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
N1 - Funding Information:
Financial support. This work was supported in part by the Adult ACTG, funded by the National Institute of Allergy and Infectious Diseases (grants AI-38858, AI-46370, AI-38855, and AI36086). Potential conflicts of interest. All authors: no conflicts.
PY - 2005/3/15
Y1 - 2005/3/15
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 β2- 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.
AB - 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 β2- 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.
UR - http://www.scopus.com/inward/record.url?scp=14944375950&partnerID=8YFLogxK
U2 - 10.1086/427877
DO - 10.1086/427877
M3 - Article
C2 - 15736019
AN - SCOPUS:14944375950
SN - 1058-4838
VL - 40
SP - 853
EP - 858
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 6
ER -