Collinearity of protease mutations in HIV-1 samples with high-level protease inhibitor class resistance.
J Antimicrob Chemother
; 68(2): 414-8, 2013 Feb.
Article
en En
| MEDLINE
| ID: mdl-23085775
ABSTRACT
OBJECTIVES:
To determine whether pan-protease inhibitor (PI)-resistant virus populations are composed predominantly of viruses with resistance to all PIs or of diverse virus populations with resistance to different subsets of PIs.METHODS:
We performed deep sequencing of plasma virus samples from nine patients with high-level genotypic and/or phenotypic resistance to all licensed PIs. The nine virus samples had a median of 12 PI resistance mutations by direct PCR Sanger sequencing.RESULTS:
For each of the nine virus samples, deep sequencing showed that each of the individual viruses within a sample contained nearly all of the mutations detected by Sanger sequencing. Indeed, a median of 94.9% of deep sequence reads had each of the PI resistance mutations present as a single chromatographic peak in the Sanger sequence. A median of 5.0% of reads had all but one of the Sanger mutations that were not part of an electrophoretic mixture.CONCLUSIONS:
The collinearity of PI resistance mutations in the nine virus samples demonstrated that pan-PI-resistant viruses are able to replicate in vivo despite their highly mutated protease enzymes. We hypothesize that the marked collinearity of PI resistance mutations in pan-PI-resistant virus populations results from the unique requirements for multi-PI resistance and the extensive cross-resistance conferred by many of the accessory PI resistance mutations.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteasa del VIH
/
VIH-1
/
Inhibidores de la Proteasa del VIH
/
Mutación Missense
/
Farmacorresistencia Viral
Límite:
Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos