# Implications and prospects of immunological and neuroimaging research in HIV-associated neurocognitive disorders

**Authors:** Xing-Yuan Jiang, Chuan-Ke Hou, Ju-Ming Ma, Jiao-Jiao Liu, Wei Wang, Xire Aili, Qian-ru Wang, Fan Xu, Hai-Xia Luo, Yan-Bin Shi, Ling-Ling Zhao, Hong-Jun Li

PMC · DOI: 10.3389/fneur.2026.1699610 · 2026-02-20

## TL;DR

This paper reviews how combining neuroimaging and immunology can improve early detection and understanding of cognitive issues in HIV patients.

## Contribution

The paper highlights the novel integration of neuroimaging and immunological markers for diagnosing and understanding HIV-associated neurocognitive disorders.

## Key findings

- Combining neuroimaging with immunological markers improves early detection of HAND.
- Current diagnostic methods like the Frascati criteria have limitations in sensitivity and practicality.
- Emerging treatment strategies emphasize the importance of early detection for potential HIV eradication.

## Abstract

Combination antiretroviral therapy effectively controls viral replication in HIV-infected individuals, yet cognitive and motor impairments persist in 30–60% of patients, contributing to HIV-associated neurocognitive disorders (HAND). Current diagnostic approaches, such as the Frascati criteria, remain limited by practicality and sensitivity. Integrating neuroimaging with immunological markers may enhance early detection and mechanistic understanding.

We conducted a literature search in PubMed and Web of Science for articles published between 1990 and 2024, using keywords including “HIV-associated neurocognitive disorders,” “HIV,” “immunity,” “neuroimaging,” and “treatment.” Additional relevant publications were identified through manual review of reference lists.

This review synthesizes current epidemiology, diagnostic methods, and neuroimmune mechanisms underlying HAND. It summarizes available neuroimaging techniques and associated biomarkers, emphasizing progress in combining neuroimaging with immunology to identify structural and functional neural changes. Abnormal neuroimaging findings coupled with immunological markers show promise for earlier detection compared to cognitive assessments alone.

We highlight the systemic connections between early HAND diagnosis and the synergistic use of neuroimaging and immunology, identifying candidate biomarkers in HAND pathogenesis. Furthermore, we discuss emerging treatment strategies and the relevance of early detection in the context of potential HIV eradication.

## Full-text entities

- **Genes:** IL6R (interleukin 6 receptor) [NCBI Gene 3570] {aka CD126, HIES5, IL-1Ra, IL-6R, IL-6R-1, IL-6RA}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, IL33 (interleukin 33) [NCBI Gene 90865] {aka C9orf26, DVS27, IL1F11, NF-HEV, NFEHEV}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, CCL3 (C-C motif chemokine ligand 3) [NCBI Gene 6348] {aka G0S19-1, LD78, LD78ALPHA, MIP-1-alpha, MIP1A, SCI}, NEFL (neurofilament light chain) [NCBI Gene 4747] {aka CMT1F, CMT2E, CMTDIG, NF-L, NF68, NFL}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, C3AR1 (complement C3a receptor 1) [NCBI Gene 719] {aka AZ3B, C3AR, HNFAG09}, IRF8 (interferon regulatory factor 8) [NCBI Gene 3394] {aka H-ICSBP, ICSBP, ICSBP1, IMD32A, IMD32B, IRF-8}, CXCL9 (C-X-C motif chemokine ligand 9) [NCBI Gene 4283] {aka CMK, Humig, MIG, SCYB9, crg-10}, CFH (complement factor H) [NCBI Gene 3075] {aka AHUS1, AMBP1, ARMD4, ARMS1, CFHL3, FH}, NELFCD (negative elongation factor complex member C/D) [NCBI Gene 51497] {aka HSPC130, NELF-C, NELF-D, TH1, TH1L}, LGALS9 (galectin 9) [NCBI Gene 3965] {aka HUAT, LGALS9A}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IGF2 (insulin like growth factor 2) [NCBI Gene 3481] {aka C11orf43, GRDF, IGF-II, PP9974, SRS3}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, CD1E (CD1e molecule) [NCBI Gene 913] {aka R2}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, Nef [NCBI Gene 156110], STAT5A (signal transducer and activator of transcription 5A) [NCBI Gene 6776] {aka MGF, STAT5}, CXCR3 (C-X-C motif chemokine receptor 3) [NCBI Gene 2833] {aka CD182, CD183, CKR-L2, CMKAR3, GPR9, IP10-R}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, C1QA (complement C1q A chain) [NCBI Gene 712] {aka C1QD1}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, CD38 (CD38 molecule) [NCBI Gene 952] {aka ADPRC 1, ADPRC1, cADPR1}, MBL2 (mannose binding lectin 2) [NCBI Gene 4153] {aka COLEC1, HSMBPC, MBL, MBL2D, MBP, MBP-C}, ERVK-6 (endogenous retrovirus group K member 6, envelope) [NCBI Gene 64006] {aka ERVK6, HERV-K(C7), HERV-K108, K-Rev, c-orf, cORF}, C5AR2 (complement C5a receptor 2) [NCBI Gene 27202] {aka C5L2, GPF77, GPR77}, C3 (complement C3) [NCBI Gene 718] {aka AHUS5, ARMD9, ASP, C3a, C3b, CPAMD1}, PLK1 (polo like kinase 1) [NCBI Gene 5347] {aka PLK, STPK13}, PRNP (prion protein (Kanno blood group)) [NCBI Gene 5621] {aka ASCR, AltPrP, CD230, CJD, GSS, KURU}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, CSF3 (colony stimulating factor 3) [NCBI Gene 1440] {aka C17orf33, CSF3OS, GCSF}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CCL13 (C-C motif chemokine ligand 13) [NCBI Gene 6357] {aka CKb10, MCP-4, NCC-1, NCC1, SCYA13, SCYL1}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, C1QB (complement C1q B chain) [NCBI Gene 713] {aka C1QD2}, S100B (S100 calcium binding protein B) [NCBI Gene 6285] {aka NEF, S100, S100-B, S100beta}, NEFH (neurofilament heavy chain) [NCBI Gene 4744] {aka CMT2CC, NFH}, CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 6387] {aka IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1}, IL9 (interleukin 9) [NCBI Gene 3578] {aka HP40, IL-9, P40}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, FGF1 (fibroblast growth factor 1) [NCBI Gene 2246] {aka AFGF, ECGF, ECGF-beta, ECGFA, ECGFB, FGF-1}, CX3CR1 (C-X3-C motif chemokine receptor 1) [NCBI Gene 1524] {aka CCRL1, CMKBRL1, CMKDR1, GPR13, GPRV28, V28}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, MAP2 (microtubule associated protein 2) [NCBI Gene 4133] {aka MAP-2, MAP2A, MAP2B, MAP2C}, TREM2 (triggering receptor expressed on myeloid cells 2) [NCBI Gene 54209] {aka AD17, PLOSL2, TREM-2, Trem2a, Trem2b, Trem2c}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CCL4 (C-C motif chemokine ligand 4) [NCBI Gene 6351] {aka ACT2, AT744.1, G-26, HC21, LAG-1, LAG1}, GJA1 (gap junction protein alpha 1) [NCBI Gene 2697] {aka AVSD3, CMDR, CX43, EKVP, EKVP3, GJAL}, TSPO (translocator protein) [NCBI Gene 706] {aka BPBS, BZRP, DBI, IBP, MBR, PBR}, NECTIN1 (nectin cell adhesion molecule 1) [NCBI Gene 5818] {aka CD111, CLPED1, ED4, HIgR, HV1S, HVEC}, HMGB1 (high mobility group box 1) [NCBI Gene 3146] {aka HMG-1, HMG1, HMG3, SBP-1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852] {aka CD184, D2S201E, FB22, HM89, HSY3RR, LCR1}, ADAM10 (ADAM metallopeptidase domain 10) [NCBI Gene 102] {aka AD10, AD18, CD156c, CDw156, HsT18717, MADM}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, CSF1R (colony stimulating factor 1 receptor) [NCBI Gene 1436] {aka BANDDOS, C-FMS, CD115, CSF-1R, CSFR, FIM2}
- **Diseases:** HANDs (MESH:D006230), anxiety disorders (MESH:D001008), damage (MESH:D020263), HAD (MESH:D016263), frailty (MESH:D000073496), GM atrophy (MESH:D002549), neurocognitive deficits (MESH:D009461), specific (MESH:D000080888), kidney function decline (MESH:D007680), viremia (MESH:D014766), impairments in memory (learning (MESH:D007859), motor slowing (MESH:D012897), compromised white matter (MESH:D056784), AIDS-related diseases (MESH:D000163), obesity (MESH:D009765), Smoking (MESH:D015208), immune reconstitution inflammatory syndrome (MESH:D054019), atrophy (MESH:D001284), cannabis use disorder (MESH:D002189), neuroinflammation (MESH:D000090862), CNS damage (MESH:D002493), neurotoxic (MESH:D020258), neural abnormalities (MESH:D015441), insomnia (MESH:D007319), substance abuse (MESH:D019966), brain atrophy (MESH:C566985), behavioral abnormalities (MESH:D001523), AD (MESH:D000544), cognitive abnormalities (MESH:D060825), opportunistic infections (MESH:D009894), diabetes (MESH:D003920), sleep disorders (MESH:D012893), mitochondrial toxicity (MESH:D028361), and central nervous system inflammation (MESH:D007249), shock (MESH:D012769), neurodegeneration (MESH:D019636), neural injury (MESH:D014947), volume loss (MESH:D016388), axonal damage (MESH:D001480), tissue damage (MESH:D017695), dopaminergic system dysfunction (MESH:D009422), cognitive and motor impairments (MESH:D003072), infectious (MESH:D003141), attention/working memory impairments (MESH:D008569), FA (MESH:D054144), chronic (MESH:D002908), ANI (MESH:D058070), immune dysregulation (OMIM:614878), HIV disease (MESH:D015658), synaptic dysfunction (MESH:C536122), DTI (MESH:C564543), bipolar disorders (MESH:D001714), chRMs (MESH:C562377), cortical dysfunction (MESH:D054220), associated (MESH:D018886), dementia (MESH:D003704), amyloid (MESH:C000718787), MD (MESH:D008228), sleep fragmentation (MESH:D012892), obstructive sleep apnea (MESH:D020181)
- **Chemicals:** Neopterin (MESH:D019798), GABA (MESH:D005680), Maraviroc (MESH:D000077592), GLU (MESH:D018698), H2O (MESH:D014867), efavirenz (MESH:C098320), Cho (MESH:D002794), MI (MESH:D007294), glucose (MESH:D005947), reactive oxygen species (MESH:D017382), calcium (MESH:D002118), dopamine (MESH:D004298), H (MESH:D006859), Alcohol (MESH:D000438), lipid (MESH:D008055), Gln (MESH:D005973), 18F-FDG (MESH:D019788), nicotine (MESH:D009538), Creatine (MESH:D003401), Cr (MESH:D002857), N-Acetylaspartate (MESH:C000179), Tc-HMPAO (MESH:D019690), [11C]-PK11195 (MESH:C504060), CA (-), methamphetamine (MESH:D008694)
- **Species:** Macaca nemestrina (pig-tailed macaque, species) [taxon 9545], Human immunodeficiency virus 1 (no rank) [taxon 11676], Qubevirus faecium (species) [taxon 39804], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Macaca mulatta (rhesus macaque, species) [taxon 9544], Human immunodeficiency virus (species) [taxon 12721]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12965621/full.md

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Source: https://tomesphere.com/paper/PMC12965621