotypic mixtures contained K65R and T215Y on the same viral genome.
HIV-1 reverse transcriptase (RT) genotypic patterns and treatment characteristics associated with the K65R RT mutation.
Abstract: K65R was associated with nucleoside RT inhibitor-based regimens in 22 patients, and with tenofovir disoproxil fumarate, lamivudine, didanosine and abaca
Abstract: BACKGROUND: The K65R HIV-1 reverse transcriptase (RT) mutation is a multidrug resistance mutation which may be correlated with specific antiretroviral combinations and with the presence or absence of other RT resistance mutations.
Abstract: CONCLUSION: The K65R mutation may emerge preferentially in the absence of zidovudine and TAMs, suggesting the possibility of an antagonistic interaction between K65 and TAMs.
Abstract: Genotypic patterns and treatment characteristics were examined at the time of detection of the K65R mutation.
In vitro human immunodeficiency virus type 1 resistance selections with combinations of tenofovir and emtricitabine or abacavir and lamivudine.
PMID: 16982781
2006
Antimicrobial agents and chemotherapy
Abstract: Abacavir resistance was characterized by the accumulation of the M184V, Y115F, and K65R mutations in the abacavir culture, while the M184V and L74V mutations were selected in combination with lamivudine.
Abstract: At intermediate concentrations of emtricitabine and tenofovir, viruses harboring the K65R mutation or a novel K65N and K70R double mutation grew before they gave rise to mutants with K65R and M184V/I double mutations at higher emtricitabine concentrations.
Abstract: At low concentrations of emtricitabine and tenofovir, the M184I mutation appeared first, followed by the
HIV mutation literature information.
PMID: 
2006
Journal of virology
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