Result: All 3 participants who had genotype testing showed RAMs; two had isolated RAMs (one E138K and the other Y181C), and the third had multiple RAMs (V75I, E138K, Y181C, M184I, K219E, and M230L).
Discussion: In the DUET studies, however, participants all had at least one baseline NNRTI mutation and treatment-emergent mutations at position E138 in the reverse transcriptase enzyme were also observed, in addition to the more frequent V179F/I and Y181C mutations.
Synthesis and Antiviral Evaluation of 1-[(2-Phenoxyethyl)oxymethyl] and 6-(3,5-Dimethoxybenzyl) Analogues of HIV Drugs Emivirine and TNK-651.
Abstract: The newly synthesized non-nucleosides were tested for antiviral activity against wild type HIV-1 IIIB as well as the resistant strains N119 (Y181C), A17 (K103N+Y181C), and the triple mutant EFV(R) (K103R+V179D+P225H) in MT-4 cells.
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
Assessment of etravirine resistance in HIV-1-infected paediatric patients using population and deep sequencing: final results of the PIANO study.
Abstract: Baseline minority etravirine RAMs (n) were detected in 8/40 VFs (V90I [2], A98G [1], L100I [1], V106I [1], E138G [1] and Y181C [2]) and 5/38 responders (V90I [3], A98G [1], V106I [1] and E138G [1]).
Abstract: The most frequent emerging non-nucleoside reverse transcriptase inhibitor RAMs detected by PS (>=3 VFs; n) were the etravirine RAMs Y181C (8), V90I (3), L100I (3) and E138A (3).
An in-silico approach aimed to clarify the role of Y181C and K103N HIV-1 reverse transcriptase mutations versus Indole Aryl Sulphones.
PMID: 26650686
2016
Journal of molecular graphics & modelling
Abstract: The effects of two of the most clinically relevant RT mutations (Y181C; K103N) were studied by a computational approach.
Sub-Epidemics Explain Localized High Prevalence of Reduced Susceptibility to Rilpivirine in Treatment-Naive HIV-1-Infected Patients: Subtype and Geographic Compartmentalization of Baseline Resistance Mutations.
PMID: 26651266
2016
AIDS research and human retroviruses
Method: Evidence of transmitted HIV-1 drug resistance (TDR) was defined by the presence of at least one surveillance drug resistance mutation (SDRM) from the consensus genotypic definition of Bennett et al., including major RVP-RAMs L100I+K103N, Y181C/I/V, Y188L, and M230L, and minor RPV-RAMs L100I, K103S, V106A,
Result: Evidence of transmitted drug resistance was observed in 401 patients (8.7%), with RPV-RAMs Y181C, Y188L, K103S, V106A, V179F, and G190A/S detected as SDRMs.
Simplified Paper Format for Detecting HIV Drug Resistance in Clinical Specimens by Oligonucleotide Ligation.
Figure: Analysis of clinical specimens and plasmid standards by paper capture, denaturation, and detection (CDD) and plate CDD for mutations K103N and Y181C.
Figure: Comparison of paper Capture, Denaturation, and Detection (CDD) and plate CDD for analysis of a plasmid standard mixture series for mutation Y181C.
Figure: MUT and WT signals obtained by paper and plate CDD format OLA at codons K103N, Y181C, M184V and G190A from 26 clinical specimens were used to calculate MUT Ratios.
Discussion: Overall, the paper CDD showed analytical sensitivity comparable to the plate CDD for a plasmid mixture series (Y181C, Fig 3 & S4I Fig), and results for clinical specimens showed strong concordance across fou
Systematic review to determine the prevalence of transmitted drug resistance mutations to rilpivirine in HIV-infected treatment-naive persons.
Abstract: Two mutations were more prevalent: E138A/G/K/Q/R (0.7%, 95% CI 0.2, 1.3) and Y181C/I/V (0.3%, 95% CI 0.2, 0.4).
Ribonuclease H/DNA Polymerase HIV-1 Reverse Transcriptase Dual Inhibitor: Mechanistic Studies on the Allosteric Mode of Action of Isatin-Based Compound RMNC6.
Abstract: Enzymatic studies showed that RMNC6 interferes with efavirenz (an approved NNRTI) in its binding to the RT polymerase domain, although NNRTI resistance-associated mutations such as K103N, Y181C and Y188L had a minor impact on RT susceptibility to RMNC6.
Conclusion: This double-site binding mode seems to confirm that it could be possible to target both RT-associated functions by a single molecule, retaining full potency of inhibition on drug-resistant mutant RTs such as K103N, Y181C and Y188L.
Table:
Discovery of the Aryl-phospho-indole IDX899, a Highly Potent Anti-HIV Non-nucleoside Reverse Transcriptase Inhibitor.
PMID: 26804933
2016
Journal of medicinal chemistry
Abstract: Optimization of the phosphinate aryl substituent led to the discovery of the 3-Me,5-acrylonitrile-phenyl analogue RP-13s (IDX899) having an EC50 of 11 nM against the Y181C/K103N double mutant.
Abstract: Since a major problem associated with NNRTI treatment is the emergence of drug resistant virus, this work focused on optimization of the APhI against clinically relevant HIV-1 Y181C and K103N mutants and the Y181C/K103N double mutant.
HIV mutation literature information.
PMID: 
2016
Antiviral therapy
Browser Board
Co-occurred Entities
Filtrator
ViMRT