Method: Major INSTI resistance mutations (T66I, E92Q, F121Y, Y143CHR, S147G, Q148HKR, N155H) that confer substantial phenotypic resistance to at least one of the currently approved INSTI as well as minor INSTI resistance mutations (T66AK, L74 M, E92G, T97A, E138AK, G140AS, R263K) that increase INSTI resistance and/or viral
Prevalence of Integrase Strand Transfer Inhibitors (INSTI) Resistance Mutations in Taiwan.
Abstract: Of 30 sequences (47.6%) with INSTI-resistant mutations from raltegravir-experienced patients, 17 harboured Q148H/K/R, 8 N155H, and 6 Y143C/R.
Introduction: With one or two major mutations, such as Q148HKR +- G140SA, N155H +- E92Q or Y143CR +- T97A, a marked reduction of viral susceptibility to raltegravir and elvitegravir has been observed.
Method: The major INSTI mutations, which have been determined having a marked reduction of viral susceptibility to raltegravir and elvitegravir, include Y143C/H/R, PMID: 27532886
2016
PloS one
Abstract: The resistance of DTG is mainly shown in 13 integrase mutations (including T97T/A, E138E/D, V151V/I, N155H, Q148, Y143C/H/R, T66A and E92Q).
Abstract: The ten major integrase mutations (including N155H, Y143C/R, Q148H/R, Y143Y/H, L74L/M, E92Q, E138E/A, Y143C, Q148Q and
Transmitted drug resistance of HIV-1 strains among individuals attending voluntary counselling and testing in Taiwan.
PMID: 26404079
2016
The Journal of antimicrobial chemotherapy
Abstract: Among the seven major integrase mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R and N155H), only one strain harbouring the Q148R mutation was detected.
[Resistance profile and genetic barrier of dolutegravir].
PMID: 25858608
2015
Enfermedades infecciosas y microbiologia clinica
Abstract: Dolutegravir displays in vitro activity against mutant HIV-1 harboring any isolated resistance mutations selected during failures to raltegravir or elvitegravir (Y143C/H/, N155H, Q148H/K/R, E92G/Q, T66A/I/K, T97A, E138A/K, G140A/S).
Lack of integrase inhibitors associated resistance mutations among HIV-1C isolates.
PMID: 26626277
2015
Journal of translational medicine
Abstract: Neither major resistance-associated IN mutations (T66I/A/K, E92Q/G, T97A, Y143HCR, S147G, Q148H/R/K, and N155H) nor silent mutations known to change the genetic barrier were observed.
Conclusion: None of the previously reported major mutations (T66AIK, E92Q, Y143RCH, S147G, Q148HRK and N155H) associated with resistance to INIs were observed in HIV-1C Ethiopian isolates, indicating that
Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades.
PMID: 26311843
2015
The Journal of antimicrobial chemotherapy
Abstract: Among raltegravir recipients with viraemia (median 3523 HIV-1 RNA copies/mL), 113/255 (44.3%) had one or more major INI RAMs, most commonly N155H (45/255, 17.6%), Q148H/R/K + G140S/A (35/255, 13.7%) and Y143R/C/H (12/255, 4.7%).
Discussion: Consistent with available data, there was a strong preferential association of N155H with E92Q, Y143H/R/C with T97A, and G140S/A with Q148H/R/K.
Discussion: The three major recognized pathways of genotypic resistance to raltegravir (N155H, PMID: 25956162
2015
Antiviral research
Abstract: Our in vitro assays revealed that S119G/P/T alone exerted no effect on the susceptibility to INSTIs, whereas S119R enhanced the level of INSTI resistance induced by well-known INSTI resistance-associated mutations (Y143C, Q148H or N155H).
In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2.
Abstract: Integrase substitutions E92Q, Y143C, E92Q + Y143C, and Q148R conferred relatively low levels of resistance to dolutegravir in HIV-2ROD9 (2- to 6-fold), but Q148K, E92Q + N155H, T97A + N155H and
Abstract: In contrast, HIV-1NL4-3 mutants E92Q + N155H, G140S + Q148R, and T97A + Y143C showed 2-fold, 4-fold, and no increase in EC50, respectively, relative to the parental strain.
HIV-1 integrase genotyping is reliable and reproducible for routine clinical detection of integrase resistance mutations even in patients with low-level viraemia.
PMID: 25712318
2015
The Journal of antimicrobial chemotherapy
Abstract: At early genotyping (within 3 months of raltegravir treatment), Q148H/K/R and N155H mutations were detected regardless of the viraemia level, while Y143C/H/R was observed only in samples with viraemia >1000 copies/mL.
Abstract: At viraemia <=500 copies/mL, Q148H/K/R and N155H had the same prevalence (9.1%), while the Y143C/H/R was completely absent.