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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e31824c17c4
Clinical Science

Gene Expression Profiles Predict Emergence of Psychiatric Adverse Events in HIV/HCV-Coinfected Patients on Interferon-Based HCV Therapy

Rasimas, Joseph MD, PhD*,†; Katsounas, Antonios MD, PhD‡,§; Raza, Haniya MD*,‖; Murphy, Alison A. BA; Yang, Jun PhD; Lempicki, Richard A. PhD; Osinusi, Anu MD, MPH¶,#; Masur, Henry MD**; Polis, Michael MD; Kottilil, Shyam MD, PhD; Rosenstein, Donald MD*,††

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In the article by Rasimas et al, appearing in JAIDS: Journal of Acquired Immune Deficiency Syndromes, Vol. 60, No. 3, pp. 273-281, entitled “Gene Expression Profiles Predict Emergence of Psychiatric Adverse Events in HIV/HCV-Coinfected Patients on Interferon-Based HCV Therapy”, it should have been indicated that Joseph Rasimas, MD, PhD, and Antonios Katsounas, MD, PhD are considered as co-first authors of the article, since they contributed equally to the manuscript.

JAIDS Journal of Acquired Immune Deficiency Syndromes. 60(5):e122, August 15, 2012.

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Background: The efficacy of pegylated interferon-α and ribavirin (pegIFN/RBV) in the treatment of Hepatitis C infection is limited by psychiatric adverse effects (IFN-PE). Our study examined the ability of differential gene expression patterns before therapy to predict emergent IFN-PE among 28 HIV/HCV-coinfected patients treated with pegIFN-α2b/RBV.

Methods: Patients dually infected with HIV and HCV were evaluated at baseline and during treatment by board-certified psychiatrists who classified patients into 2 groups: those who developed IFN-PE and those who did not (IFN-NPE). Gene expression analysis (Affymetrix HG-U133A) was performed using peripheral blood mononuclear cells before and after initiation of treatment. Analysis of Variance, post hoc analysis based on pair-wise comparisons, and functional annotation analysis identified differentially expressed genes within and between groups. Prediction analysis for microarrays was used to test the predictive ability of selected genes.

Results: Twenty-four genes (16 upregulated and 8 downregulated) that were differentially expressed at baseline in patients who subsequently developed IFN-PE compared with the IFN-NPE group showed the ability to predict IFN-PE with an accuracy of 82%. In 16 patients with IFN-PE, 135 genes (117 upregulated; 18 downregulated) were significantly modulated after treatment. Of these, 10 genes have already been shown to be associated with neuropsychiatric illnesses and were significantly modulated only in patients who experienced IFN-PE.

Conclusions: We describe a novel molecular diagnostic biomarker panel to predict emergent IFN-PE in HIV/HCV-coinfected patients undergoing pegIFN/RBV treatment, which may improve the identification of patients at greatest risk for IFN-PE and suggest candidate therapeutic targets for preventing or treating IFN-PE.

© 2012 Lippincott Williams & Wilkins, Inc.


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