Abstract: Analysis of the genetic barrier showed that the Q148H/K/R dolutegravir resistance pathway was less selected in subtype C.
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,
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.
Abstract: Major INSTI-mutations E138K, Y143R, S147G, Q148R, N155H, and E157Q were found in raltegrav
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 Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine.
PMID: 34978890
2022
Antimicrobial agents and chemotherapy
Result: Emergence of resistance mutations in breakthrough viruses was rare, with only 1 replicate of NL4-3 L74I containing a Q148R mutation with 5 nM cabotegravir.
Result: However, when Q148R was introduced into either clone, EC50 values against cabotegravir were increased, with fold changes of 4.4 and 4.1 for NL4-3 and ConA6-containing viruses, respectively.
Result: In addition to the L74I polymorphism, each participant who met CVF criteria had treatment-emergent INSTI resistance mutations of either G140R (n = 1) or Q148R (n = 2).
Result: No Q148R mutations were observed when additional replicates were repeated in 3 independent experiments at 5 nM cabotegravir for >=100 days, indicating that the occurrence of
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)
Abstract: Most of the participants (n = 19) were virologically suppressed at baseline and had one primary INSTI-R substitution, E92G, Y143C/H, S147G, Q148H
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: Q148R
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
Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations.
Discussion: These mutations are located in close proximity to the Integrase's active site and each mutation significantly reduces viral fitness by 92-fold for Q148R, 30-fold for N155H.
Discussion: Two principal mutation pathways identified from our study that reduces susceptibility to RAL are Q148H/K/R and N155H.
HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana.
Result: Amongst the individuals previously exposed to RAL ART (seven out of eleven), DRMs selected whilst failing their current DTG based regimens were E138K, G140A, Q148R; and N155H Figure 3.
Discussion: Comparable with others, amongst individuals with prior exposure to RAL, the most common mutations selected were N155H (n = 4), Q148R (n = 4), S147G (n = 4) and E138K (n = 3) as others have similarly found.
Discussion: In our study, E138K (n = 5), S147G (n = 4), Q148R (n = 4) and N155H (n = 4) where the most frequent INSTI D
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: 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
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
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