Background:  Recently, much attention has shifted toward the development of therapeutic vaccines in an attempt to boost the immune system's control of HIV-1. However, this has been hampered by the inability to identify conserved antigenic determinants to which responses should be directed and because in chronic HIV-1 infection anti-HIV-1 immune responses remain poor. Long-term non-progressors (LTNP) represent a group of HIV-1-infected patients who have very slow (or no) disease progression with high CD4 T-cell counts and very low or undetectable viral loads after many years of infection. These patients represent a group in whom the immune response to HIV-1 appears to be preserved. Therefore, analysis of altered viro-immunopathology in these patients becomes imperative.

Methods:  A prospective analysis was undertaken of CD4 T cell proliferative responses in 41 HIV-1⁺ individuals originally identified as LTNP in 1996. A comparison was made between persons who were still LTNP and patients that had progressed. All statistical analyses were performed using nonparametric methods.

Results:  To date, of the 41 patients defined in the 1996 cohort, 35 had progressed, 29 of whom are now receiving HAART. Of these 29, 23 were started on HAART as they fulfilled the BHIVA guidelines of CD4 T-cell count <350 cells/µL and/or viral load >30,000 copies/mL. The remaining 6 treated patients developed recurrent infections and were recommended HAART by their regular clinic doctors. The 6 progressing patients not currently on HAART have been regularly reviewed and show signs of falling CD4 T-cell counts, and are likely to need therapy in due course. Unlike the progressing patients, the 6 remaining LTNP have maintained good HIV-1-specific CD4 T-cell proliferative responses to both regulatory Nef and Tat, and structural Gag p24 and Env gp120 proteins.

Conclusions:  This study demonstrates that elite controllers direct a CD4⁺ T cell-specific-proliferative response to a wide range of both regulatory and structural HIV-1 proteins in addition to the Gag-specific responses, which are signatory of LTNP. Detailed comparative genetic and immunological studies of HIV-1-specific immune function and dysfunction, in both CD4 and CD8 T cells, observed in the very small cohorts of elite controllers versus chronically infected patients are essential when investigating correlates of protection to HIV-1.