Table 1.
Immunological and imaging biomarkers with recommended strengths.
| Approach | Indicator | Key findings | Recommended strength | |
|---|---|---|---|---|
| Immunological biomarkers in blood and CSF | Immune cells | lymphocytes | In HAND patients, blood CD4 + and CD8 + T cells exhibit active viral transcription (62, 64). Compared to blood, the frequency of dendritic cells in the cerebrospinal fluid of people with HIV (PWH) is increased, while the frequencies of B cells and natural killer (NK) cells are decreased (68). | Moderate |
| Myeloid lineage cells | Monocyte and macrophage populations are increased (69, 71). Compared to blood, cerebrospinal fluid (CSF) contains a higher proportion of CD8 + T cells and microglia-like cells (72, 73). | Moderate | ||
| Cytokines | Specific monocyte activation markers in blood and cerebrospinal fluid, such as elevated levels of new methotrexate, sCD163, and sCD14, along with neuroinflammation markers, including increased levels of IFN-γ, IL-1α, IL-7, IL-8, and sTNFR-II, as well as decreased levels of IL-6, demonstrate a consistent association with HIV-related neurocognitive impairment (49). | Moderate | ||
| Complement | In HIV patients, levels of C3 protein, CD55, CD59, C9, C5L2, C5aR, and C3aR are elevated (66, 122, 124). | Moderate | ||
| Immunoglobulins and antigens | HIV proteins Tat, gp120, and Nef are closely associated with HAND, and patients with HAND exhibit inflammatory changes in their brain antibody profiles (133–135). | Moderate | ||
| Others | Elevated concentrations of neurofilament light chain protein (NFL), new methotrexate, extracellular vesicles, β-amyloid, tau protein, and S100B protein are closely associated with poorer neuropsychological performance (30, 78, 80, 138, 143, 146). | Moderate | ||
| CT | Macroscopic brain structure | Diffuse brain atrophy inconsistent with age in individuals with HIV (165). | Weak | |
| MRI | 3D- TIWI | Microscopic brain gray matter structure (volume, cortical thickness, etc.) | Reduced volume of the frontal lobe and caudate/putamen is associated with the disease itself and neurocognitive impairments (171, 172). | Strong |
| DTI | Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) | Significantly increased MD and decreased FA in the right corpus callosum, corona radiata, internal capsule, and posterior thalamus are significantly associated with poorer cognitive performance (178, 180–182). | Strong | |
| rsfMRI | BOLD signal | Alterations in global brain topology are observed, with significant reductions in the significance and connectivity of the executive network (190–192). | Strong | |
| Task-based MRI | / | Different task difficulties activate distinct brain regions, and abnormal activation may reflect a compensatory mechanism (194, 196–199). | Strong | |
| MRS | NAA Peak, Glu Peak, Cho Peak, MI Peak, etc. | Decreased NAA and elevated Cho and MI levels are primarily observed in the frontal white matter and basal ganglia. Prolonged duration of HIV infection is associated with reduced NAA levels in the caudate nucleus (201–208). | Strong | |
| Radioisotopes | [18F]-FDG PET | SUVR | Cortical hypometabolic areas alongside subcortical regions (including the basal ganglia and thalamus) are early features of HIV-associated dementia (211, 213). | Moderate |
| 18 kDa (TSPO) | SUVR | There is a significant increase in expression in subcortical gray matter, particularly in the basal ganglia, including the globus pallidus, caudate nucleus, and putamen (214). | ||
| [11C]-(R)- PK11195 | SUVR | In HIV patients, there is a significant increase in [iC]-R-PK11195 binding in the thalamus, putamen, cerebellum, frontal cortex, and occipital cortex (217). | Moderate |
CSF, cerebrospinal fluid; CT, computed tomography; MRI, magnetic resonance imaging; DTI, diffusion tensor imaging; rsfMRI, resting-state fMRI; MRS, magnetic resonance spectroscopy; NAA, N-acetyl aspartate; Glu, Glutamic acid; Cho, Choline; MI, myoinositol; PET, positron emission tomography; SUVR, standardized uptake value ratios.