Constructing lower-bounds for CTL escape rates in early SIV infection

Abstract

Intrahost human and simian immunodeficiency virus (HIV and SIV) evolution is marked by repeated viral escape from cytotoxic T-lymphocyte (CTL) response. Typically, the first such CTL escape starts around the time of peak viral load and completes within one or two weeks. Many authors have developed methods to quantify CTL escape rates, but existing methods depend on sampling at two or more timepoints. Since many datasets capture the dynamics of the first CTL escape at a single timepoint, we develop inference methods applicable to single timepoint datasets. To account for model uncertainty, we construct estimators which serve as lower bounds for the escape rate. These lower-bound estimators allow for statistically meaningful comparison of escape rates across different times and different compartments. We apply our methods to two SIV datasets, showing that escape rates are relatively high during the initial days of the first CTL escape and drop to lower levels as the escape proceeds.