From antiretroviral therapy access to provision of third line regimens: evidence of HIV Drug resistance mutations to first and second line regimens among Ugandan adults.
Conclusion: The observed PI resistance mutations (V82A, V82F, V82S, M46I, M46L and I54V) are clinically significant because they are associated with highest levels of phenotypic resistance and/or strongest evidence for interfering with successful PI therapy.
Table: M46I/L
Table: M46L
HIV-1 Transmitted Drug Resistance Mutations in Newly Diagnosed Antiretroviral-Naive Patients in Turkey.
PMID: 26414663
2016
AIDS research and human retroviruses
Abstract: Nonnucleoside reverse transcriptase inhibitor-associated TDRMs were detected in 3.3% (44/1,306) of patients (L100I, K101E/P, K103N/S, V179F, Y188H/L/M, Y181I/C, and G190A/E/S) and TDRMs to protease inhibitors were detected in 2.3% (30/1,306) of patients (M46L, I50V, I54V, Q58E, L76V, V82A/C/L/T, N83D, I84V, and L90M
Characteristics of Transmitted Drug-Resistant HIV-1 in Recently Infected Treatment-Naive Patients in Japan.
PMID: 26428230
2016
Journal of acquired immune deficiency syndromes (1999)
Abstract: Common mutations in both groups were M46I/L and T215 revertants.
Abstract: The phylogenetic clustering of cases with M46I/L or T215 revertants suggests that HIV with these mutations have become circulating strains.
Prevalence of transmitted HIV-1 drug resistance among young adults attending HIV counselling and testing clinics in Kigali, Rwanda.
Abstract: Two participants (4%) had the K103N non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation and one (2%) had the M46L protease inhibitor (PI) mutation.
Unique Flap Conformation in an HIV-1 Protease with High-Level Darunavir Resistance.
Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme.
Abstract: Three of five mutations in PR(S17) correlating with major drug resistance, M46L, G48V, and V82S, and five of 11 natural variations differ from the mutations in two clinically derived extreme mutants, PR20 and PR22 bearing 19 and 22 mutations, respectively.
Result: Mutations in PRS17 associated with resistance to multiple drugs are M46L, G48V, I54V, V82S and L90M.
Evolutionary Dynamics and Complicated Genetic Transmission Network Patterns of HIV-1 CRF01_AE among MSM in Shanghai, China.
Result: Only 2 networks for M46L, 6 networks for T69N, and 1 network for P225H were found in lineage 1C and 1B, lineage 1D, 1B, 1 A, small lineage, lineage1D, and lineage 1D, respectively.
Result: Overall, four main network-related drug resistant mutations (some were non-tansmitted drug resistance mutations) were discovered at V179D/E (n = 53), M46L (n = 15), T69N (n = 8), and P225H (n = 2).
HIV-1 Antiretroviral Drug Resistance Mutations in Treatment Naive and Experienced Panamanian Subjects: Impact on National Use of EFV-Based Schemes.
Result: For PIs, the most frequent ADR-CRM were M46IL (3.6%), V82AT (3.2%), L90M (2.6%) and Q58E (2.1%) and, the only SDRM observed was M46L/I (1.5%) (Fig 1C).
Result: Mutations associated with PIs were more observed at position M46IL an
Discussion: Our mutation pattern analyses showed that the most frequent SDRM were: K103N (4.0%) and P225H (2.0%) for NNRTIs, T215 revertants (2.4%) and M41L (2.0%) for NRTIs, and M46L/I (1.2%) for PIs.
Structural Studies of a Rationally Selected Multi-Drug Resistant HIV-1 Protease Reveal Synergistic Effect of Distal Mutations on Flap Dynamics.
Abstract: Flap mutations M46L and G48V in PRS17/DRV complex alter the Phe53 conformation by steric hindrance between the side chains.
Result: Conformational changes associated with mutation cluster of M46L, G48V and I54V are illustrated in Fig 4.
Result: Curling of flaps by mutations M46L, G48V and I54V.
Result: However, comparison of structures shows that the conformation of M46L mutation in PRS17/DRV complex differs from that observed in the DRV complex with M46L single mutant (PDB id: 2HS2).
Result: In addition, the Calpha atoms of
Global HIV-1 transmitted drug resistance in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.
Abstract: The most frequent TDR mutations observed were M41L, D67N/G/E, T215F/Y/I/S/C/D/E/V/N, 219Q/E/N/R, K103N/S, and G190A/S/E in reverse transcriptase, and M46I/L and L90M in protease.
Result: Similarly, M46IL (42%; 22/52) and L90M (25%; 13/52) were the most common PI mutations.
Discussion: Overall, transmitted protease resistance mutations were identified less frequently, with M46IL and
HIV mutation literature information.
PMID: 
2016
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