Background
Neopterin, a biomarker of immune activation, has been widely studied in cerebrospinal fluid as a correlate of neuroinflammation and neurocognitive impairment (NCI) in people with HIV (PWH). Recent evidence suggests that plasma neopterin could be useful in identifying PWH at risk of developing NCI. This study explores neopterin as a potential plasma biomarker for NCI using 3 different cognitive screening measures in aging PWH.
Methods
One hundred PWH attended at Germans Trias i Pujol Hospital, Spain, aged ≥50 years, on ART, with plasma HIV-1 RNA levels <50 copies/ml (≤6 months), were randomly selected to participate in the ALI Study (Exploring Suggestive Symptoms of Preclinical Alzheimer’s Disease in People with HIV; IRB approval: PI-21-003). A control group of 50 HIV-negative volunteers, matched for age, sex, and education level, was also enrolled. All participants were cognitively assessed using 3 screening tools: Mini-Mental State Examination (MMSE), FACEmemory, and NEU Screen. Plasma neopterin levels were measured by ELISA and were compared between groups and according to cognitive screening classifications. Statistical tests included the Chi-square test for categorical variables and the Mann-Whitney U test for continuous variables.
Results
Most participants were men (73%), with a mean age of 60 (±8) years, and 11 (±4) years of formal education. Positive screening for NCI was more prevalent in PWH than in controls according to the 3 screening methods, reaching statistical signification only with the NEU Screen: MMSE: 14% vs 6%, p=0.145; FACEmemory: 70% vs 56%, p=0.095; and NEU Screen: 37% vs 16%, p=0.009. Neopterin levels were higher in PWH compared to controls: 6.21 ng/ml (IQR: 3.26 – 9.14) vs 3.54 ng/ml (IQR: 2.99 – 4.82), p=0.001. Neopterin levels were also significantly higher in participants with suspected NCI compared to those without, only when using the NEU Screen classification (see Figure).
Conclusions
The higher levels of plasma neopterin observed in aging PWH compared to HIV-negative individuals suggest persistent immune activation despite effective ART. Elevated neopterin levels were significantly associated with suspected NCI as measured by the NEU Screen. These results reinforce the NEU Screen as a useful NCI screening test in HIV infection, and, additionally, underscore the potential utility of neopterin as a plasma biomarker for cognitive decline in aging PWH.