Constructing Lower-Bounds for CTL Escape Rates in Early HIV and SIV Infection

Abstract

Intrahost simian immunodeficiency virus (SIV) evolution is marked by repeated viral escape from cytotoxic T-lymphocyte (CTLs) response. Typically, the first such CTL escape occurs in a matter of days, starting around the time of peak viral load. Many authors have developed methods to quantify the strength of CTL response by measuring the rate at which CTL escape occurs, but such methods usually depend on sampling at two or more timepoints, while many datasets capture the dynamics of the first CTL escape at only a single timepoint. Here, we develop inference methods for CTL escape rates applicable to single timepoint datasets. Through a model of early infection dynamics, we construct confidence intervals for escape rates, but since early infection dynamics are not completely understood, we also develop a one-sided confidence interval serving as a lower bound for escape rates over a collection of early infection models. We apply our methods to two SIV datasets, using our lower bounds and existing methods to show that escape rates are relatively high during the initial days of the first CTL escape and then drop to lower levels as the escape proceeds. We also compare escape in the lymph nodes and the rectal mucosa, showing that escape in the lymph nodes is initially faster, but as the first escape proceeds, the rate of escape in the lymph nodes drops below the rate seen in the rectal mucosa.