Background:  Host immune activation is a critical factor in systemic disease progression in HIV/AIDS and in the development of the AIDS dementia complex (ADC). Cerebrospinal fluid (CSF) neopterin, derived from activated macrophages and microglia, reflects intrathecal immunoactivation. We undertook a study of HIV-infected subjects to test the hypothesis that CSF neopterin concentrations are reduced in subjects treated with ART, even in the setting of continued plasma viremia (treatment failure). 

Methods:  Cross-sectional study of 139 HIV-infected subjects categorized by treatment status and HIV RNA viral load:  57 not taking ART for  ³4 months; 35 on ART with plasma viral load > 500 copies/mL (failures); and 47 on ART with plasma viral load <500 copies/mL (successes); 48 HIV­ subjects served as controls. Neopterin was measured by the ELItest Neopterin EIA. Results were analyzed with the 1-way ANOVA, followed by the Tukey test for multiple comparisons. 

Results:  Age, gender, and CD4 count did not differ between the HIV-infected groups. Median CSF neopterin in the failures was 10 nmol/L (IQR 6.9 to 14.4) and in successes was 6.7 nmol/L (IQR 5.2 to 10.1); compared with levels in untreated subjects of 16.8 nmol/L (IQR 11.1 to 29.7), these were each significantly different (p = 0.000, Tukey test). Results for blood neopterin were similar except that levels in failures were not significantly lower than those not taking ART for ³4 months (p = 0.093). The reduction of CSF neopterin in failures compared with those not taking ART was present across the range of plasma HIV viral load, whereas CSF neopterin correlated directly with the CSF viral load in these 2 groups (r² = 0.503, p <0.001).

Conclusions:  ART that fails to completely suppress systemic HIV down-regulates local macrophage activation in the central nervous system, though not to the degree noted in those with complete viral suppression. This may be related to direct antiviral drug effect on central nervous system infection and consequent local activation within the central nervous system or to reduced systemic immune activation and viral traffic into the CSF and brain. The inhibition of intrathecal immune activation by ART, even in the absence of complete plasma HIV suppression, may contribute to preventing or ameliorating the neuropathogenic processes underlying ADC.