Comparison of the population sequence- and model-predicted time-to-20% for HCV subtypes 1a (A) and 1b (B).

<p>The X-axis represents the inferred time-to-loss of detectable resistance by population sequencing and reflects the first visit wherein the patient did not have detectable resistant variants. The Y-axis relies on the algorithms defined here, wherein the rate of loss is modeled continuously for each patient. The majority of the data points fall to the right of the unity line, indicating that the model predicts more rapid times-to-20% than those estimated from population sequence data.</p

Kaplan-Meier curves for time-to-20% determined by population sequencing, model-predicted time-to-20%, and model-predicted time-to-1%.

<p>Results for patients with HCV subtypes 1a and 1b are shown in plots (A) and (B), respectively. Hash marks (∧) denote the censored observations indicating the time of the last visit for patients with virus that did not revert to <20% resistant. For clarity, these patients are explicitly denoted on the population sequence (“Pop. Seq.”) and model-predicted time-to-20% resistance curves only.</p

Population sequence-based and model-predicted median reversion times.

1<p>The 95% CI assumes a single value for each patient and does not incorporate uncertainity of individual predictions (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003772#pcbi.1003772.s005" target="_blank">Text S1</a>).</p

Hypothetical viral dynamics for a patient with viral breakthrough during telaprevir-based treatment.

<p>(A) Dynamics for the total viral load (Total, green), wild-type virus (WT, blue), and a telaprevir-resistant variant (Resistant, red) during and after treatment with telaprevir-based treatment. LOD is the limit of detection for the ‘total’ viral load quantification, and Seq. LOD is the limit of detection above which sequencing can be reliably performed (1000 IU/ml). The treatment phase is shown by the gray bar. (B) Corresponding percent resistance dynamics on a linear scale. Viral sequencing can be performed when the total viral load exceeds the sequencing assay LOD (solid red curve). The dashed lines at 20% and 5% show the limits of detection for population and clonal sequence data, respectively.</p

Model fit for patients with genotype 1b HCV.

<p>(A): Histogram of the log₁₀ objective function values (φ; see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003772#pcbi.1003772.e021" target="_blank">Equation 5</a>) for all patients with genotype 1b. Dashed lines and numbers show quantile information for the fits. Also shown are representative fits for patients whose objective function values fall in the (B) 70%, (C) 90%, (D) 95%, and (E) 100% quantiles. Solid lines represent the model predictions, solid points represent the clonal sequence data, and error bars show the range for population sequence results.</p