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. Silvestri1,8
1University 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
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