Abstract: Analysis of the genetic barrier showed that the Q148H/K/R dolutegravir resistance pathway was less selected in subtype C.
Discussion: It does not decrease INSTI susceptibility alone, but it can contribute to a high-level resistance when occurring with major INSTI-resistance mutations, mainly the Q148H/K/R mutation.
Discussion: Overall, our analysis of the codon distribution of the selected amino acid position of HIV-1 subtype C and subtype B revealed a similar genetic barrier for the development of DTG resistance between subtype C and B, except at codon position 140, where subtype C had a higher genetic barrier to develop the G140C and G140S mutations compared to subtype B, highlighting a higher genetic barrier for the PMID: 35240975
2022
Current HIV research
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.
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.
Impact of combinations of clinically observed HIV integrase mutations on phenotypic resistance to integrase strand transfer inhibitors (INSTIs): a molecular study.
PMID: 35061879
2022
The Journal of antimicrobial chemotherapy
Abstract: Addition of E138K to G140S/Q148H conferred 35.5, 11.6 and 208-fold reduced susceptibility to dolutegravir, bictegravir, and cabotegravir, while addition of T97A to G140S/Q148H conferred 318, 121 and >1000-fold reduced susceptibility to these drugs.
Abstract: BACKGROUND: Routine HIV drug resistance genotyping identified an integrase sequence harbouring T97A, E138K, G140S and Q148H, with high predicted resistance to all integrase strand transfer inhibitors (INSTIs).
Abstract: Notably, bictegravir EC50 was significantly
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)
Result: Of the 8 amino acid positions listed with primary INSTI-R substitutions, 6 were detected in these participants: E92G (n = 3; 15%), Y143C/H (n = 6; 30%), S147G (n = 2; 10%), Q148H/K/R (n = 6; 30%), N155S (n = 1; 5%), and R263K (n = 2; 10%) (Table 2).
Result: The treatment-naive participant had K103N and K70R in RT and Q148H and G140S in IN genes.
Result: The treatment-naive participant with preexisting Q148H and G140S had a viral l
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
Result: The sixth participant had treatment-emergent Q148H and N155H in combination with other integrase substitutions.
Table: Q148H/K/R
Discussion: One participant in DAWNING had emergence of the integrase substitutions E138K, G140S, Q148H, and N155H.
Discussion: Treatment with raltegravir and elvitegravir frequently selects for G140S and Q148H in combination, although emergence of major INSTI resistance-associated substitutions together, such as Q148H and N155H, occu
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
Result: Interestingly, two samples, one collected in 2013 and the other in 2016, presented concurrently the mutations E138A, G140S, and Q148H, which confer high-level resistance to all INSTIs, including BIC (Table 2).
Result: Nevertheless, when combined with Q148QKH, they can provide high-level resistance to RAL or EVG and reduce DTG or BIC efficacy.
Result: Previous studies have demonstrated that HIV-1 patient samples harboring these mutations (E138EA, G140S, and Q148HKR) show high-level resistance to INSTIs, and these combinations were identified in 1.52% of our sequences.
Result: The most frequent PMID: 33807382
2021
Viruses
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.
Discussion: It was recently shown that it is only upon the development of the T97A mutation that variants harboring Q148H and G140S Integrase mutations started to have increased VLs.
Long Dissociation of Bictegravir from HIV-1 Integrase-DNA Complexes.
PMID: 33649107
2021
Antimicrobial agents and chemotherapy
Abstract: BIC also had a longer t1/2 and maintained longer antiviral activity after drug washout than DTG with the clinically relevant resistance IN mutant G140S+Q
Table: Q148H
Figure: The INSTIs were docked to a homology model of WT and G140S+Q148H mutant HIV-1 IN based on cryo-EM structures (SIVrcm IN) using Prime in Schrodinger Suite 2019-2 (Schrodinger, LLC, New York, NY) and a knowledge-based approach.
Figure: Viral replication of WT (A) and G140S+Q148H (B) variants after treatment with DTG, BIC, EVG, and RAL following drug washout (Delta) starting at washout day 0 (3 days postinfection).
Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa.
Discussion: Previous studies on HIV-1C have shown major INI mutations at baseline in less than 5% of patients from Ethiopia (T66I, E138K, Q148R, and Q148H) and South Africa (Q148H, T66S, E92G, S147G, T66A, Y143YF and Y143H).
HIV mutation literature information.
PMID: 
2022
Viruses
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