Serum neopterin, an immune activation marker, independently predicts disease progression in advanced HIV-1 infection.

Abstract

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 beta2-microglobulin, neopterin, endogenous interferon, triglycerides, interleukin-6, soluble tumor necrosis factor- alpha 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.

• Authors: Donna Mildvan, John Spritzler, Sidney E Grossberg, John L Fahey, David M Johnston, Barbara R Schock, Jonathan Kagan
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 40 Issue 6 Pg. 853-8 (Mar 15 2005) ISSN: 1537-6591 [Electronic] United States
• PMID: 15736019 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-HIV Agents
• Biomarkers
• Interleukin-6
• Zidovudine
• Neopterin
• Interferons
• Didanosine

Topics

• Anti-HIV Agents (therapeutic use)
• Biomarkers
• CD4 Lymphocyte Count
• Didanosine (therapeutic use)
• Disease Progression
• Dose-Response Relationship, Drug
• Female
• HIV Infections (blood, diagnosis, drug therapy)
• Humans
• Interferons
• Interleukin-6
• Male
• Neopterin (blood)
• Predictive Value of Tests
• Risk Factors
• Zidovudine (therapeutic use)