Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO).
Abstract: Baseline next-generation sequencing detected lamivudine resistance mutations (M184V/I and/or K65R/E/N) over a 5% threshold in 15/21 (71 4%) and 3/20 (15%) of participants with and without history of lamivudine resistance, respectively.
Introduction: This is the first clinical trial specifically designed to address the efficacy of lamivudine and dolutegravir as dual therapy for maintenance of viral suppression in patients with historical lamivudine resistance as long as M184V/I and/or K65R/E/N mutations are not found on proviral DNA population sequencing prior to dual therapy initiation.
Method: We compared the frequency of resistance mutations detected by next-generation sequencing and proviral bulk genotyping, and we analyzed the percentage of participants with M184V/I
Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) From Dolutegravir (DTG)+F/TAF or DTG+F/Tenofovir Disoproxil Fumarate (TDF) in the Presence of Pre-existing NRTI Resistance.
PMID: 32701823
2020
Journal of acquired immune deficiency syndromes (1999)
Abstract: RESULTS: In total, 83% (470/565) of participants had baseline genotypic data available with NRTI-R detected in 24% (138/565), including 5% (30/565) with K65R/E/N or >=3 thymidine analog mutations and 19% (108/565) with other NRTI-R mutations.
Switching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I.
PMID: 31430369
2019
The Journal of antimicrobial chemotherapy
Method: Primary NRTI-R substitutions were M41L, K65R/E/N, D67N, T69 insertions, K70E/R, L74V/I, Y115F, Q151M, M184V/I, L210W, T215Y/F and K219E/Q/N/R in RT.
Mutations in the reverse transcriptase and protease genes of human immunodeficiency virus-1 from antiretroviral naive and treated pediatric patients.
Result: Two ART treated patients, AIIMSU30 (D67E and L74Y) and AIIMSU52 (K65E and D67G) had two mutations in the RT gene, known to confer resistance to NRTI drugs.
Table: K65E
Genetic Characteristics of CRF01_AE Among Newly Diagnosed HIV-1-Infected 16- to 25-Year Olds in 3 Geographic Regions of Guangxi, China.
Result: Two TDR mutations, M46I (2) and I50V (1) were found in the protease region, and the other eight TDR mutations, K65E(1), D67N(1), T69N(1), K103N(1), Y181C(2), G190E(1), L210W(1), and P225H(1) were from the reverse transcriptase fragment.
The lysine 65 residue in HIV-1 reverse transcriptase function and in nucleoside analog drug resistance.
Introduction: Other substitutions have been described (K65E and K65N), but are much less common than K65R.
Frequency of Antiretroviral Resistance Mutations among Infants Exposed to Single-Dose Nevirapine and Short Course Maternal Antiretroviral Regimens: ACTG A5207.
PMID: 26525108
2014
Journal of AIDS & clinical research
Method: The primers for K65R ASP were, K65wt 5'-CTCCARTATTTGCCATAAAACA-3', K65R 5'-CTCCARTATTTGCCATAAAACG-3' and K65REV 5' TATTCCTAATTGAACYTCCCA-3'.
2014 Update of the drug resistance mutations in HIV-1.
Abstract: The following mutations have been added to existing classes or drugs: K65E/N has been added to the bars for the nucleoside and nucleotide analogue reverse transcriptase inhibitors (nRTIs) abacavir, didanosine, emtricitabine, lamivudine, stavudine, and tenofovir; L100I has been added to the bar for the nonnucleoside analogue reverse transcriptase inhibitor (NNRTI) rilpivirine; and F121Y has been added to the bars for the integrase strand transfer inhibitors (InSTIs) dolutegravir, elvitegravir, and raltegravir.
Discussion: Patient-derived viruses with K65E and site-directed mutations replicate very poorly in vitro; as such,
Identification of a rare mutation at reverse transcriptase Lys65 (K65E) in HIV-1-infected patients failing on nucleos(t)ide reverse transcriptase inhibitors.
PMID: 23749955
2013
The Journal of antimicrobial chemotherapy
Abstract: METHODS: Clinical and virological characteristics of patients harbouring the K65E mutation were analysed
Abstract: Structural analysis of the K65E RT mutant complex was performed by means of docking simulations.
Abstract: The molecular recognition of RT containing K65E supports evidence for the role of this mutation in resistance to tenofovir.
Abstract: The replication capacity was assessed using viruses harbouring the K65E mutation introduced by site-directed mutagenesis (SDM) in pNL 4-3.
Abstract: This study should have significant clinical implications, as these findings warn clinicians that other minor substitutions at Lys65 (such as K65E) play a role in NRTI resistance.
Mutational analysis of Lys65 of HIV-1 reverse transcriptase.
Abstract: In order to biochemically define the function of RT Lys(65), we have used site-specific mutagenesis to generate RT with a variety of substitutions at this position, including K65E, K65Q, K65A and K65R.
Abstract: In particular, Glu in K65E can form a salt bridge with Arg(72), leading to the diminution of the latter residue's interaction with the alpha-phosphate of the dNTP residue.
Abstract: The pH optimum for the DNA polymerase activity of K65E RT was 6.5, compared to 7.5 for the wild-type enzyme, and 8.0 for the K65R, K65A and
HIV mutation literature information.
PMID: 
2020
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