Abstract
Whether or not HIV-1 continues to infect cells in individuals treated with effective antiretroviral therapy (ART) remains controversial. Here, we determined whether the redistribution of the HIV-1 proviral burden with respect to antigen specificity of CD4(+) cells would provide evidence for ongoing infection cycles in vivo. HIV-1 preferentially infects antigen-stimulated CD4(+) T cells. In the setting of prolonged effective ART, we postulated that if infection cycles were occurring, influenza-specific CD4(+) T cells, activated by influenza vaccination, would preferentially accumulate proviral burden. Peripheral blood mononuclear cells (PBMCs) were collected from HIV-1-infected subjects who had been treated with effective ART for >5 years, before and after influenza vaccination. CD4(+) T cells were sorted by antigen specificity and HIV-1 proviral burdens were determined. Levels of HIV-1 production upon in vitro antigenic stimulation were also measured. At baseline, influenza-specific CD4(+) T cells carried higher HIV-1 proviral loads than HIV-1-p55-specific CD4(+) T cells. Upon influenza vaccination we observed trends toward elevated levels of HIV-1 proviral DNA in influenza and HIV-1-p55-specific, but not tetanus toxoid or cytomegalovirus (CMV)-specific CD4(+) T cells. Higher levels of HIV-1 virions were produced upon influenza stimulation in postvaccination as compared to baseline samples. While the trends toward increased proviral burdens in influenza-specific cells failed to reach statistical significance, our observation of disproportionately high levels of provirus in influenza-specific cells at baseline indicates that this may represent a real increase that is cumulative over multiple annual vaccinations. This has implications for the eradication of HIV-1 by adding to the evidence that the resting CD4(+) T cell viral reservoir is continually replenished in ART-treated subjects.