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Volume 6 Supplement 3

AIDS Vaccine 2009

P16-16. Gag and Nef specific T-cell responses in HIV-1 infected long-term non-progressors in Uganda

Background

HIV-1-specific T-cell responses are preserved in HIV-1 infected individuals with non-progressing HIV-1 disease. ''Long Term Non Progressors'' (LTNPs) were defined as ART naive individuals infected with HIV-1 for >8 years, maintaining CD4+ T-cell counts >500, and with minimal CD4+ decline over time. We tested the hypothesis that Gag-specific T-cell responses are inversely correlated to disease progression whereas Nef-specific T-cell responses are not.

Methods

17 ART naïve HIV-1 infected patients from the Entebbe cohort in Uganda were recruited and stratified by CD4+ T-cell count, CD4+ decline slopes, and time of enrolment, into 2 groups – 10 LTNP and 7 Rapid progressors (RP). All patients were women. We measured plasma viral load, current CD4 T-cell count, and IFN-γ, IL-2, IL-4 and perforin ELISpot responses to pools of 22 to 34 peptides (18-mers overlapping by 10 aa) based on consensus sequences of Gag and Nef from HIV-1 clades A1, A2 and D. Medians and inter-quartile ranges were calculated and comparisons between groups were performed using the Mann-Whitney U test. Correlations were presented using Spearmann's linear correlation coefficients.

Results

IFN-γ responses to GagA2 pool1 were significantly higher in the LTNP than in RP (p = 0.02). IL-4 responses to the GagA2 pool2 were higher in LTNP (p = 0.07), whilst perforin responses to the same pool were higher in the RP (p = 0.06). IL-2 responses were low and not significantly different between LTNP and RP. IFN-γ, IL-4 or perforin responses did not correlate with CD4 T-cell counts or viral load. All responses to Nef peptides were not significantly different between the LTNP and RP.

Conclusion

IFN-γ Gag HIV-1 specific responses were higher in LTNPs than in RPs confirming previous results. Higher perforin responses seen in RP perhaps indicate accelerated elimination of infected target cells. Non-specific IL-4 responses were high possibly reflecting TH2 responses to common environmental pathogens in the study population.

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Correspondence to J Kyosiimire-Lugemwa.

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

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Kyosiimire-Lugemwa, J., Pala, P., Miiro, G. et al. P16-16. Gag and Nef specific T-cell responses in HIV-1 infected long-term non-progressors in Uganda. Retrovirology 6, P245 (2009). https://doi.org/10.1186/1742-4690-6-S3-P245

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Keywords

  • Rapid Progressors
  • Plasma Viral Load
  • Infected Target Cell
  • ELISpot Response
  • Accelerate Elimination