Discussion: A similar high genetic barrier to acquire mutations G140S or G140C has also been described in CRF02_AG compared with subtype B.
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 Q148H/R/K resistance pathway in subtype C.
Discussion: The G140S mutation has been shown to rescue the catalytic defect due to the Q148H mutation, enabling the recovery of viral fitness
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
Discussion: One participant in DAWNING had emergence of the integrase substitutions E138K, G140S, Q148H, and N155H.
Discussion: Similar to the participant from the present study, G140S and Q148H also emerged together with E138K and N155H in a participant who received dolutegravir monotherapy.
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 PMID: 34897227
2022
Journal of acquired immune deficiency syndromes (1999)
Result: This clinical isolate with Q148H+G140S was phenotypically susceptible to BIC (2.14-fold change, less than the cutoff of 2.5-fold), partially susceptible to DTG (4.45-fold change, greater than the cutoff of 4-fold), and resistant to EVG and RAL (PhenoSense Integrase assay, Monogram Biosciences).
Table: G140A/C/S
Discussion: As observed in the viremic individual in this study, BIC has broader phenotypic activity than other INSTIs, including DTG, against clinical isolates with Q148H + G140S combinations.
Discussion: For example, the combination of Q148H/K/R and G140A/C/S in the presence of additional substitutions c
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
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.
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.
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.
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.
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.
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.
HIV mutation literature information.
PMID: 
2022
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