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Retrovirology

, 9:P254 | Cite as

Programmed Death-1(PD-1), a correlate of protection against disease progression in HIV-1 infected long-term non-progressors

  • J Kyosiimire-Lugemwa
Open Access
Poster presentation

Keywords

Viral Load Rapid Progressors Progression Marker Disease Progression Marker Plasma Lipopolysaccharide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Background

Long-Term Non-Progressors (LTNP) control HIV-1 disease progression but correlates of control are not clear. T-cell activation and expression of Programmed Death-1 (PD-1), a marker of T-cell inhibition/exhaustion, have been suggested as markers of progression to AIDS. We assessed levels of T-cell activation and PD-1 in LTNP and Rapid progressors (RP).

Methods

We recruited 15 LTNP and 15 RP originally enrolled in the Entebbe Cohort in Uganda. All were ART naïve and 29 were women. HLADR , CD38 and PD-1 levels were assessed in CD4, CD8 and CD45RA T-cells by flow cytometry. HIV-1 disease progression markers: plasma lipopolysaccharide (LPS) levels, HIV-1 RNA viral load (VL), HIV-1 pro-viral DNA load (PVL) and CD4 counts at enrollment were quantified. Comparisons between groups were performed using the Mann-Whitney U test and correlations by Spearman’s linear correlation coefficients.

Results

Activated (HLADR+CD38+) CD4+CD45RA+ were higher in the LTNP (median 0.64% for LTNP and 0.18% for RP, p=0.03). PD-1 expression in the CD4 and CD8 T-cell subsets was higher in the LTNP (CD4+PD-1+ median 39.6% for LTNP and 1.0% for RP, p=0.001; CD8+PD-1+ median 60.8% for LTNP and 13.5% for RP, p=0.003). VL (p=0.05), PVL (p=0.03), LPS (p=0.005) were higher in the RP and enrollment CD4 count (p=0.0002) was higher in the LTNP. VL, PVL and LPS positively associated with each other and all negatively associated with enrollment CD4 count. CD4+PD-1+ correlated negatively with VL (rs=-0.40, p=0.03), LPS (rs=-0.38, p=0.04) and positively with enrollment CD4 count (rs=0.36, p=0.05). CD4+CD45RA+HLADR+CD38+ correlated positively with enrollment CD4 counts (rs=0.38, p=0.04). Positive correlations were observed between CD4+CD45RA+/-HLADR+CD38+, CD8+CD45RA+HLADR+CD38+ and CD4+PD-1+ and CD8+PD-1+ T-cells.

Conclusion

Co-expression of PD-1 and activation markers was higher in the LTNP compared to the RP, contrary to other studies. PD-1 correlated with markers of protection against HIV-1 disease progression, suggesting a beneficial role for PD-1.

Copyright information

© Kyosiimire-Lugemwa; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Authors and Affiliations

  • J Kyosiimire-Lugemwa
    • 1
  1. 1.MRC/UVRI Uganda Research Unit on AIDSKampalaUganda

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