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<
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.
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).
Table: Q148H/K/R
Table: Q148K
Discussion: For example, the combination of Q148H/K/R and G140A/C/S in the presence of additional substitutions can cause high-level resistance to BIC (>10-fold change in phenotype compared with wild type) but as was seen with the naive case presented
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
Table: Q148H/K/R
Cellular Immune Response Induced by DNA Immunization of Mice with Drug Resistant Integrases of HIV-1 Clade A Offers Partial Protection against Growth and Metastatic Activity of Integrase-Expressing Adenocarcinoma Cells.
Result: Using this gene as a platform, we further designed IN variants harboring two sets of mutations conferring resistance to RAL, one with primary resistance mutation N155H and secondary mutations L74M, E92Q, V151I, G163R (IN_a_r1); and the other, with primary resistance mutation Q148K and secondary mutations E138K and G140S (IN_a_r2).
Discussion: We synthesized an expression optimized gene encoding consensus integrase (IN) of HIV-1 clade A, and using it as a platform, two drug resistant variants with alternative patterns of resistance to raltegravir combining primary and early occurring secondary/adaptive
Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study.
Method: INSTI mutations, which are not included on this list, were defined as those on the Stanford HIVdb surveillance DRM list, namely T66AIK, E92Q, F121Y, G140ACS, Y143CHR, S147G, Q148HKR and N155HS.
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: 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 integrase mutations in our analyzed patient samples were the Q148HKR (31%), G140S (28%), and, although at lower frequencies, we were able to identify the N155H, S147G, Y143R
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.
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 T66
Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations.
Discussion: Two principal mutation pathways identified from our study that reduces susceptibility to RAL are Q148H/K/R and N155H.
Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study.
PMID: 34397746
2021
Journal of acquired immune deficiency syndromes (1999)
Result: Two participants were found to have baseline INSTI resistance based on historical genotype data and were excluded from the primary analysis because of this protocol violation; 1 participant each with Y143C and Q148K mutations, both were randomized to B/F/TAF and had HIV-1 RNA <50 copies/mL at week 24.
HIV mutation literature information.
PMID: 
2022
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