Discussion: Single mutations in reverse transcriptase (RT) confer resistance to nucleoside RT inhibitors (M184V, K65R) and nonnucleoside RT inhibitors (Y181C) without significantly compromising viral fitness, yet these drugs are used in most antiretroviral regimens.
A comparison of the phenotypic susceptibility profiles of emtricitabine and lamivudine.
Result: In comparison, mutations such as K65R, K70E, L74V, Q151M, and M184V increase the selectivity of RT for incorporation of natural deoxynucleoside triphosphate substrate versus the NRTI-triphosphate.
Virological response to salvage therapy in HIV-infected persons carrying the reverse transcriptase K65R mutation.
Abstract: BACKGROUND: The effect of the HIV reverse transcriptase K65R mutation on virological response to salvage therapy has not been clearly defined.
Abstract: CONCLUSIONS: Development of the K65R mutation does not preclude a high rate of virological response to rescue therapy.
Abstract: METHODS: From six Italian clinical centres, all consecutive patients starting salvage antiretroviral therapy after virological failure in the presence of the K65R mutation identified by a genotypic resistance test were selected.
The balance between NRTI discrimination and excision drives the susceptibility of HIV-1 RT mutants K65R, M184V and K65r+M184V.
Abstract: For TFV, decreased excision by K65R and K65R+M184V may partially counteract the K65R-driven decrease in incorporation relative to wild-type resulting in only low levels of TFV resistance.
Abstract: For most NRTIs, the primary mechanism of resistance by K65R, M184V and K65R+M184V mutant RTs is to disrupt the NRTI-binding/incorporation steps.
Abstract: In cell culture, the K65R+M184V virus showed slightly increased susceptibility to TFV, AZT and d4T compared with K65R alone, but showed f
Viral fitness: relation to drug resistance mutations and mechanisms involved: nucleoside reverse transcriptase inhibitor mutations.
PMID: 19372871
2007
Current opinion in HIV and AIDS
Abstract: Further studies have helped explain the antagonistic effects between amino acid substitutions, K65R, L74V, M184V, and thymidine analogue mutations, showing how viral replicative fitness influences the evolution of thymidine analogue resistance pathways.
Mechanisms of resistance associated with excision of incorporated nucleotide analogue inhibitors of HIV-1 reverse transcriptase.
PMID: 19372874
2007
Current opinion in HIV and AIDS
Abstract: M184V, L74V, and K65R that diminish the effects of thymidine analogue-associated mutations.
Abstract: SUMMARY: The non-thymidine analogue-associated mutations M184V, L74V, and K65R show incompatibilities with thymidine-analogue-associated mutations.
Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV.
PMID: 16421366
2006
The New England journal of medicine
Abstract: In none of the patients did the K65R mutation develop.
Virologic and enzymatic studies revealing the mechanism of K65R- and Q151M-associated HIV-1 drug resistance towards emtricitabine and lamivudine.
Abstract: Finally, we studied the incorporation of these deoxycytidine analogues into a HIV-1 genomic DNA/DNA primer/template by K65R HIV-1 RT to address certain concerns associated with DNA sequence specificity.
Abstract: In this study, we measured the antiviral activity of FTC and 3TC against HIV-1 containing K65R, Q151M, and K65R/Q151M mutations.
Abstract: Overall, this study demonstrated that K65R and K65R/Q151M related drug resistance to FTC and 3TC was mainly due to a significant decrease in the rate of incorporation.
Abstract: The double mutation K65R/Q151M has been shown to be more resis
Clinical and genotypic correlates of mutation K65R in HIV-infected patients failing regimens not including tenofovir.
Abstract: Although its prevalence is increasing with the use of this drug, clinical and genotypic correlates of K65R occurrence have yet to be fully identified.
Abstract: Among genotypic correlates, the presence of M184V and NAMs seems to be protective for the emergence of K65R, while a strong positive correlation was found with the Q151M complex mutation.
Abstract: Moreover, the L100I mutation was independently associated with a higher probability of presenting K65R.
Abstract: Out of 1392 GRT performed for 771 patients, 12 TDF-naive patients had the K65R mutation with an overall prevalence of 1.6%.
Abstract: Previous AIDS, the use of abacavir, and treatment with efavirenz at GRT were ind