Result: In this study,19 substitutions conferring major resistance to DTG at 10 amino acid positions in the IN (T66A/I/K, E92G, G118R, E138K/A/T, G140S/A/C, Y143R/C/H, S147G, Q148H/R/K, N155H, and R263K) were assessed to explore the genetic barrier to DTG.
Result: No major DRMs known to be associated with DTG resistance (T66K, E92Q, G118R, E138K/A/T, G140S/A/C<
Integrase Strand Transfer Inhibitor (INSTI) Genotypic Resistance Analysis in Treatment-nNaive, INSTI Free Antiretroviral-Experienced and INSTI-Experienced Turkish Patients Infected with HIV-1.
Abstract: Additional mutations, E92Q, E138K, G140A, S147G, and Q148R were found in elvitegravir; E192Q, E138K/T, G140A/S, S147G, Q148H/R, N155H, E157Q were found in dolutegravir (DTG) experienced patients.
Spectrum of Activity of Raltegravir and Dolutegravir Against Novel Treatment-Associated Mutations In HIV-2 Integrase: A Phenotypic Analysis Using An Expanded Panel of Site-Directed Mutants.
PMID: 35134180
2022
The Journal of infectious diseases
Abstract: HIV-2-specific integrase mutations Q91R, E92A, A153G, and H157Q/S, which have not been previously characterized, significantly increased the EC50 for raltegravir when introduced into one or more mutational backgrounds; mutations E92A/Q, T97A, and G140A/S conferred similar enhancements of dolutegravir resistance.
Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials.
PMID: 34897227
2022
Journal of acquired immune deficiency syndromes (1999)
Table: G140A/C/S
Discussion: For example, the combination of Q148H/K/R and G140A/C/S in the presence of additional substitutions can cause high-level resistance to BIC (>10-fold change in phenotype compared with wild type) but as was seen with the naive case presented in this study, the Q148H+G140S pattern can also be susceptible to BIC.
Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study.
PMID: 34694877
2022
Antimicrobial agents and chemotherapy
Table: G140A/C/S
Case Report: Emergent Resistance in a Treatment-Naive Person With Human Immunodeficiency Virus Under Bictegravir-Based Therapy.
PMID: 34189182
2021
Open forum infectious diseases
Discussion: Resistance to RAL and EVG has been well-characterized in the literature with the accumulation of primary resistance substitutions along several pathways including the N155H, Q148, and G140A/G148R/H/Q pathways conferring high-level cross-resistance to RAL and EVG.
Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study.
Method: INSTI mutations, which are not included on this list, were defined as those on the Stanford HIVdb surveillance DRM list, namely T66AIK, E92Q, F121Y, G140ACS, Y143CHR, S147G, Q148HKR and N155HS.
Result: All individual INSTI DRMs were observed below the 20% threshold, with the exception of G140S (detected at the 25% level, sample from Spain collected in 2012) and G140A (21%, sample from Peru in 2011).
Discussion: The only INSTI DRMs detected above the 20% threshol
HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana.
Method: The mutations of interest included: T66A/I/K, E92Q, G118R, E138K/A/T, G140S/A/C, Y143R/C/H, S147G, Q148H/R/K, N155H and R263K.
Result: Amongst the individuals previously exposed to RAL ART (seven out of eleven), DRMs selected whilst failing their current DTG based regimens were E138K, G140A, Q148R; and N155H Figure 3.
Result: The four individuals failing DTG cART but with no documented prior exposure to RAL, their selected DRMs w
Virologic outcomes of switching to dolutegravir functional mono- or dual therapy with a non-cytosine nucleoside analog: a retrospective study of treatment-experienced, patients living with HIV.
Method: Patients with the following baseline mutations associated with reduced susceptibility to DTG: T66K, E92Q, G118R, E138 K/A/T, G140 S/A/C, Q148 H/R/K, N155H and R263K were excluded.
High-level resistance to bictegravir and cabotegravir in subtype A- and D-infected HIV-1 patients failing raltegravir with multiple resistance mutations.
PMID: 34453542
2021
The Journal of antimicrobial chemotherapy
Abstract: However, combinations of primary INSTI-resistance mutations such as E138A/G140A/G163R/Q148R or E138K/G140A/S147G/Q148K led to decreased susceptibility to both cabotegravir (fold change in EC50 values from 429 to 1000x) and bictegravir (60 to 100x), exhibiting a high degree of cross-resistance.
HIV mutation literature information.
PMID: 
2022
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