Limited HIV infection of central memory and stem cell memory CD4+ T cells is associated with lack of progression in viremic individuals.
2014
Nichole R Klatt | Steven E Bosinger | Melicent Peck | Laura E Richert-Spuhler | Anke Heigele | Jillian P Gile | Nirav Patel | Jessica Taaffe | Boris Julg | David Camerini | Carlo Torti | Jeffrey N Martin | Steven G Deeks | Elizabeth Sinclair | Frederick M Hecht | Michael M Lederman | Mirko Paiardini | Frank Kirchhoff | Jason M Brenchley | Peter W Hunt | Guido Silvestri
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.
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