literature

Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile.

PMID: 27645238 2016 Antimicrobial agents and chemotherapy

Figure: Primary INSTI resistance mutations are T66I/A/K, E92Q/G, T97A, Y143C/H/R, S147G, Q148H/K/R, and N155H, and other INSTI resistance mutations are H51Y, L68I/V, V72A/N/T, L74M, Q95K/R, F121C/Y, A128T, E138A/K, G140A/C/S, P145S,

PMID: 27779200 2016 Scientific reports

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, Q148H/K/R, and N155H.

Result: Among the INSTI-experienced patients, only one (1.6%) had Q148H/R/K along with two or three of

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).

Antiviral characteristics of GSK1265744, an HIV integrase inhibitor dosed orally or by long-acting injection.

PMID: 25367908 2015 Antimicrobial agents and chemotherapy

Abstract: GSK1265744 demonstrated activity against SDM clones containing the raltegravir (RAL)-resistant Y143R, Q148K, N155H, and G140S/Q148H signature variants (FC less than 6.1), while these mutants had a high FC in the EC50 for RAL (11 to >130).

High frequency of dolutegravir resistance in patients failing a raltegravir-containing salvage regimen.

PMID: 25386009 2015 The Journal of antimicrobial chemotherapy

Abstract: RESULTS: Among the 92 patients analysed, 32 (35%) showed resistance to dolutegravir, in most cases associated with the combination of Q148H/R/K with G140S/A mutations.

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%).

Effects of raltegravir or elvitegravir resistance signature mutations on the barrier to dolutegravir resistance in vitro.

PMID: 25691633 2015 Antimicrobial agents and chemotherapy

Abstract: E138K and G140S, as secondary substitutions to Q148H, Q148K, or Q148R, were associated with partial recovery in viral infectivity and/or INSTI resistance.

Abstract: In the Q148H, Q148K, or Q148R mutants, G140S/Q148H, E138K/Q148K, E138K/Q148R, and G140S/Q148R secondary mutations were identified with each INSTI and showed high resistance to RAL o

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.

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

PMID: 25808007 2015 Retrovirology

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 G140S + Q148R resulted in moderate resistance (10- to 46-fold), and the combination of T97A + Y143C in HIV-2ROD9 conferred high-level resistance (>5000-fold).

Result: In contrast, mutants Table: Q148K

[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).