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

What is the key factor that sustains a non-progressive disease course, and what initiates the decline in protective immunity after many years of a non-progressive disease course. Could a change in viral pathogenicity overcome this delicate balance between host and virus, or could progressive weakening of the CD4 T cell response by slow virus turnover gradually allow the virus to escape the combined effector mechanisms of the HIV-specific cell-mediated and humoral immune responses? Escape mutants at the B27 epitope KRWIILGLNK have been observed under conditions of high viral load and evolutionary drift [34] , which was likely in C117, but not for both C13 and C122, who had prolonged periods of immune control in the presence of p24 proliferative responses, and very low viraemia up to or beyond the second decade of HIV infection. Disease progression in one SBBC member (C98) and the SBBC infecting donor was associated with the emergence of divergent strains which preceded viral load increases and subsequent changes in immune responses [39, 40] . Also, these individuals lacked protective p24 proliferative responses and had detectable viraemia before viral divergence occurred, providing further evidence that effective immune control over viral replication to levels below a putative threshold, may prevent the emergence of escape mutants or fitter variants. Therefore, the common factor in all these observations is the decline or lack of p24 proliferative responses, suggesting that a lack of helper T cell responses may result in a reduced capacity to contain viral replication by other immune effector responses including CTL, independent of the presence of viral escape mutants.