Abstract

Low levels of immune activation in viremic non-progressors HIV-infected individuals

J. Taaffe¹, B. Julg², B. Rodriguez³, S. Gordon⁴, I. Frank¹, D. Ripamonti⁵, A. Gori⁶, M. Lederman³, B. Walker², C. Torti⁷, G. Silvestri<sup>1,8

1</sup>University of Pennsylvania, Philadelphia, United States, ²Ragon Institute of MGH, MIT, and Harvard, Boston, United States, ³Case Western Reserve University, Cleveland, United States, ⁴National Cancer Insititute, Frederick, United States, ⁵Ospedali Riuniti, Bergamo, Italy, ⁶San Gerardo Hospital, Monza, Italy, ⁷University of Brescia, Brescia, Italy, ⁸Yerkes National Primate Research Center, Atlanta, United States

Background: In contrast to the majority of HIV-infected individuals, long-term non-progressors (LTNPs) maintain healthy CD4+ T-cell counts and do not progress to AIDS. These individuals typically have low or undetectable viremia, however, a small subset of LTNPs, hence-to-forth referred to as viremic non-progressors (VNPs), present with viremia comparable to normal progressors. VNPs are a largely uncharacterized patient population presenting a unique opportunity to study how progression to AIDS may be avoided despite robust virus replication. Given the role of chronic immune activation as a risk factor for progressive HIV infection, we hypothesized that the VNPs phenotype is associated with low levels of T-cell activation.
Methods: Archived cells from 7 VNP, 10 normal progressors, and 11 uninfected individuals were analyzed by flow cytometry for markers of T-cell activation. All normal progressors and VNPs had viral loads in excess of 30,000 RNA copies/mL, but VNPs were defined by having little to no CD4+ T-cell loss over time.
Results: VNPs and progressors, respectively, had a mean viral load of 53,517 and 74,133 RNA copies/mL, and a mean CD4+ T-cell slope of 7.65 and -64.48 cells/year with respect to baseline, as calculated by linear regression. Multicolor flow cytometric analysis revealed that, in VNPs, the fraction of CD4+ and CD8+ T-cells expressing markers of activation and proliferation, including HLA-DR, CD38, CD69, and Ki67, were lower than those from normal progressors.
Conclusions: The preliminary results of this study indicate that VNPs have lower levels of T-cell activation in comparison to normal progressors, despite similarly high viremia. Overall these data are consistent with the hypothesis that low levels of T-cell activation are a feature, and possibly a determinant, of the VNP phenotype during HIV infection. The results of this study encourage further investigation into the immunological and virological signatures of HIV-infected individuals with the VNP phenotype.