Low Frequency of Integrase Inhibitor Resistance Mutations Among Therapy-Naive HIV Patients in Southeast China.
PMID: 33679129
2021
Drug design, development and therapy
Discussion: E157Q has been shown to act as a compensatory mutation due to its ability to restore damaged enzymatic activity caused by N155H or R263K substitution.
Transmitted HIV drug resistance and subtype patterns among blood donors in Poland.
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 R263R/K, V260I, R263R, N155H, G118R, and E138E.
Method: The mutations of interest included: T66A/I/K, Discussion: Compared with a similar cohort of patients from clinical trials, the selection of major integrase DRM- R263K was common.
Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations.
Abstract: RESULTS: We observed 12.8% (37/287) sequences to contain RAMs, with only 1.0% (3/287) of the sequences having major INSTI RAMs: T66A, Q148H, R263K and N155H.
Abstract: The interaction analysis revealed that DTG bound to DNA, 2MG ions and DDE motif residues for T66A, T97A, Q148H, N155H and R263K comparable to the WT structure.
Table: R263K
Figure: f R263K HIV-1 CRF02_AG IN showing in total four contacts formed between DTG and one IN residue, one DNA nucleotide and two MG ion
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.
Altered HIV-1 mRNA Splicing Due to Drug-Resistance-Associated Mutations in Exon 2/2b.
PMID: 35008581
2021
International journal of molecular sciences
Result: Additionally, R263K was recently described to decrease HIV integration and to be associated with therapy failure using Dolutegravir in HIV-1 treated patients.
Result: As expected from the HEXplorer prediction, the silent R263R mutation led to a similar splicing pattern as R263K, albeit, in contrast to the missense version R263K, a slight band for the most abundant mRNA species Tat2b was still present (Figure 3C).
Result: Compared with the parental sequence, the V260I mutation is predicted to have little effect on splice site recognition with a DeltaHZEI of -37.79, whereas R263K is predicted to result in a more severe change in splicing outcome with a DeltaHZEI of -132.16.
Result: For R263K, a similar pattern was observed,
HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020.
Result: Resistance in IN was mainly due to R263K (1.6%) and E138AKT, G140ACS, Q148HKR (0.8% each) (Figure 6c).
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: One mutation of particular interest is the R263K (INI) mutation, which confers low-level (<3-fold reduced susceptibility) resistance to DTG and BIC and is associated with diminished HIV DNA integration and viral fitness.
Discussion: The M184V (RT) mutation was detected after 17 weeks of therapy, and at week 37 the R263KR (INI) mutation was detected via bulk sequencing (Viracor Lab, Misso
Discussion: Two other reported cases of the R263KR (INI) mutation have been in individuals with non-subtype B HIV type 1, both with advanced HIV disease, one in a treatment-experienced individual and another under first-line treatment with BIC/FTC/TAF.
A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing.
Introduction: Although these mutations: IN:M50I, RH:N79S and IN:S17N, were reported NOPs mutations, we presumed that a particular ART might facilitate the emergence of the mutations and affect susceptibility to integrase inhibitor, since IN:M50I is reported as a mutation associated with resistance to dolutegravir (DTG), which enhances resistance of a mutant carrying R263K mutation to DTG, but not resistance to the drug by itself.
HIV mutation literature information.
PMID: 
2021
Drug design, development and therapy
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