Short Communication: Integrase Strand Transfer Inhibitors Drug Resistance Mutations in Puerto Rico HIV-Positive Individuals.
PMID: 33800269
2021
International journal of environmental research and public health
Abstract: We identified the Q148HKR, G140S, Y143R, N155H, S147G, and E138EA major drug resistance mutations and the D232DN, T97TA, E157Q, G163GART accessory mutations.
Result: Interestingly, two samples, one collected in 2013 and the other in 2016, presented concurrently the mutations E138A, Discussion: However, the presence of three mutations (G140S, Q148H, and S147G) pose a higher risk of failing second-generation drugs.
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.
Introduction: Mutations that confer resistance to INSTIs (for example G140S, Q148H and N155H) have been structurally mapped in close proximity to the
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.
A Combination of M50I and V151I Polymorphic Mutations in HIV-1 Subtype B Integrase Results in Defects in Autoprocessing.
Result: After initial quality analysis, we excluded 27 sequences from four patients that contained integrase inhibitor (INI)-resistant mutations (Y143C/H/R; Q148H/K/R or N155H/S).
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).
Result: The most frequent surveillance drug resistance mutations (SDRMs) were K103NS (6.7%) to NNRTI; M41L (1.2%) and T215CDEF (2.1%) to NRTI; M46IL (1.7%) to PI; and E138AKT (0.2%), Q148HKR (0.1%), and S230R (0.1%) to INSTI (Fi
Three-year study of pre-existing drug resistance substitutions and efficacy of bictegravir/emtricitabine/tenofovir alafenamide in HIV-1 treatment-naive participants.
PMID: 33880558
2021
The Journal of antimicrobial chemotherapy
Abstract: One participant in the B/F/TAF group had pre-existing bictegravir and dolutegravir resistance substitutions (Q148H+G140S in integrase) at baseline and suppressed and maintained HIV-1 RNA <50 copies/mL through Week 144.
Structural basis of second-generation HIV integrase inhibitor action and viral resistance.
Abstract: Glutamine-148 histidine (Q148H) and glycine-140 serine (G140S) amino acid substitutions in integrase that result in clinical INSTI failure perturb optimal magnesium ion coordination in the enzyme active site.
Abstract: The expanded chemical scaffolds of second-generation compounds mediate interactions with the protein backbone that are critical for antagonizing viruses containing the Q148H and G140S mutations.
Introduction: An exception is Thr138: in HIV-1, E138T potentiates resistance of Q148H-containing viruses.
Introduction: As a start, we analyzed respective side chains in our SIVrcm PMID: 31518723
2020
Journal of global antimicrobial resistance
Abstract: Transmitted INSTI mutations (Q148H and G140S) responsible for high-level resistance to raltegravir and elvitegravir and intermediate resistance to dolutegravir and bictegravir were found, for the first time, in two individuals.
HIV-1 acquired drug resistance to integrase inhibitors in a cohort of antiretroviral therapy multi-experienced Mexican patients failing to raltegravir: a cross-sectional study.
Abstract: The Y143R/H/C substitutions were the most prevalent, followed by the N155H, and both Q148H/K and G140S/A in the same proportion.
Table: Discussion: On the other hand, we do not find a significant difference between the mean viral load of the subjects with DTG resistance compared to the subjects without DTG resistance (n = 22), nor with samples harbouring a G140S/A + Q148H/R/K combination (n = 3) as described in that study.
Discussion: This is important since the presence of the G140S mutation in combination with the Q148H mutation has been described to improve the viral fitness and increase the viral load in RAL-resistant subjects.
High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment.
PMID: 32105319
2020
The Journal of antimicrobial chemotherapy
Introduction: A recent report suggested that methionine at residue 74 was in closer proximity to T97 and F121 as compared with leucine at position 74 in a modelled subtype C integrase and, of note, L74F was found to contribute to high-level dolutegravir resistance when combined with major mutations G140S and Q148H.
HIV mutation literature information.
PMID: 
2021
International journal of environmental research and public health
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