Abstract: Most common mutations were M184V (57.1%), Y188C (25.7%), M46I/L (25.7%) and V82A/M (25.7%).
Drug Resistance Mechanism of M46I-Mutation-Induced Saquinavir Resistance in HIV-1 Protease Using Molecular Dynamics Simulation and Binding Energy Calculation.
Result: A decrease in the Asp25-Ile50 distance up to the non-mutated system levels at most of the simulation period indicates an inward (towards core of the active site) curling of the flap in the M46I mutation systems.
Result: A significant decrease in van der Waals contribution in the SQ-MI complex indicates an important role of the M46I mutation in decreasing the interaction between saquinavir and HIV 1 protease binding.
Result: An increased SASA value in the M46I HIV-1 protease structure in comparison to the wild-type protease might be due to the conformational flexibility in the protein.
Result: Based on these facts, our results indicate that WT and SQ-WT showed closed-flap conformation (<1.72 nm), and the
Reverse transcriptase and protease inhibitors mutational viral load in HIV infected pregnant women with transmitted drug resistance in Argentina.
PMID: 34085506
2021
Revista espanola de quimioterapia
Abstract: Most frequent PI-RAMs were I85V, M46I, I50V and L90M (n=2, 5% each).
Result: Most frequent PI-RAMS were I85V, M46I, I50V and L90M (n=2, 5% each), all of them with modest impact in the activity of currently available PIs.
Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study.
Abstract: Using the 2% detection threshold, individual DRMs with the highest prevalence were: PI M46IL (5.5%), RT K103NS (3.5%), RT G190ASE (3.1%), T215ISCDVEN (2.5%), RT M41L (2.2%), RT K219QENR (1.7%) and PI D30N (1.6%).
Result: Estimates of PI TDR are strongly influenced by the M46IL mutation, which was observed in 5.5% of all samples, mostly as low-level v
Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil.
PMID: 34069929
2021
International journal of molecular sciences
Result: SDRM in PR were found in 5021 (24.82%) sequences and the more frequent were V82A (9.99%, n = 2021), M46I (9.58%, n = 1938), and I54V (8.50%, n = 1719).
Result: The SDRM with most similar prevalence when comparing both groups were M46I, V82A, L90M and I54V.
Temporal Trends in HIV-1 Mutations Used for the Surveillance of Transmitted Drug Resistance.
Discussion: However, M46I remains an important DRM for lopinavir and atazanavir, although it may continue to occur at minimally elevated levels in the aforementioned subtypes.
Discussion: The potential for M46I/L to occur at low levels in subtype A and CRF01_AE populations without previous PI exposure was recognized at the time the 2009 SDRM list was developed and in several subsequent analyses.
Acquired HIV-1 Protease Conformational Flexibility Associated with Lopinavir Failure May Shape the Outcome of Darunavir Therapy after Antiretroviral Therapy Switch.
Abstract: The HIV-1 protease variants were from clinical isolates with a combination of drug resistance mutations; MUT-1 (M46I, I54V, V82A, and L10F), MUT-2 (M46I, I54V, L76V, V82A, L10F, and L33F), and MUT-3 (M46I, I54V, L76V, V82A, L90M, and F53L).
Introduction: Research has shown that the most reported major HIV-1 PI resistance mutations in patients failing second-line the
Drug resistance mutations in HIV provirus are associated with defective proviral genomes with hypermutation.
Abstract: Certain Apolipoprotein B Editing Complex 3-related DRMs including reverse transcriptase gene mutations M184I, E138K, M230I, G190E and protease gene mutations M46I, D30N were enriched in hypermutated sequences but not in intact sequences or plasma sequences.
Prevalence and factors associated with HIV-1 drug resistance mutations in treatment-experienced patients in Nairobi, Kenya: A cross-sectional study.
HIV mutation literature information.
PMID: 
2022
HIV medicine
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