Neopterin Predicts Disease Progression in Advanced HIV-1 Infection

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By Megan Rauscher

Elevated serum levels of neopterin, a marker of immune activation, is a robust independent predictor of disease progression in patients with advanced HIV-1 infection, researchers report in the March 15th issue of Clinical Infectious Diseases.

Neopterin is a "simple, inexpensive marker that is routinely available, and it could be a very useful marker for monitoring patients in resource-limited settings where T cell counts and HIV-1 RNA levels may not be readily available," Dr. Donna Mildvan from Beth Israel Medical Center in New York noted in a telephone interview with Reuters Health.

In the United States, neopterin is "an attractive adjunct to RNA and CD4 counts as it has the potential to offer a snapshot of yet another element of pathophysiology; and the more you know about a patient the more intelligent your decisions can be in terms of management," she added.

Dr. Mildvan and her colleagues validated the prognostic value of neopterin for HIV-1 disease progression by analyzing clinical and laboratory data and stored frozen serum samples from 152 patients in the ACTG 116B/117 trial. This randomized study demonstrated the benefit of didanosine over zidovudine monotherapy for advanced HIV-1 infection.

During a median of 344 days follow-up, elevated baseline levels of neopterin, as well as endogenous interferon, and interleukin-6 were each associated with an increased risk of clinical disease progression, they report.

For neopterin, the hazard ratio for disease progression was 2.94 in subjects with baseline levels of 21.1 compared with 11.4 nmol/L (the 75th and 25th percentiles, respectively).

For interferon, the hazard ratio was 1.4 in subjects with baseline levels of 26 compared with 10 international units, again the 75th and 25th percentiles, respectively. And for IL-6, the hazard ratio for disease progression was 2.07 for subjects with values of 74.8 compared with 16.0 nmol/L, again the 75th and 25th percentiles.

In analyses adjusted for CD4+ T cell count and HIV-1 RNA level, elevated serum neopterin (p = 0.0002), and to a lesser extent, endogenous interferon (p = 0.0053), were the strongest predictors of clinical disease progression 6 months later.

These data show that "soluble markers of immune activation add prognostic information to CD4 counts and viral load for risk of disease progression in advanced HIV-1 infection," Dr. Mildvan and colleagues write.

These findings support a previous study, (see Reuters Health report August 4, 1998), which showed that several markers of immune activation -- specifically, levels of tumor necrosis factor receptor II, interleukin-2 receptor, beta-2-microglobulin and neopterin -- all rose about 6 months prior to a sharp decline in CD4 cell count and an increase in HIV viral replication.

03/14/05

Clin Infect Dis 2005;40:853-858.