Journal Article

Serum Neopterin, an Immune Activation Marker, Independently Predicts Disease Progression in Advanced HIV-1 Infection

Donna Mildvan, John Spritzler, Sidney E. Grossberg, John L. Fahey, David M. Johnston, Barbara R. Schock and Jonathan Kagan

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 40, issue 6, pages 853-858
Published in print March 2005 | ISSN: 1058-4838
Published online March 2005 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/427877
Serum Neopterin, an Immune Activation Marker, Independently Predicts Disease Progression in Advanced HIV-1 Infection

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Background. CD4+ T lymphocyte (CD4) counts and plasma human immunodeficiency virus (HIV) type 1 RNA concentrations predict clinical outcome in HIV-1 infection. Our objective was to assess the independent prognostic value for disease progression of soluble markers of immune system activation.

Methods. This retrospective marker-validation study utilized previously obtained clinical and laboratory data, including CD4+ cell counts, and made use of stored frozen serum samples to assay for levels of β-microglobulin, neopterin, endogenous interferon, triglycerides, interleukin-6, soluble tumor necrosis factor-α receptor II, and HIV-1 RNA, and to determine HIV genotypic reverse-transcriptase inhibitor resistance. The 152 patients who participated in this study represented a subsample of participants in AIDS Clinical Trials Group (ACTG) 116B/117, a randomized trial that demonstrated the clinical benefit of didanosine over zidovudine monotherapy in persons with advanced HIV-1 infection. Marker data were analyzed in relation to protocol-defined clinical disease progression, using Cox proportional hazards models.

Results. The median duration of follow-up was 344 days. Elevated baseline values for neopterin (P =.0009), endogenous interferon (P =.00039) and interleukin-6 (P =.0007) were each associated with greater subsequent risk of clinical disease progression. In a head-to-head comparison that was adjusted for CD4+ cell count (P =.0165) and HIV-1 RNA level (P =.1220), we found that elevated values for neopterin (P =.0002) and, to a lesser extent, endogenous interferon (P =.0053) were the strongest predictors of increased risk of clinical disease progression 6 months later.

Conclusions. Soluble markers of immune activation add prognostic information to CD4 counts and viral load for risk of disease progression in advanced HIV-1 infection. The robust performance of neopterin, an inexpensive and reliably measured serum marker, supports its potential suitability for patient monitoring, particularly in resource-limited settings.

Journal Article.  4477 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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