literature

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%).

Method: Major RAMs comprised T66A/I/K, E92Q/G/V, F121Y, G140S/A/C, Y143H/R/C/K, S147G, Q148H/R/K and N155H/S/T.

Result: Conversely, mutations that were mutually exclusive comprised

PMID: 26198244 2015 Viruses

Table: Y143H

[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).

In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2.

PMID: 25808007 2015 Retrovirology

Result: In the VIKING-3 trial, dolutegravir response rates (<50 HIV-1 RNA copies/ml at week 24) declined from 79% (n = 100/126) for patients without Q148 mutations at baseline (including those with N155H, Y143C/H/R, T66A, E92Q, or historical evidence of INSTI resistance), to 58% (21/36) for patients with Q148 plus one additional secondary mutation, to 24% (5/21) for those with Q148 plus two or more secondary mutations.

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.

Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients.

PMID: 25558077 2015 The Journal of antimicrobial chemotherapy

Abstract: The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%).

Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013.

PMID: 24831260 2015 Antiviral therapy

4Method: Sequences were assembled with Sequencher (version 4.9; Gene Codes Corp, Ann Arbor, Ml) and submitted to the Stanford University HIV Drug Resistance Database (version 6.3.0; http://hivdb.stanford.edu on August 21, 2013) to identify ""major"" INSTI mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Abstract: Consensus sequencing identified no subjects with major INSTI mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R, N155H).

2014 Update of the drug resistance mutations in HIV-1.

PMID: 25101529 2014 Topics in antiviral medicine

Discussion: Mutations described in the N155H pathway include this major mutation plus either L74M, E92Q, T97A, E92Q plus T97A, Y143H, G163K/R, V151I, or D232N.

Discussion: Raltegravir failure is associated with integrase mutations in at least 3 distinct, but not exclusive, genetic pathways defined by 2 or more mutations including (1) a signature (major) mutation at Q148H/K/R, N155H, or Y143R/H/C; and (2) 1 or more additional minor mutations.

Discussion: The

PMID: 24359837 2014 International journal of antimicrobial agents

Abstract: At failure, major RAL resistance mutations included Q148H/R/K (21/47; 45%), N155H (14/47; 30%), Y143R/H/C (3/47; 6%) and E92Q (1/47; 2%).

Resistance to HIV integrase strand transfer inhibitors among clinical specimens in the United States, 2009-2012.

PMID: 24145878 2014 Clinical infectious diseases

Abstract: Major integrase mutations included T66AIK, E92QV, F121Y, Y143CHR, S147G, Q148HKR, and N155H; multiple accessory mutations were also assessed.