The Impact Of Viral Evolution And Frequency Of Variant Epitopes On Primary And Memory Hiv-1-Specific Cd8+ T Cell Responses

It is not clear if HIV-1 variants lose the ability to prime naive CD8+ cytotoxic T lymphocytes (CTL) during progressive, untreated infection. Answering this question is important for developing immunotherapeutic approaches for enhanced control of residual HIV-1 infection in persons on combination antiretroviral therapy (cART). We therefore 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 cART. We report the emergence of variant sequences in Gag, Env, and Nef at early (0-3 yr) and late (3.3-7.8 yr) times following SC, and after ART (>8 yr). Memory T cell responses targeting autologous virus variants reached a nadir by 8 yr post-SC along with the development of AIDS. This was followed by a transient enhancement of anti-HIV-1 CTL responses upon initiation of cART. The frequency of epitope variants was clearly associated with the breadth but not the magnitude of memory T cell responses. Ou...