HIV viral set point and host immune control in individuals with HIV-specific CD8+ T-cell responses prior to HIV acquisition

Rupert Kaul, Kelly S. MacDonald, Nico J. Nagelkerke, Joshua Kimani, Keith Fowke, T. Blake Ball, Ma Luo, Anthony Kariri, Walter Jaoko, Stephen Moses, Sarah Rowland-Jones, Francis A. Plummer

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Objective: Vaccine-induced CD8+ T-cell responses in primates have been associated with a reduced simian immunodeficiency virus plasma viral load and enhanced T-cell responses, but cellular vaccines have shown limited success in human trials. We previously described HIV-specific T-cell responses in two groups of highly exposed, persistently seronegative Kenyan female sex workers, and a subset of these participants have subsequently acquired HIV. We examined the impact of pre-existing CD8+ T-cell responses on post-acquisition outcomes. Design and Methods: HIV-specific CD8+ T-cell responses had been examined in highly exposed, persistently seronegative participants from the Pumwani and Kibera cohorts, using a combination of virus-specific lysis, proliferation, interferon-gamma production, or all. Plasma viral load set point and HIV-specific T-cell proliferation and cytokine production were now examined post hoc by blinded investigators in the subset of participants who acquired HIV. Results: Pre-acquisition cellular immune assays and post-infection viral load were available for 46 participants, and HIV-specific CD8+ T-cell responses had been detected in 25 of 46 (54%) participants. Pre-acquisition CD8+ T-cell responses were associated with a lower post-acquisition HIV viral load set point in both cohorts (pooled analysis, 3.1 vs. 4.1 log10 RNA copies/ml; P = 0.0002) and with enhanced post-acquisition HIV-specific CD8+ T-cell proliferation (3.8 vs. 1.0%, P = 0.03), but with a trend to reduced post-acquisition CD8+ T-cell interferon-gamma responses. Conclusion: HIV-specific CD8+ T-cell responses prior to HIV acquisition were associated with a lower HIV viral load and an altered functional profile of post-acquisition CD8+ T-cell responses.

Original languageEnglish
Pages (from-to)1449-1454
Number of pages6
JournalAIDS
Volume24
Issue number10
DOIs
Publication statusPublished - Jun 19 2010

Keywords

  • CD8 T cell
  • HIV
  • female sex worker
  • highly exposed
  • immune control
  • persistently seronegative
  • viral load

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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