Serum neopterin, an immune activation marker, independently predicts disease progression in advanced HIV-1 infection.
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.
Mildvan
Donna
D
Beth Israel Medical Center, New York, New York 10003, USA. mildvan@ix.netcom.com
Spritzler
John
J
Grossberg
Sidney E
SE
Fahey
John L
JL
Johnston
David M
DM
Schock
Barbara R
BR
Kagan
Jonathan
J
D019380:Anti-HIV Agents / Q000627:therapeutic use; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000627:therapeutic use; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D007372:Interferons; D015850:Interleukin-6; D008297:Male; D019798:Neopterin / Q000097:blood*; D011237:Predictive Value of Tests; D012307:Risk Factors; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015415:Biomarkers; D015850:Interleukin-6; D015215:Zidovudine; D019798:Neopterin; D007372:Interferons; D016049:Didanosine