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

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.