Nichole R Klatt 1 , Steven E Bosinger 2 , Melicent Peck 3 , Laura E Richert-Spuhler 4 , Anke Heigele 5 , Jillian P Gile 4 , Nirav Patel 2 , Jessica Taaffe 2 , Boris Julg 6 , David Camerini 7 , Carlo Torti 8 , Jeffrey N Martin 3 , Steven G Deeks 3 , Elizabeth Sinclair 3 , Frederick M Hecht 3 , Michael M Lederman 9 , Mirko Paiardini 2 , Frank Kirchhoff 5 , Jason M Brenchley 10 , Peter W Hunt 3 , Guido Silvestri 2
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 (TSCM (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 (TCM) cells (p = 0.035), and the total number of TCM 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+ TCM and TSCM, cells are involved in preservation of CD4+ T cell homeostasis and lack of disease progression despite high viremia.