TY - JOUR T1 - Serum neopterin, an immune activation marker, independently predicts disease progression in advanced HIV-1 infection. AU - Mildvan,Donna, AU - Spritzler,John, AU - Grossberg,Sidney E, AU - Fahey,John L, AU - Johnston,David M, AU - Schock,Barbara R, AU - Kagan,Jonathan, Y1 - 2005/02/18/ PY - 2004/06/30/received PY - 2004/10/22/accepted PY - 2005/3/1/pubmed PY - 2006/8/10/medline PY - 2005/3/1/entrez SP - 853 EP - 8 JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin Infect Dis VL - 40 IS - 6 N2 - 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. SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/15736019/Serum_neopterin_an_immune_activation_marker_independently_predicts_disease_progression_in_advanced_HIV_1_infection_ DB - PRIME DP - Unbound Medicine ER -