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Viruses
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Neurocognitive Dynamics and Biomarkers in HIV
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Neurocognitive Dynamics and Biomarkers in HIV

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 1 November 2025 | Viewed by 587

Special Issue Editors

Dr. Mattia Trunfio

E-Mail Website
Guest Editor
Center for AIDS Research (CFAR), Division of Infectious Diseases and Global Health, University of California, San Diego, CA, USA
Interests: neuroHIV; CSF biomarkers; cognitive disorders; central nervous system infections; CNS virome; neuroinflammation; HIV reservoir
Dr. Carmela Pinnetti

E-Mail Website
Guest Editor
HIV/AIDS Unit, Clinical Department, National Institute for Infectious Disease "L. Spallanzani", Rome, Italy
Interests: neuroHIV; HIV-associated neurocognitive disorders; HIV-associated dementia; clinical pharmacology of antiretrovirals; neurotoxicity; CSF viral escape

Special Issue Information

Dear Colleagues,

HIV infection, both in and outside the central nervous system (CNS), can lead to significant neuroinflammation, which is intricately linked to various clinical consequences, including mood disorders, cognitive decline, and neurodegeneration. The mechanisms underlying these effects are complex and multifaceted, involving factors such as aging, comorbidities, co-infections, pharmacological contributions, substance use disorders, systemic inflammation, and HIV persistence in the CNS. As we navigate this landscape, innovative techniques are emerging, e.g., ultrasensitive assays for molecular biomarkers, proteomics, transcriptomics, and advanced imaging methods. New approaches for analyzing the complexity and granularity of the data generated by these techniques are also expanding, such as advanced clustering methods and AI-integrated machine learning.

This Special Issue will focus on the diagnostic and prognostic value of biomarkers of any type—such as molecular, genetic/epigenetic, imaging, and microbial—in relation to the brain and mental health of people living with HIV. It will encompass original research, reviews, and case studies that highlight the latest findings in this field. Our goal is to illuminate the complex interplay between HIV infection and persistence, neuroinflammation, and neurocognitive dysfunction while fostering interdisciplinary approaches that integrate clinical insights with cutting-edge research. By bringing together diverse perspectives, we aim to enhance our understanding of these critical issues and inform the development of targeted interventions that improve outcomes for those living with HIV. We invite contributions to advance our collective knowledge and stimulate further research in this important area.

Dr. Mattia Trunfio
Dr. Carmela Pinnetti
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • HIV infection
  • neurodegeneration
  • biomarkers
  • neuroinflammation
  • cognitive performance
  • mood
  • central nervous system

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Published Papers (2 papers)

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Research

15 pages, 752 KiB  
Article
Relationship Between Estimated Drug Distribution of Antiretroviral Therapy and Immune Proteins in Cerebrospinal Fluid During Chronic HIV Suppression
by Mattia Trunfio, Jennifer E. Iudicello, Patricia K. Riggs, Asha R. Kallianpur, Todd Hulgan, Ronald J. Ellis and Scott L. Letendre
Viruses 2025, 17(6), 749; https://doi.org/10.3390/v17060749 - 23 May 2025
Abstract
Antiretroviral therapy (ART) drugs vary in their distribution into cerebrospinal fluid (CSF), which can be estimated using the central nervous system (CNS) penetration effectiveness (CPE) score. Although higher CPE has been associated with lower CSF HIV RNA levels, its relationship to CSF inflammation [...] Read more.
Antiretroviral therapy (ART) drugs vary in their distribution into cerebrospinal fluid (CSF), which can be estimated using the central nervous system (CNS) penetration effectiveness (CPE) score. Although higher CPE has been associated with lower CSF HIV RNA levels, its relationship to CSF inflammation is less clear. We investigated associations between CPE and three CSF immune biomarkers (CXCL10, TNF-α, and IL-6) in 275 virally suppressed people with HIV (PWH) on three-drug ART regimens using a training–validation design. Participants were randomized into training (TG, n = 144) and validation (VG, n = 131) groups with similar demographics, ART characteristics, and CPE scores. The CSF levels of the biomarkers were quantified by bead suspension array-based immunoassays. In both groups, higher CPE correlated with lower levels of CXCL10 (TG: r = −0.31, p < 0.001; VG: r = −0.30, p < 0.001) and TNF-α (TG: r = −0.19, p = 0.04; VG: r = −0.18, p = 0.03), with remarkably similar effect size. CPE did not correlate with IL-6 in either group. Multivariable models confirmed the associations between higher CPE and both lower CXCL10 (R2 = 0.16, p < 0.001) and TNF-α (R2 = 0.07, p = 0.02) in CSF, and supported the relative resistance of IL-6 to ART effects. During suppressive ART, regimens that achieve higher concentrations in the CNS may better reduce some indicators of CSF inflammation (CXCL10 and TNF-α, closely related to the interferon pathway), but they may not fully normalize the neuroimmune environment (IL-6). Distinct ART regimens may produce different neuroimmune signatures, potentially contributing to heterogeneous patterns of brain injury. Full article
(This article belongs to the Special Issue Neurocognitive Dynamics and Biomarkers in HIV)
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13 pages, 528 KiB  
Article
Implications of Cognitive Impairment on Antihypertensive Medication Use in HIV
by Azin Tavasoli, Bin Tang, Mohammadsobhan S. Andalibi, Donald R. Franklin, Scott L. Letendre, Robert K. Heaton and Ronald J. Ellis
Viruses 2025, 17(4), 470; https://doi.org/10.3390/v17040470 - 26 Mar 2025
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Abstract
Background: Aging-related comorbidities such as cardiovascular disease and neurocognitive impairment are more common among people with HIV (PWH). Hypertension (HTN) has been implicated in cognitive decline, and antihypertensives with anticholinergic properties may exacerbate this decline. Our research probed the relationship between neurocognitive performance [...] Read more.
Background: Aging-related comorbidities such as cardiovascular disease and neurocognitive impairment are more common among people with HIV (PWH). Hypertension (HTN) has been implicated in cognitive decline, and antihypertensives with anticholinergic properties may exacerbate this decline. Our research probed the relationship between neurocognitive performance and antihypertensives in hypertensive PWH and in those without HIV (PWoH), examining whether increased antihypertensives followed the worsening in neurocognitive performance. Methods: This longitudinal analysis encompassed seven visits over five years, enrolled between 1999 and 2022. Participants were included if they reported HTN or used antihypertensives. All participants underwent comprehensive cognitive assessments, and their global cognitive performance was evaluated using summary, demographically corrected T-scores. The association between the global T-score and the number of antihypertensives was evaluated using generalized linear mixed-effects models. Summary regression-based change score (sRCS) was analyzed as an indicator of global performance over time. Results: Among 1158 hypertensive PWH (79.9% were on ART), worsening cognitive performance was associated with an increased number of antihypertensives (p = 0.012) but not in PWoH (p = 0.58). PWH had lower mean arterial pressure (MAP) than PWoH after adjusting for demographics (β = −5.05, p = 2.3 × 10−11). In PWH, an association between mean arterial pressure (MAP) and sRCS suggested that those with cognitive improvement had lower MAP (p = 0.027). PWH taking more anticholinergics were more likely to have worse cognitive performance over time (p < 0.001). Conclusions: PWH with declining neurocognitive performance over time used increasing numbers of antihypertensives, suggesting that their providers prescribed more antihypertensives because of either treatment refractory HTN or poor adherence. Prescribers should avoid using antihypertensives with anticholinergic properties when possible. Full article
(This article belongs to the Special Issue Neurocognitive Dynamics and Biomarkers in HIV)
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