Urinary Neopterin Indicates Early Infection and Disease Progression: Model Studies with Simian and Human Immunodeficiency Viruses in Macaques

Abstract

Abstract The value of urinary neopterin as a predictive marker for disease progression in SIV- and HIV-2-infected rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis) was assessed by comparing pre- with postinfection data. Before infection stable baselines for neopterin were observed in both species with significantly higher concentrations in cynomolgus macaques than in rhesus macaques. After infection of cynomolgus macaques with human immunodeficiency virus type 2 (HIV-2) neopterin concentrations exceeded 1.2 - 4.2 times preinfection values, whereas rhesus monkeys infected with simian immunodeficiency virus (SIV) yielded concentrations of more than 8 times above baseline. Increased neopterin concentrations always preceded seroconversion. No rise of neopterin was observed in cynomolgus macaques remaining seronegative after inoculation with HIV-2, whereas after inoculation with SIV neopterin was slightly elevated in rhesus monkeys despite remaining seronegative. In animals with high virus replication a pronounced increase of neopterin levels was followed by signs of immunodeficiency. Therefore like in HIV-1-infected man, in macaques infected with SIV or HIV-2 the urinary neopterin concentration is an early and reliably predictive marker for AIDS disease progression and reflects pathogenicity. This parameter can be easily assessed in study protocols for drug and vaccine tests in monkeys as in man.