Introduction: Genetic resistance pathways including primary mutations at codons Y143C/H/R, Q148H/K/R or N155H together with one or more additional associated secondary mutations at L74M, E92Q, T97A, E138E/A/K or G140S/A, has been reported to result in higher levels of resistance with RAL treatment.
Table: G140A
Discussion: Another simulation study also revealed the binding mode of EVG and RAL to HIV-1 IN and the structural mechanism of drug resistant mutants (G140A and G149A) that affect the 140's loop region spanning residu
HIV-1 integrase drug-resistance mutations in Iranian treatment-experienced HIV-1-infected patients.
Abstract: The DRMs that were identified belonged to the INSTI class, including E138K, G140A, S147G, and Q148R.
Integrase strand transfer inhibitor (INSTI)-resistance mutations for the surveillance of transmitted HIV-1 drug resistance.
PMID: 31617907
2020
The Journal of antimicrobial chemotherapy
Abstract: Among the 29 relatively common INSTI-selected mutations, 24 emerged as candidates for inclusion on a list of INSTI surveillance drug-resistance mutations: T66A/I/K, E92G/Q, G118R, F121Y, E138A/K/T, G140A/C/S, Y143C/H/R/S, S147G, Q148H/R/K, N155H, S230R and R263K.
Predicted antiviral activity of tenofovir versus abacavir in combination with a cytosine analogue and the integrase inhibitor dolutegravir in HIV-1-infected South African patients initiating or failing first-line ART.
PMID: 30380053
2019
The Journal of antimicrobial chemotherapy
Discussion: We did observe Q148R, which is associated with high-level dolutegravir resistance when accompanied by the G140S/A mutations.
Dolutegravir Monotherapy of Simian Immunodeficiency Virus-Infected Macaques Selects for Several Patterns of Resistance Mutations with Variable Virological Outcomes.
Abstract: Some mutations, such as G118R, previously shown to severely impair the replication capacity in vitro, were associated with more sustained virological and immunological benefits of continued DTG therapy, while other mutations, such as E92Q and G140A/Q148K, were associated with more variable outcomes.
Prevalence and determinants of resistance mutations in HIV-1-infected patients exposed to integrase inhibitors in a large Italian cohort.
Abstract: Overall, the Q148H/K/R plus G140A/C/S and/or E138A/K/T pattern, defining an intermediate level of resistance to DTG, was detected in 70 (15%) cases.
Abstract: The most frequent INSTI resistance mutation was N155H, followed by Q148H/K/R, G140A/C/S, E138A/K/T and Y143C/H/R.
Development of the R263K Mutation to Dolutegravir in an HIV-1 Subtype D Virus Harboring 3 Class-Drug Resistance.
PMID: 30648124
2019
Open forum infectious diseases
Introduction: DTG appears to have a high genetic barrier to resistance, unlike the other drugs within the INSTI class, raltegravir and elvitegravir, which select for major resistance mutations such as N155H, Y143H/R/C, G140A/S, and Q148H/R/K.
High predictive efficacy of integrase strand transfer inhibitors in perinatally HIV-1-infected African children in therapeutic failure of first- and second-line antiretroviral drug regimens recommended by the WHO.
PMID: 30891603
2019
The Journal of antimicrobial chemotherapy
Discussion: However, polymorphism at position 140, similar to that observed in our study (G140K/R), has been described as leading to a higher genetic barrier for non-B subtypes to acquire the usual accessory INSTI-selected DRMs G140A/C/S at this position.
Discussion: Indeed, at position 140, the usual INSTI-selected accessory mutations are G140A/C/S, which are associated with a 3- to 5-fold reduction in susceptibility to elvitegravir when they occur alone.
Drug resistance emergence in macaques administered cabotegravir long-acting for pre-exposure prophylaxis during acute SHIV infection.
Discussion: The impact of G140R in HIV is not known although other non-polymorphic mutations at position 140 including G140S/A/C are associated with 10-100-fold reduced susceptibility of HIV to RAL, EVG, and DTG.
Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia.
Result: According to the Stanford Genotypic Resistance Interpretation Algorithm, v8.8 all TDR mutations that we identified were clinically relevant except mutation T69D, while the International AIDS Society (IAS) list confirmed nearly all mutations, except T215S, K219R, G190E and G140A, as clinically relevant.
Result: Resistance to integrase strand-transfer inhibitors (InSTIs) was detected in single person, G140A, 1% (1/100).
Result: Some of these sequences carrying SDRMs: T69D, G190E, K219Q and K219R +
HIV mutation literature information.
PMID: 
2020
PloS one
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