Prevalence of M184V and K65R in proviral DNA from PBMCs in HIV-infected youths with lamivudine/emtricitabine exposure.
PMID: 33734374
2021
The Journal of antimicrobial chemotherapy
Abstract: METHODS: We included vertically HIV-infected youths/young adults aged >=10 years in the Madrid Cohort of HIV-1 Infected Children and Adolescents, exposed to lamivudine and/or emtricitabine, with M184V/I and/or K65R/E/N in historic plasma samples, on antiretroviral therapy (ART), virologically suppressed (HIV-1 RNA <50 copies/mL), and with available PBMCs in the Spanish HIV BioBank.
Abstract: OBJECTIVES: We analysed the prevalence of M184V/I and/or K65R/E/N mutations archived in proviral DNA (pDNA) in youths with perinatal HIV, virological control and who previously carried these resistance mutations in historic plasma samples.
Introduction: As a consequence, they have a higher risk of selecting and accumulating
A Novel High Throughput, Parallel Infection Assay for Determining the Replication Capacities of 346 Primary HIV-1 Isolates of the Zurich Primary HIV-1 Infection Study in Primary Cells.
Method: AS-PCR was performed using primers IN_K65_fw (5'-TCCAGTATTTGCCATAAAGIA-3') or IN_K65R_fw (5'-CCAGTATTTGCCATAAAGIG-3'), and pol_3206_rv (5'-TTTGTCTGGTGTGGTAAATCCCCAC-3').
Method: Based on viral copy numbers of each variant, the replication capacity percentages were calculated to determine the competition kinetics of HIV-1 JR-CSFWT and HIV-1 JR-CSFK65R_M184V.
Method: The K65R and M184V mutations were introduced into the pJR-CSFWT plasmid using the QuikChange XL Site-Directed Mutagenesis Kit (Agilent Technologies, Inc., Santa Clara, CA, USA) with sdm_M184V_fw (5'-CCAGACATAATTATCTATCAATACGTGGATGATTTGTATGTAGGATCTG-3'), sdm_M184V_rv (5'-CAGATCCTACATACAAATCATCCACGTATTGATAGATAATTATGTCTGG-3'), sdm_
Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation.
PMID: 33315694
2021
Journal of acquired immune deficiency syndromes (1999)
Method: Key exclusion criteria included presence of NRTI resistance mutations K65R, T69 insertion, K70E, or Q151M mutation complex and any primary integrase strand transfer inhibitor or protease inhibitor (PI) resistance mutations.
High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat.
Result: For NRTIs, these were M184VI (55.6%), T215SNY (22.2%), and K65R (18.5%).
Result: Same for patients 310A, 1181A, and 309A who carried K65R and Y115F strains while on AZT.
Table: K65R
Discussion: Despite their small number, the 3 study patients with TAMs while on TDF and, another K65R and Y115F while on AZT hint that PDR to NRTI circulates in our study population.
Discussion: Tang et al in their meta-analysis found that NVP increases the risk of TAMs and K65R, which potentially confers high-level DR to AZT and TDF, respectively.
Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance.
Method: Tenofovir-associated mutations were defined as A62V, K65R/N/E, S68G/N/D, T69 deletions, and K70E/Q/N/T/S/G.
Result: Five SDRMs increased in prevalence among NRTI-experienced persons including K65R, K70E, Y115F, and M184V/I.
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.
Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil.
PMID: 34069929
2021
International journal of molecular sciences
Abstract: Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in
Method: All sequences having the K65R were separated by subtype and used to query local and public databases to identify highly related HIV-1 sequences.
Method: Minimum spanning network analysis of the sequences identified in transmission clusters with more than one K65R mutant was performed with PHYLOViZ.
Method: Phylogenetic Analysis of K65R Sequences and Transmission Clusters.
Method: The wildtype sequence (NPYNTPVFAIKKKDSTKWRKLVD) and the sequence with the K65R mutation (NPYNTPVFAIKRKDSTKWRKLVD) were used to generate all possible peptides sequences overlapping position 65 and ranging from eight to 12 amino acids.
Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study.
Result: M184 V/I 87 (28.8%), K65R/E/N 27 (8.9%), L74 V 3 (1.0%), and Y115F 12 (4.0%) were the mutations conferring resistance to NRTIs, along with thymidine analog mutations (TAMs) M41L 14 (4.6%), D67N 17 (5.6%), K70R 20 (6.6%), L210W
Result: K65R/E/N and K70E mutations conferred resistance to TDF and M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E conferred resistance to AZT.
Development of Human Immunodeficiency Virus Type 1 Resistance to 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine Starting with Wild-Type or Nucleoside Reverse Transcriptase Inhibitor-Resistant Strains.
PMID: 34516245
2021
Antimicrobial agents and chemotherapy
Abstract: To study EFdA resistance patterns that may emerge in naive or tenofovir (TFV)-, emtricitabine/lamivudine (FTC/3TC)-, or zidovudine (AZT)-treated patients, we performed viral passaging experiments starting with WT, K65R, M184V, or D67N/K70R/T215F/K219Q HIV-1.
Correlation of HIV-1 drug resistant mutations and virologic failure.
PMID: 34584606
2021
The Pan African medical journal
Introduction: These mutations included M184V, K65R,D67N,K70R,K219Q,Q151M, T215F, M41L, T69N, V75M, M41L, T69N, V75M, D67G, V75M, M184I, T215N, M41LM, T215N, K219N,210W, T215Y as NRTIs; K103N/S
HIV mutation literature information.
PMID: 
2021
The Journal of antimicrobial chemotherapy
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