HIV-1 invades the central nervous system (CNS) in the context of acute
infection, persists thereafter in the absence of treatment, and leads to chronic intrathecal immunoactivation that can be measured by the macrophage activation marker,
neopterin, in cerebrospinal fluid (CSF). In this review we describe our experience with CSF
neopterin measurements in 382 untreated HIV-infected patients across the spectrum of immunosuppression and HIV-related neurological diseases, in 73 untreated
AIDS patients with opportunistic
CNS infections, and in 233 treated patients.In untreated patients, CSF
neopterin concentrations are almost always elevated and increase progressively as immunosuppression worsens and blood CD4 cell counts fall. However, patients with
HIV dementia exhibit particularly high CSF
neopterin concentrations, above those of patients without neurological disease, though patients with CNS
opportunistic infections, including CMV
encephalitis and
cryptococcal meningitis, also exhibit high levels of CSF
neopterin.
Combination antiretroviral therapy, with its potent effect on CNS
HIV infection and CSF HIV
RNA, mitigates both intrathecal immunoactivation and lowers CSF
neopterin. However, despite suppression of plasma and CSF HIV
RNA to below the detection limits of clinical assays (<50 copies HIV
RNA/mL), CSF
neopterin often remains mildly elevated, indicating persistent low-level intrathecal immune activation and raising the important questions of whether this elevation is driven by continued
CNS infection and whether it causes continued indolent CNS injury.Although nonspecific, CSF
neopterin can serve as a useful
biomarker in the diagnosis of
HIV dementia in the setting of confounding conditions, in monitoring the CNS inflammatory effects of antiretroviral treatment, and give valuable information to the cause of ongoing
brain injury.