Mechanisms of HIV non-progression; robust and sustained CD4+ T-cell proliferative responses to p24 antigen correlate with control of viraemia and lack of disease progression after long-term transfusion-acquired HIV-1 infection

Dyer, Wayne B; Zaunders, John J; Yuan, Fang Fang; Wang, Bin; Learmont, Jennifer C; Geczy, Andrew F; Saksena, Nitin K; McPhee, Dale A; Gorry, Paul R; Sullivan, John S

Our studies have demonstrated that host and viral genetic factors can contribute to delayed disease progression, but the single immunological factor that functionally defined non-progression was Gag-specific CD4 T cell proliferation. The maintenance of this p24-specific response does not require detectable viral replication for antigenic stimulation [41] . Detectable p24-specific T cell proliferation defines the immunocompetent recall response to viral antigen, and when spikes of viral replication were detected in these individuals, these cells likely provided T cell help for maintaining functional antiviral effector responses by other CD4 and CD8 T cells, including noncytolytic antiviral mechanisms [41] , and may also provide T cell help for efficient generation of NAb by HIV-specific B cells. We have demonstrated that a decline in this protective p24 response in slow progressors either preceded or coincided with classic signs of disease progression.