Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study.
PMID: 34694877
2022
Antimicrobial agents and chemotherapy
Result: One participant (participant 1) had the integrase substitution R263R/K and NRTI resistance-associated substitutions K65R and M184I/V at baseline, despite no apparent prior INSTI treatment, but did not demonstrate in vitro dolutegravir phenotypic resistance.
Table: K65R
Transmitted Drug Resistance Among Human Immunodeficiency Virus (HIV)-1 Diagnoses in the United States, 2014-2018.
Abstract: Continued population-level monitoring of INSTI and NRTI mutations, especially M184V and K65R, is warranted amidst expanding use of second-generation INSTIs and PrEP.
Abstract: Most individual mutations had a prevalence <1.0% including M184V (0.9%) and K65R (0.1%); K103N was most prevalent (8.6%).
Drug Resistance Mutations in a Population Before Antiretroviral Therapy Initiation in Northern South Africa.
PMID: 34107774
2022
AIDS research and human retroviruses
Abstract: The most frequent SDRMs based on drug class were; K103N (7.9%-NNRTI), K65R (2.5%-NRTI), and D30N (0.8%-PI).
HIV-1-infection in a man who has sex with men despite self-reported excellent adherence to pre-exposure prophylaxis, the Netherlands, August 2021: be alert to emtricitabine/tenofovir-resistant strain transmission.
Abstract: Sequencing identified resistance-associated mutations (RAM) M184V and K65R, conferring resistance to emtricitabine and tenofovir, and RAM V108I and E138A.
Discussion: A combination of RAM similar to those found in this case (M184V, K65R, V108I and E138A) has not been reported in PrEP users.
Discussion: Although theoretically possible, it is unlikely that the short-term and limited drug exposure was sufficient to select for both M184V and K65R, with only few M184V mutations, and even more rarely K65R, described in the literature.
Discussion: However
High Rate of HIV-1 Drug Resistance in Antiretroviral Therapy-Failure Patients in Liaoning Province, China.
PMID: 35229630
2022
AIDS research and human retroviruses
Abstract: K65R (29.69%), M184V (28.52%) were the most common NRTIs resistance mutations.
HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China.
Result: K65R was the most common low-frequency DRM with frequencies between 1% and 9%, concentrated at frequencies from 2% to 5%.
Result: It is interesting that this low-frequency K65R mutation is significantly unevenly distributed among subtypes; 5.7% (2/35) in CRF01_AE, when compared with 95.1% (58/61) in CRF07_BC and 93.1% (54/58) in CRF08_BC (p < 0.001).
Result: Moreover, K65R was still the most common low-frequency mutation at the follow-up.
Result: Within a year, some minority DRMs at frequencies 1%-10% remained unchanged, including: PI-related D30N, M46LI, I54VT and N88D, NRTI-related K65R and
Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study.
Result: Finally, the frequency of tenofovir resistance was estimated to be 1.3% at the 20% threshold, 1.6% at the 5% threshold, and 2.4% at the 2% threshold, despite the complete absence of the K65R mutation.
Result: Notably, the K65R mutation was not observed in any sample, even at the 2% threshold.
Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa.
Conclusion: Using HTS-GRT, PI RAMs (V82A) and RTI RAMs (K65R, M184V or K103N) were identified in < 20% of the population that Sanger-based sequencing failed to identify, strengthening their role in detecting the acquired mutations early.
Result: Most of the DRMs in the minor viral quasispecies were observed in V82A mutation (n = 13) in protease and K65R (n = 5), K103N (n = 7) and M184V (n = 5) in reverse transcriptase.
Long-term efficacy of dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: Week 96 results of ART-PRO pilot study.
PMID: 33200210
2021
The Journal of antimicrobial chemotherapy
Abstract: Baseline proviral DNA NGS detected lamivudine RAMs (M184V/I and/or K65R/E/N) above a 5% threshold in 71.4% (15/21) and 15% (3/20) of participants with and without history of lamivudine resistance, respectively.
Tenofovir disoproxil fumarate and emtricitabine maintenance strategy in virologically controlled adults with low HIV-1 DNA: 48 week results from a randomized, open-label, non-inferiority trial.
PMID: 33724373
2021
The Journal of antimicrobial chemotherapy
Abstract: Six VFs occurred in the tenofovir disoproxil fumarate/emtricitabine arm (two with emerging mutations M184V and K65R) versus two in the control arm (ITT difference 3.5%, 95% CI -1.9 to 9.4).
HIV mutation literature information.
PMID: 
2022
Antimicrobial agents and chemotherapy
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