Abstract
Novel integrase inhibitors are in advanced clinical development, and cross-resistance data are needed to consider the possibility to plan a sequential usage within this class of antiretroviral drugs. Ex vivo phenotypic assays were conducted on 11 wild-type and 27 fully replicating recombinant viruses obtained from 11 patients failing previous raltegravir-containing regimens. Dolutegravir maintained its activity in vitro on viruses with mutations in position 143 and 155. However, viruses with mutation Q148R associated with secondary mutations and the combination Q148H+G140S were instead associated with a reduced level of susceptibility to dolutegravir in vitro.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Substitution / genetics
-
Anti-HIV Agents / pharmacology*
-
Drug Resistance, Viral / genetics*
-
HIV Infections / drug therapy*
-
HIV Infections / virology
-
HIV Integrase / genetics
-
HIV Integrase Inhibitors / pharmacology*
-
HIV-1 / drug effects*
-
HIV-1 / enzymology
-
HIV-1 / genetics*
-
Heterocyclic Compounds, 3-Ring / pharmacology*
-
Humans
-
Inhibitory Concentration 50
-
Microbial Sensitivity Tests
-
Mutation
-
Oxazines
-
Phenotype
-
Piperazines
-
Pyridones
-
Pyrrolidinones / pharmacology
-
Raltegravir Potassium
Substances
-
Anti-HIV Agents
-
HIV Integrase Inhibitors
-
Heterocyclic Compounds, 3-Ring
-
Oxazines
-
Piperazines
-
Pyridones
-
Pyrrolidinones
-
Raltegravir Potassium
-
dolutegravir
-
HIV Integrase