Abstract: K65R and TAMs rarely occur together in patients.
Abstract: K65R mediated decreased binding/incorporation of TFV and AZT (increased Ki/Km of 7.1- and 4.3-fold, respectively), but also decreased excision of TFV and AZT (0.7- and 0.3-fold, respectively) when compared with wild-type RT.
Abstract: HIV-1 with TAMs shows reduced susceptibility to all NRTIs, most notably AZT, whereas HIV-1 with K65R shows reduced susceptibility to all NRTIs except AZT.
Abstract: However, when present together, K65R can restore susceptibility to AZT.
Abstract: Molecular modelling studies suggest that K65R creates additional hydrogen bonds that reduce the conformational mobility of PMID: 16640104
2006
Antiviral therapy
Abstract: In 17 genotypic tests available at failure, no K65R mutation was detected, whereas a trend for an increasing prevalence of d4T-associated mutations was found.
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 mutation literature information.
PMID: 
2006
Antiviral therapy
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