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NK Response Correlates with HIV Decrease in Pegylated IFN-α2a-Treated Antiretroviral Therapy-Suppressed Subjects.

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Pegylated interferon-alfa-2a (Peg-IFN-α2a) enhances antiretroviral therapy (ART) for HIV control. Increased innate immune activity and NK cell cytotoxicity correlate with Peg-IFN-α2a

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Area of Science:

  • Immunology
  • Virology
  • Genetics

Background:

  • Previous studies showed pegylated interferon-alfa-2a (Peg-IFN-α2a) with antiretroviral therapy (ART) suppressed HIV and reduced integrated HIV DNA.
  • The mechanisms underlying this viral control, particularly the role of innate immunity, require further investigation.

Purpose of the Study:

  • To evaluate the association between innate NK cell activity, peripheral blood mononuclear cell (PBMC) transcriptional profiles, and decreases in HIV measures.
  • To identify correlates of Peg-IFN-α2a-mediated HIV control.

Main Methods:

  • Analysis of human peripheral blood at baseline (ART), after 5 weeks of ART+Peg-IFN-α2a, and after 12 weeks of Peg-IFN-α2a monotherapy.
  • Assessment of immune subset frequencies, IFN-stimulated gene induction, microRNA expression, NK cell activity, and PBMC transcriptional profiles.

Main Results:

  • Preserved immune subset frequencies and induced IFN-stimulated genes were observed, except in a subset with increased microRNA expression.
  • Viral control correlated with higher NK cell activity, IP-10 levels, downmodulation of KIR expression, and enhanced NK cytotoxicity.
  • Integrated HIV DNA decline was associated with gene expression patterns indicating cell-mediated activation and NK cytotoxicity.

Conclusions:

  • Increased innate immune activity and NK cell cytotoxicity are key correlates of Peg-IFN-α2a-mediated HIV control.
  • PBMC transcriptional profiles and NK cell function provide insights into the efficacy of Peg-IFN-α2a in HIV treatment.