RESUMEN

It is unclear if HIV-1 variants lose the ability to prime naïve CD8(+) cytotoxic T lymphocytes (CTL) during progressive, untreated infection. We conducted a comprehensive longitudinal analysis of viral evolution and its impact on primary and memory CD8(+) T cell responses pre-seroconversion (SC), post-SC, and during combination antiretroviral therapy (cART). Memory T cell responses targeting autologous virus variants reached a nadir by 8 years post-SC with development of AIDS, followed by a transient enhancement of anti-HIV-1 CTL responses upon initiation of cART. We show broad and high magnitude primary T cell responses to late variants in pre-SC T cells, comparable to primary anti-HIV-1 responses induced in T cells from uninfected persons. Despite evolutionary changes, CD8(+) T cells could still be primed to HIV-1 variants. Hence, vaccination against late, mutated epitopes could be successful in enhancing primary reactivity of T cells for control of the residual reservoir of HIV-1 during cART.

Asunto(s)

Epítopos de Linfocito T/inmunología , Evolución Molecular , Infecciones por VIH/inmunología , VIH-1/genética , Linfocitos T/inmunología , Adulto , Fármacos Anti-VIH/uso terapéutico , Linfocitos T CD8-positivos/inmunología , Estudios de Cohortes , Epítopos de Linfocito T/genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Infecciones por VIH/virología , VIH-1/inmunología , VIH-1/aislamiento & purificación , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/inmunología , Humanos , Masculino , Linfocitos T/virología , Proteínas Virales/genética , Proteínas Virales/inmunología