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 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
Abstract: G118R or R263K increased the rate of dolutegravir dissociation from integrase-DNA complexes versus wild-type but retained prolonged binding.
Abstract: Treatment-emergent G118R was detected in 5 participants, occurring with >=2 other integrase substitutions, including R263R/K, in 3 participants and without other integrase substitutions in 2 participants.
Method: A similar procedure was used for the G118R mutant residue in chain C.
Method: For G118R residues in chains A and C, a localized Prime calculation was executed to optimize the interaction of G118R with both E92 and the 3' hydroxy of the tDNA terminal th
Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study.
PMID: 34694878
2022
Antimicrobial agents and chemotherapy
Discussion: In the larger adult phase III studies DAWNING and SAILING, emergence of G118R and/or R263K with dolutegravir occurred in <2% of participants.
Discussion: Of the 6 participants with PDVF and resistance to dolutegravir, 5 developed G118R.
Discussion: Of the adolescents and children with treatment-emergent INSTI resistance in the P1093 study, 6 of 8 with resistance had the integrase substitution G118R
Discussion: Treatment-emergent G118R in combination with either L74M or T66I was associated with reduced dolutegravir susceptibility compared with G118R alone or with E138E/K.
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: G118R
Could Long-Acting Cabotegravir-Rilpivirine Be the Future for All People Living with HIV? Response Based on Genotype Resistance Test from a Multicenter Italian Cohort.
PMID: 35207677
2022
Journal of personalized medicine
Method: We also excluded PWH with the following INSTI mutations: T66I, E92Q, G118R, G140S, Y143A/C/G/H/K/R/S, S147G, Q148H/K/N/R, N155H/S/T, and R263K.
High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort.
Result: The mutations conferring resistance to DTG, the newly introduced and WHO recommended INSTI, include E138K (IN), G118R, and R263K with prevalences of 6%, 3%, and 2%, respectively.
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-2ROD9 variants encoding G118R alone, or insertions of residues SREGK or SREGR at position 231, were resistant to both INIs.
Dolutegravir in the long term in children and adolescents: frequent virological failure but rare acquired genotypic resistance.
Abstract: Resistance to dolutegravir (mutations G118R and E138A in the integrase gene) emerged in one adolescent (0.7% of subjects, 2.3% of those with VF).
HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana.
Introduction: INSTI-naive highly treatment-experienced patients failing DTG cART have been found to have a virus with DRMs including G118R, D67N; H51H/Y, G118R, E138E/K, and less commonly
Result: The four individuals failing DTG cART but with no documented prior exposure to RAL, their selected DRMs were E138K, G140A, Q148K, A128T; G118R, E138K; N155ND and T66A, G118R, E138EAKT Figure 3.
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.
HIV mutation literature information.
PMID: 
2022
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