Rapid Development of High-Level Resistance to Dolutegravir With Emergence of T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir.
PMID: 30568974
2018
Open forum infectious diseases
Conclusion: T97A was not detected by Sanger sequencing or by next-generation sequencing (NGS; Illumina), which has a sensitivity of c.
Conclusion: A repeat INSTI genotype noted T97A (Supplementary Tables 2 and 3).
Conclusion: NGS detected T97A in addition to the previously detected integrase mutations (Supplementary Table 2).
Conclusion: Retrospective NGS analysis of a plasma sample from November 2015 (while the individual was on RAL) did not reveal the T97A mutation.
Conclusion: Thus T97A emerged within 8 weeks of consistent DTG therapy.
Figure: Impact of T97A mutation on phenotypic sensitivity to dolutegravir in HIV-1 isolates with baseline partial sensitivity to dolutegravir.|m
Performance of Celera RUO integrase resistance assay across multiple HIV-1 subtypes.
PMID: 27993614
2017
Journal of virological methods
Abstract: Mutations associated with integrase resistance were observed in seven of the 106 (7%) clinical samples [one sample: Q148K; E138K; G140A; two samples: T97A and four samples: L74I].
Result: Differences in mutations were observed at three codons in integrase associated with integrase drug resistance (A128T, T97A and V151I).
Result: The following mutations were observed: Q148K; E138K; G140A in one sample; T97A in two samples; and T97A Mutation in 2 Treatment-Experienced Individuals With Baseline Partial Sensitivity to Dolutegravir.
Abstract: A comparison between pre-existing and emergent T97A patient populations (i.e., in the absence of primary INSTI RAMs) showed no significant differences in EVG or RAL susceptibility in vitro.
Abstract: During INSTI-based therapy, few patients experienced virologic failure with emergent INSTI RAMs (3%; 122 of 3881 patients), among whom T97A emerged infrequently in the presence (n = 6) or absence (n = 8) of primary INSTI RAMs.
Abstract: Furthermore, among all T97A-containing viruses tested, only 38-44% exhibited reduced susceptibility to EVG and/or RAL (all of low magnitude; <11-fold), while all maintained susceptibility to dolutegravir.
Abstract: However, detection of T97A does no
Week 48 resistance analysis of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF versus Atazanavir + Ritonavir + Emtricitabine/Tenofovir DF in HIV-1 infected women (WAVES study GS-US-236-0128).
Abstract: Pre-existing mutations did not lead to virologic failure; most with the polymorphic primary IN substitution T97A (92%), or with substitutions in
Method: Primary INSTI-R substitutions assessed were T66A/I/K, E92G/Q, T97A, Y143C/H/R, S147G, Q148H/K/R, and N155H/S in IN.
Discussion: Ten participants treated with EVG/COBI/FTC/TDF had the polymorphic primary IN resistance substitution T97A by deep sequencing, and all of these participants had <50 copies/mL HIV-1 RNA at Week 48.
Antiviral Activity of Bictegravir and Cabotegravir against Integrase Inhibitor-Resistant SIVmac239 and HIV-1.
PMID: 28923862
2017
Antimicrobial agents and chemotherapy
Abstract: In single cycle SIV infections, none of the E92Q, T97A, Y143R, or N155H substitutions had a significant effect on susceptibility to BIC (<=4-fold increase in EC50), whereas G118R and R263K conferred ~14-fold and ~6-fold increases in EC50, respectively.
Molecular evolution of HIV-1 integrase during the 20 years prior to the first approval of integrase inhibitors.
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
Deep analysis of HIV-1 natural variability across HIV-1 variants at residues associated with integrase inhibitor (INI) resistance in INI-naive individuals.
PMID: 26546669
2016
The Journal of antimicrobial chemotherapy
Abstract: Three secondary INI-R changes appeared with variable frequency in INI-naive individuals carrying specific HIV-1 variants: L74M in CRF43_02G (33.3%); T97A in group P (50%), J (33.3%), CRF18_cpx (20%) and F2 (11.5%); and G163RK in CRF44_BF (100%), CRF46_BF (66.7%), CRF17_BF (28.6%), F1 (21.7%), CRF12_BF (16.7%) and CRF29_BF (12.5%).
Efficacy and safety of antiretroviral regimens including raltegravir to treat HIV-infected patients with hemophilia.
Discussion: Although for the remaining patient we could not demonstrate the failing mutation with Sanger sequencing, using a more sensitive test, resulted in the correct identification of the failing mutations [N155H (9.7 %) and T97A (12.42 %)] suggesting that, given the superiority of massive parallel sequencing, this should be the tool recommended for testing proviral DNA in virologically suppressed patients, although at present it is an expensive tool that may not be feasible in some laboratories.
Therapy-Emergent Drug Resistance to Integrase Strand Transfer Inhibitors in HIV-1 Patients: A Subgroup Meta-Analysis of Clinical Trials.
HIV mutation literature information.
PMID: 
2018
Open forum infectious diseases
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