Limits...
Drug resistance of a viral population and its individual intrahost variants during the first 48 hours of therapy.

Campo DS, Skums P, Dimitrova Z, Vaughan G, Forbi JC, Teo CG, Khudyakov Y, Lau DT - Clin. Pharmacol. Ther. (2014)

Bottom Line: By means of next-generation sequencing, HCV variants were obtained from sera collected at nine time points from 16 patients during the first 48 h after injection of IFN-α.IFN-resistance coefficients were calculated for individual variants using changes in their relative frequencies, and for the entire intrahost viral population using changes in viral titer.Population-wide resistance and presence of IFN-resistant variants were highly associated with pegylated IFN-α2a/ribavirin treatment outcome at week 12 (P = 3.78 × 10(-5) and 0.0114, respectively).

View Article: PubMed Central - PubMed

Affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

ABSTRACT
Using hepatitis C virus (HCV) and interferon (IFN) resistance as a proof of concept, we have devised a new method for calculating the effect of a drug on a viral population, as well as the resistance of the population's individual intrahost variants. By means of next-generation sequencing, HCV variants were obtained from sera collected at nine time points from 16 patients during the first 48 h after injection of IFN-α. IFN-resistance coefficients were calculated for individual variants using changes in their relative frequencies, and for the entire intrahost viral population using changes in viral titer. Population-wide resistance and presence of IFN-resistant variants were highly associated with pegylated IFN-α2a/ribavirin treatment outcome at week 12 (P = 3.78 × 10(-5) and 0.0114, respectively). This new method allows an accurate measurement of resistance based solely on changes in viral titer or the relative frequency of intrahost viral variants during a short observation time.

Show MeSH

Related in: MedlinePlus

Maximum likelihood trees of all the sequences from patients with resistant variants. Red: IFN-resistant variants; blue: IFN-sensitive variants.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4215939&req=5

Figure 5: Maximum likelihood trees of all the sequences from patients with resistant variants. Red: IFN-resistant variants; blue: IFN-sensitive variants.

Mentions: For all patients showing one or more IFN-resistant variants, we performed a phylogenetic analysis to ascertain the genetic relatedness between the sensitive and resistant variants. For each patient, resistant variants were always one or two nucleotides different from the sensitive variants in the same cluster. In addition, resistant sequences did not cluster together but were scattered mostly across other subpopulations (Figure 5).


Drug resistance of a viral population and its individual intrahost variants during the first 48 hours of therapy.

Campo DS, Skums P, Dimitrova Z, Vaughan G, Forbi JC, Teo CG, Khudyakov Y, Lau DT - Clin. Pharmacol. Ther. (2014)

Maximum likelihood trees of all the sequences from patients with resistant variants. Red: IFN-resistant variants; blue: IFN-sensitive variants.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4215939&req=5

Figure 5: Maximum likelihood trees of all the sequences from patients with resistant variants. Red: IFN-resistant variants; blue: IFN-sensitive variants.
Mentions: For all patients showing one or more IFN-resistant variants, we performed a phylogenetic analysis to ascertain the genetic relatedness between the sensitive and resistant variants. For each patient, resistant variants were always one or two nucleotides different from the sensitive variants in the same cluster. In addition, resistant sequences did not cluster together but were scattered mostly across other subpopulations (Figure 5).

Bottom Line: By means of next-generation sequencing, HCV variants were obtained from sera collected at nine time points from 16 patients during the first 48 h after injection of IFN-α.IFN-resistance coefficients were calculated for individual variants using changes in their relative frequencies, and for the entire intrahost viral population using changes in viral titer.Population-wide resistance and presence of IFN-resistant variants were highly associated with pegylated IFN-α2a/ribavirin treatment outcome at week 12 (P = 3.78 × 10(-5) and 0.0114, respectively).

View Article: PubMed Central - PubMed

Affiliation: Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

ABSTRACT
Using hepatitis C virus (HCV) and interferon (IFN) resistance as a proof of concept, we have devised a new method for calculating the effect of a drug on a viral population, as well as the resistance of the population's individual intrahost variants. By means of next-generation sequencing, HCV variants were obtained from sera collected at nine time points from 16 patients during the first 48 h after injection of IFN-α. IFN-resistance coefficients were calculated for individual variants using changes in their relative frequencies, and for the entire intrahost viral population using changes in viral titer. Population-wide resistance and presence of IFN-resistant variants were highly associated with pegylated IFN-α2a/ribavirin treatment outcome at week 12 (P = 3.78 × 10(-5) and 0.0114, respectively). This new method allows an accurate measurement of resistance based solely on changes in viral titer or the relative frequency of intrahost viral variants during a short observation time.

Show MeSH
Related in: MedlinePlus