literature

Frequent cross-resistance to rilpivirine among subtype C HIV-1 from first-line antiretroviral therapy failures in South Africa.

PMID: 29566538 2018 Antiviral chemistry & chemotherapy

Method: Plasma samples contained a median of 3 [Q1-Q3: 2-4] NNRTI-associated drug resistance mutations which included A98G, L100I, K101E/H, K103N/S, V106M, V108I, E138A/K, V179D/E Y181C, Y188L/C, G190A, H221Y, P225H, F227L, and M230L.

Figure: FC resistance was evaluated based on the contribution of the number of RPV-associated mutations (L100I,

PMID: 30119633 2018 Retrovirology

Result: In contrast, the loss of T66I in 14624 was accompanied by the acquisition of L74M/E138K/S147G/M154IM and L74M/G140GS/S147G at week 27 with DTG and CAB, respectively.

Result: Resistance profiles associated with escape from EVG drug pressure were associated with T66I and the accumulation of major resistance including Q148R/K, E138K, and S147G.

Result: Selection of strain E78004 with CAB resulted in high level resistance along a Q148R/E138K/Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles.

PMID: 29635166 2018 European journal of medicinal chemistry

Conclusion: In general, a series of novel diarylnicotinamide triazole analogues were rationally designed based on structure-guided approach, synthesized and evaluated for their bioactivities against HIV-1 (IIIB, K103 N + Y181C, L100I, K103 N, E138K, Y181C, Y188L and F227L + V106A) and HIV-2 (ROD) in MT-4 cells.

Conclusion: Noteworthily, regarding the inhibitory activity against E138K, the major drug resistant mutant to the new generation HIV-1 NNRTIs, 3b8 and 3b9 with triazole linker targeting the entrance channel of NNRTIs in RT

Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir.

PMID: 30568974 2018 Open forum infectious diseases

Discussion: In an analysis of individual derived isolates with E138K, G140S, and Q148H, the FC to bictegravir is reported to be as high as 19-fold (2-19), whereas baseline DTG FC was 63 (3-63).

Discussion: In these cases, genotypic analysis revealed that T97A emerged in addition to other mutations, including E92E/Q, E138E/K, and N155H.

Characterization of minority HIV-1 drug resistant variants in the United Kingdom following the verification of a deep sequencing-based HIV-1 genotyping and tropism assay.

PMID: 30409215 2018 AIDS research and therapy

Result: Most of the minority mutations in viruses from both groups of naive patients were observed in the RT, e.g., M41L, E44D, A62V, K65R, D67N, D67G, V75I, L100I, K103N, K103R, V188I, M184I, L210W, K219Q, Y318F, etc., although a number of minority mutations associated with resistance to PI (L10F, V11I, M46I/

The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase.

PMID: 30174310 2018 Cell chemical biology

Discussion: EFdA also retained its potency against the viruses containing not only M184V/I mutation, but also E138K mutation, which caused virological failure during the clinical trials that evaluated rilpivarine with emtricitabine as a first-line therapy.

Detection of minority drug resistant mutations in Malawian HIV-1 subtype C-positive patients initiating and on first-line antiretroviral therapy.

PMID: 29977795 2018 African journal of laboratory medicine

Result: The common minority NNRTI mutations detected were V106M, V179T and G190A (3/20 each), followed by E138K and Y181C (2/20 each), and K101P, K103N, V108I, E138A, V179D, A190E and H221Y (1/20 each).

Table: E138K

Design, synthesis and biological evaluation of substituted (+)-SG-1 derivatives as novel anti-HIV agents.

PMID: 29699924 2018 Bioorganic & medicinal chemistry letters

Abstract: The result showed that RT- E138K/M184V mutant virus conferred 4.7-9.1-fold resistance to 4c, 4f, 2 and 6b, but only showed slight resistance to 4b (2-fold) which was better than SG-1.

HIV-1 strains belonging to large phylogenetic clusters show accelerated escape from integrase inhibitors in cell culture compared with viral isolates from singleton/small clusters.

PMID: 28472323 2017 The Journal of antimicrobial chemotherapy

Discussion: The emergence of select mutations under dolutegravir pressure, including R263K (AGA AAA or AGG AAG), G163R (GGA AGA or GGG AGG) and E138K (GAA AAA, GAG AAG), may be related to APOBEC-mediated G A hypermutation.

Drug-like property-driven optimization of 4-substituted 1,5-diarylanilines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors against rilpivirine-resistant mutant virus.

PMID: 28465101 2017 Bioorganic & medicinal chemistry letters

Abstract: Newly synthesized p-cyanovinyl-DAANs (8a-8g) with different R1 side chains plus prior active p-cyanoethyl-DAANs (4a-4c) were evaluated not only for anti-HIV potency against both wild-type HIV virus and rilpivirine-resistant (E138K, E138K+M184I) viral replication, but also for multiple drug-like properties, including aqueous solubility, lipophilicity, and metabolic stability in human liver microsomes and human plasma.

Abstract: This study revealed that both ester and amide R1 substituents led to low nanomolar anti-HIV potency against wild-type and rilpivirine-resistant viral strains (E138K-resistance fold changes<3).

Introduction: Furthermore, these same DAANs also inhibited the E138K+M184I viral strain with resistance FCs ranging from 1.4 to 6.3, better than or sim