Figure 3. Transmitted adaptation establishes clinical prognosis and largely explains which HLA alleles are protective.

(a, b) Pre-adaptation of donor virus to the recipient HLA alleles among Zambian Transmission Pairs predicts CD4 decline (a) and early setpoint VL (b). (a) For visualization, individuals are stratified into above (red) and below (blue) mean transmitted adaptation; here, adaptation is scaled to define a unit change as the difference of transmitted adaptation means between the two strata. Hazard ratio (HR) and two-tailed P-value from Cox proportional hazard, computed from continuous value. Data for all individuals with longitudinal CD4 counts are shown. (c) Adaptation of founder virus from infected participants of the Step vaccine trial. Data from all individuals in both vaccine and placebo arms with at least two VL measurements prior to initiation of therapy). R_s, P-value, Spearman rank correlation. Best fit and 95% CI lines from unadjusted model. See Supplementary Table 2 for mixed model with additional covariates.