Clonal evolution of CD8+ T-cell expansions in HIV-infected patients on long-term HAART.

HIV-1 continually replicates in spite of long-term highly active anti-retroviral therapy (HAART) and therefore, it is conceivable that the low level, persistent viral activity could continue to stimulate the hosts immune system despite remaining below the detection limit of the current assays. In this study, we performed a longitudinal analysis of the CD8+ T-cell receptor Vbeta repertoire in HAART-treated and untreated HIV patients. HAART-mediated control of viremia, for up to 18 months, did not prevent similar perturbations within the CD8+ Vbeta repertoire in both study groups as defined by CDR3 spectratyping. Oligoclonal Vbeta expansions, with new dominant CDR3 lengths, were observed throughout the study period. Our findings are compatible with antigen-driven CD8+ immune responses to bursts of replication from a continuously changing viral reservoir, regardless of HAART-mediated suppression of HIV-1 viremia.