Nichole R. Klatt 1 , 2 , * , Steven E. Bosinger 3 , Melicent Peck 4 , Laura E. Richert-Spuhler 1 , Anke Heigele 5 , Jillian P. Gile 1 , Nirav Patel 3 , Jessica Taaffe 3 , Boris Julg 6 , David Camerini 7 , Carlo Torti 8 , Jeffrey N. Martin 4 , Steven G. Deeks 4 , Elizabeth Sinclair 4 , Frederick M. Hecht 4 , Michael M. Lederman 9 , Mirko Paiardini 3 , Frank Kirchhoff 5 , Jason M. Brenchley 2 , Peter W. Hunt 4 , Guido Silvestri 3
28 August 2014
A rare subset of HIV-infected individuals, designated viremic non-progressors (VNP), remain asymptomatic and maintain normal levels of CD4+ T-cells despite persistently high viremia. To identify mechanisms potentially responsible for the VNP phenotype, we compared VNPs (average >9 years of HIV infection) to HIV-infected individuals who have similar CD4+ T-cell counts and viral load, but who are likely to progress if left untreated (“putative progressors”, PP), thus avoiding the confounding effect of differences related to substantial CD4+ T cell depletion. We found that VNPs, compared to PPs, had preserved levels of CD4+ stem cell memory cells (T SCM ( p<0.0001), which was associated with decreased HIV infection of these cells in VNPs (r = −0.649, p = 0.019). In addition, VNPs had decreased HIV infection in CD4+ central memory (T CM) cells ( p = 0.035), and the total number of T CM cells was associated with increased proliferation of memory CD4+ T cells (r = 0.733, p = 0.01). Our results suggest that, in HIV-infected VNPs, decreased infection of CD4+ T CM and T SCM, cells are involved in preservation of CD4+ T cell homeostasis and lack of disease progression despite high viremia.
Here we assessed correlates of protection from disease progression in a rare subset of HIV-infected individuals, viremic non-progressors (VNP). These individuals have high viral load for several years. In contrast to the majority of infected individuals, however, these individuals do not progress to AIDS. Here we found this lack of progression was associated with selective preservation of two critical subsets of memory CD4+ T cells, central memory (T CM) and stem-cell memory (T SCM) cells. Compared to HIV-infected putative progressors, VNPs had higher proliferation of these indispensable subsets of memory cells. In addition, the long-lived CD4+ T CM and T SCM cells in VNPs had decreased HIV infection compared to the less critical effector memory CD4+ T cells, which indicates a possible mechanism by which VNPs maintain their CD4+ T cell pool after several years of infection, and remain free from AIDS progression.