Variants with different mutation patterns persist in the quasispecies of enfuvirtide-resistant HIV-1 population during and after treatment in vivo.
J Acquir Immune Defic Syndr
; 46(2): 134-44, 2007 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-17621239
ABSTRACT
BACKGROUND:
Genotypic and phenotypic resistance in 11 HIV-1-infected patients receiving enfuvirtide (ENF), as part of a salvage regimen, has been evaluated.METHODS:
Resistance mutations were detected by sequencing the gp41 ectodomain from plasma samples. During treatment, longitudinal samples from 1 patient were sequenced after limiting dilution of complementary DNA to isolate single genomes. Phenotypic resistance was evaluated with a new recombinant virus assay (PHENOSCRIPT; VIRalliance, Paris, France), allowing the determination of coreceptor use.RESULTS:
All patients experienced ENF failure. One to 4 mutations in the 36-to-45 gp41 region appeared during ENF therapy in all patients and disappeared after ENF removal. Mixtures of wild type and mutants unexpectedly persisted under ENF treatment, however, despite continued replication, leading to discordant results between genotypic and phenotypic data. Sequencing of isolated genomes from 1 patient confirmed that a wild-type first heptad repeat region (HR1) region was still present at the end of therapy. Several mutated variants coexisted at different time points, despite a tendency toward quasispecies reduction with time.CONCLUSION:
Individual variability of the mutation pattern and persistence of strains without mutation in the region mainly targeted by ENF resistance probably reflect the fact that resistance to ENF may rely on regions of gp41 or gp120 other than residues 36 to 45.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Proteína gp41 do Envelope de HIV
/
Infecções por HIV
/
HIV-1
Tipo de estudo:
Observational_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article