Abstract: Of note, the remaining patients on RAL regimens for 14 +- 3 months harbored no or only minor integrase mutations/polymorphisms (T66I, T97A, H114P, S119P, A124S, G163R, I203M, R263K).
G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not.
PMID: 21576445
2011
Antimicrobial agents and chemotherapy
Abstract:
Abstract: Assays without RAL suggested that the T97A mutation could rescue the catalytic activity which was impaired by the presence of the Y143C/R mutation.
Abstract: FCs of 18 and 100 were observed with the strand transfer assay for IN Y143C/T97A and Y143R/T97A mutations, with IC(50) of 0.625 muM and 2.5 muM, respectively.
Abstract: In the strand transfer assay, the IN Y143C or R mutation combined with the secondary mutation T97A severely impaired susceptibility to RAL compared to results with the IN Y143C or R mutation alone.
Switching between raltegravir resistance pathways analyzed by deep sequencing.
Result: We also detected T97A, an accessory mutation for Y143R, and L74M and E92Q, accessory mutations for N155H, from the forward read sets (data not shown).
G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not.
Method: Single (E92Q, T97A, G140S, Q148R, Y143C, N155H) and double (G140S/Q148R, Y143C/N155H, E92Q/Y143C and T97A/Y143C) mutations were introduced into the HIV-2 wild-type N1 sequence by mutagenesis using the QuickChange II site-directed mutagenesis kit (Agilent Technologies, Santa Clara, USA) according to the manufacturer instructions.
Result: The introduction of T97A into the Y143C background did not lead to detectable
G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not.
Discussion: For the N155H mutation, the level of resistance conferred by single-site directed mutagenesis was very similar to that of the enzyme amplified from the E92A/T97A/N155H clinical isolate, suggesting that the E92A and T97A secondary mutations provided no additional resistance.
Discussion: Our clonal analysis based on seven clinical isolates identified three different patterns, E92A/T97A/N155H, G140S/Q148R and E92Q/143C, confirming the probable existence of these three pathways.
Discussion: This hypothesis is consistent with the absence of resistance observed fo
Long-lasting persistence of integrase resistance mutations in HIV-2-infected patients after raltegravir withdrawal.
Abstract: At M18 after RAL stop, integrase genotypic pattern evolved to T97A/Y143G.
Abstract: In patient 3, RAL-resistant virus with T97A/N155H mutations were still present 1 month after stopping RAL, and were no longer detected at M14.
Abstract: RESULTS: At the time of RAL withdrawal, virus exhibited different integrase resistance pathways: G140S/Q148R, E92Q/N155H, T97A/N155H an
Abstract: Regarding patient 4, the mutant T97A/Y143C was still detected at M1 and M3 following RAL withdrawal.
Phenotypic susceptibility of HIV-2 to raltegravir: integrase mutations Q148R and N155H confer raltegravir resistance.
Discussion: Studies of HIV-1 patients have identified three principal mutational patterns that emerge in response to raltegravir treatment: Q148H/K/R with or without G140S/A, N155H with or without E92Q and Y143C/R with or without T97A.
Natural polymorphisms of integrase among HIV type 1-infected South African patients.
PMID: 20377427
2010
AIDS research and human retroviruses
Abstract: However, one sample had the T97A mutation, three samples had the E157Q and V165I mutations, and the majority of samples contained the polymorphic mutation V72I.
G140S/Q148R and N155H mutations render HIV-2 Integrase resistant to raltegravir whereas Y143C does not.
Discussion: Moreover, our cloning analysis showed that some clones could carry T97A in the absence of Y143C/R and other major mutations, suggesting that T97A could be sufficient to code resistance to RAL.
Discussion: Selection of the Y143R/C mutation was accompanied in all three patients by the T97A mutation.
Discussion: The Y143C/H/R mutation was associated with T97A in 3 patients, with L74M in 2 patients and with G163R and S230R in one patient each.
Discussion: When the viruses of these three patients replicated on therapy, selection of the mutations L74M, PMID: 20436677
2010
PloS one
Result: Clonal analysis also showed that the T97A and G163R mutations could be present in association with Y143R but could also be selected in the absence of Y143R (in patients 2 and 3).
Table: T97A/T
Discussion: Further experiments should focus on the role of T97A by introducing this mutation alone into the integrase gene.
Discussion: This co-selection of secondary mutations, particularly T97A, along with the mutations at position 143 are in agreement with other studies.
HIV mutation literature information.
PMID: 
2011
Journal of medical virology
Browser Board
Co-occurred Entities
Filtrator
ViMRT