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.
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
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_
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.
HIV-1 Drug Resistance and Genetic Transmission Networks Among MSM Failing Antiretroviral Therapy in South China 2014-2019.
Abstract: The most common DRMs were M184I/V (42.2%), followed by V179D/E (37.9%) and K65R (27.2%).
Result: Among the NRTI DRMs, M184I/V (42.2%, 166/393) was the most frequent, followed by K65R (27.2%, 107/393).
Result: The most common NRTI mutation pattern was M184V+K65R, with a frequency of 15.0% (59/393).
Table: K65R
Discussion: A high frequency of K65R plus M184V/I (15.0%) was observed in this study, and K65R plus M184 V/I appeared sufficient t
Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study.
PMID: 34397746
2021
Journal of acquired immune deficiency syndromes (1999)
Method: Participants had an estimated glomerular filtration rate (eGFR) >=50 mL per minute (calculated by the Cockcroft-Gault equation) and no documented history of resistance to INSTIs or tenofovir (TFV) resistance defined as K65R/E/N mutations, >=3 thymidine analog mutations, or T69 insertions (See Appendix, Supplemental Digital Content, http://links.lww.com/QAI/B674).
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.
Nucleoside Reverse-Transcriptase Inhibitor Resistance Mutations Predict Virological Failure in Human Immunodeficiency Virus-Positive Patients During Lamivudine Plus Dolutegravir Maintenance Therapy in Clinical Practice.
PMID: 34327247
2021
Open forum infectious diseases
Method: The role of any non-TAM was not specifically studied because of the low number of patients harboring the K65R/E/N mutation (the only other non-TAM associated with decreased susceptibility to 3TC) and its collinearity with M184V/I.
HIV mutation literature information.
PMID: 
2021
HIV medicine
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