Immunologic and virologic evolution during periods of intermittent and persistent low-level viremia

Annika C. Karlsson, Sophie R. Younger, Jeffrey N. Martin, Zvi Grossman, Elizabeth Sinclair, Peter W. Hunt, Elilta Hagos, Douglas F. Nixon, Steven G. Deeks*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: HIV replication, HIV-specific T-cell responses and T-cell activation each contributes to disease outcome during untreated HIV infection. The interaction of these factors is not well understood, particularly in the setting of antiretroviral therapy. Methods: This is a longitudinal study of antiretroviral-treated patients with plasma HIV RNA levels < 1000 copies/ml. Patients were divided into three groups: suppressed viremia, intermittent viremia ('blips') and persistent low-level viremia. HIV-specific immunity was measured using interferon-γ ELISPOT. T-cell activation was defined by CD38 and HLA-DR co-expression. Drug resistance was quantified using a phenotypic susceptibility assay. Results: The breadth and the magnitude of the HIV-specific CD8 T-cell response was greater in patients with either intermittent or persistent viremia compared to patients with suppressed viremia. In contrast, T-cell activation was significantly elevated only in those patients with persistent viremia. Patients with persistent low-level viremia had moderate levels of phenotypic antiretroviral drug resistance that increased over time. Virologic failure (confirmed increase in viral load > 1000 HIV RNA copies/ml) was primarily observed in the persistently viremic group. Conclusions: Antiretroviral-treated individuals with intermittent viremia appear to mount an effective HIV-specific T-cell response while not experiencing increases in the level of immune activation. This may limit viral evolution and emergence of drug resistance. In contrast, antiretroviral-treated individuals with persistent low-level viremia exhibit significant increases in overall immune activation and a substantial risk of subsequent treatment failure. It is likely that higher viremia and stronger immune activation act synergistically to accelerate the development of systemic drug resistance.

Original languageEnglish
Pages (from-to)981-989
Number of pages9
JournalAIDS
Volume18
Issue number7
DOIs
StatePublished - 30 Apr 2004

Keywords

  • Antiretroviral therapy
  • HIV drug resistance/resistance mutations
  • HIV-specific cellular immunity
  • Immune activation

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