HIV-specific CD4+ T cells and viremia: whoʹs in control?

It has been proposed that HIV-specific CD4+ T cells with a central memory phenotype might be involved in controlling HIV replication. Based on recent data (lack of protective effects of HIV-specific CD4+ T-cell responses in acutely infected patients undergoing treatment interruptions; loss of initially strong T-helper cell responses in progressors to AIDS; and lack of prognostic value of HIV-specific CD4+ T cells in a prospective study) we argue that the level of persistent viremia determines the fate of HIV-specific CD4+ T cells. We postulate that, rather than the absence of HIV-specific T cells, it is the viral and immune activation set points that are major determinants of progression to AIDS. This influences ideas about the type of cellular immunity a protective HIV vaccine should induce.