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Microorganisms
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HIV Infections: Comorbidities, Clinical Challenges, and Antiretroviral Advances
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HIV Infections: Comorbidities, Clinical Challenges, and Antiretroviral Advances

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Virology".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 3332

Special Issue Editors

Dr. José Ramón Blanco

E-Mail Website
Guest Editor
Infectious Diseases Department, San Pedro University Hospital-Center for Biomedical Research from La Rioja (CIBIR), 26006 Logroño, Spain
Interests: aging; circadian rhythm; COVID-19; emerging infection; inflammaging; HIV-infection; senolytics; senescence; virus infection
Special Issues, Collections and Topics in MDPI journals
Dr. Enrique Bernal-Morell

E-Mail Website
Guest Editor
Unit of Infectious Diseases, Hospital General Universitario Reina Sofía, Universidad de Murcia, 30003 Murcia, Spain
Interests: Infectious Diseases; biomarkers

Special Issue Information

Dear Colleagues,

HIV care has moved beyond achieving an undetectable viral load to the lifelong management of multimorbidity. As people living with HIV age, cardiometabolic disease, neurocognitive impairment, malignancies, mental health conditions, and frailty increasingly shape clinical outcomes. These comorbidities intersect with antiretroviral therapy through chronic inflammation, polypharmacy, drug–drug interactions, and adherence constraints, revealing gaps in screening, risk stratification, and models of care. This Special Issue centers on the interface between comorbidities and ART, and the practical challenges clinicians face across diverse settings.

We invite submissions that characterize comorbidity phenotypes and trajectories, quantify excess risks, and evaluate preventive and therapeutic strategies, including long-acting regimens, treatment simplification, and regimen switching, while also addressing implementation barriers and health inequities.

Eligible contributions include randomized and pragmatic trials, cohort and registry analyses, real-world evidence, translational studies on biomarkers and immune activation, pharmacology and interaction studies, decision-analytic modeling, and qualitative research centered on patient experience. Work focusing on priority populations (older adults, women, and migrants), coinfections (HBV/HCV and tuberculosis), and topics such as low-level viraemia, resistance, or integrated care pathways is encouraged.

Dr. José Ramón Blanco
Dr. Enrique Bernal-Morell
Guest Editors

Manuscript Submission Information

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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. Microorganisms 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 2700 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
  • HIV multimorbidity
  • antiretroviral therapy
  • coinfections
  • viraemia

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Published Papers (5 papers)

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14 pages, 942 KB  
Article
Humoral Immunogenicity of SARS-CoV-2 mRNA Primary Vaccination Among People with HIV
by Daniel K. Nomah, Alba G. Robles, Andreu Bruguera, Juan M. Tiraboschi, Susana Benet, Javier García-Pérez, Paloma Jimenez, Ingrid Vilaró, Gemma Navarro, Sonsoles Sánchez-Palomino, Paula Suanzes, Mercedes Garcia-Gasalla, Francisco Homar, Beatriz Mothe, Jordi Casabona, Juliana Reyes-Urueña, María J. Buzón, Jose M. Miro and The COVIHVAC Study Group
Microorganisms 2026, 14(4), 893; https://doi.org/10.3390/microorganisms14040893 - 16 Apr 2026
Viewed by 242
Abstract
People with HIV (PWH) may exhibit altered immune responses to SARS-CoV-2 vaccination due to persistent immune dysregulation despite antiretroviral therapy. We evaluated humoral immunogenicity following mRNA SARS-CoV-2 vaccination in PWH according to CD4 T-cell count and compared responses with HIV-negative controls. The study [...] Read more.
People with HIV (PWH) may exhibit altered immune responses to SARS-CoV-2 vaccination due to persistent immune dysregulation despite antiretroviral therapy. We evaluated humoral immunogenicity following mRNA SARS-CoV-2 vaccination in PWH according to CD4 T-cell count and compared responses with HIV-negative controls. The study included 57 PWH stratified by CD4 count (<200 and ≥200 cells/µL), alongside 12 HIV-negative controls. Neutralizing antibody titers (NT50) against SARS-CoV-2 pseudoviruses expressing the D614G and Omicron BA.5 spike variants were measured using a luciferase-based neutralization assay one month (M1) and six months (M6) after primary vaccination with BNT162b2 or mRNA-1273. PWH with CD4 counts ≥ 200 cells/µL demonstrated higher neutralizing titers against D614G at M1 and M6, with significant differences observed between CD4 groups (M1: p = 0.03; M6: p = 0.02). Neutralization of BA.5 was lower overall; while no overall group differences were observed at M1, higher titers were detected among individuals with CD4 ≥ 200 cells/µL at six months (p = 0.04). Neutralizing titers correlated positively with CD4 counts among PWH. Responses were broadly comparable between PWH and HIV-negative controls and did not differ substantially by vaccine type. These findings indicate that immune status, reflected by CD4 T-cell count, is a key determinant of SARS-CoV-2 vaccine-induced humoral responses in PWH and support prioritizing vaccination strategies for individuals with advanced immunosuppression. Full article
(This article belongs to the Special Issue HIV Infections: Comorbidities, Clinical Challenges, and Antiretroviral Advances)
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11 pages, 750 KB  
Article
Optimizing Salvage ART: Real-World Outcomes of Doravirine Plus DTG or BIC in Heavily Treatment-Experienced Persons Living with HIV
by Irina Ianache, Roxana Radoi, Gratiela Tardei, Mike Youle and Cristiana Oprea
Microorganisms 2026, 14(2), 390; https://doi.org/10.3390/microorganisms14020390 - 6 Feb 2026
Viewed by 534
Abstract
Management of heavily treatment-experienced people living with HIV (HTE-PWH) remains challenging due to long antiretroviral therapy (ART) exposure and limited treatment options. We conducted an observational, real-world-data study on HTE-PWH in active care at the “Victor Babeș” Hospital, Bucharest, receiving doravirine (DOR)-based salvage [...] Read more.
Management of heavily treatment-experienced people living with HIV (HTE-PWH) remains challenging due to long antiretroviral therapy (ART) exposure and limited treatment options. We conducted an observational, real-world-data study on HTE-PWH in active care at the “Victor Babeș” Hospital, Bucharest, receiving doravirine (DOR)-based salvage regimens combined with dolutegravir (DTG) or bictegravir (BIC). Epidemiological, clinical, and laboratory variables were analyzed according to HIV acquisition mode and salvage regimen. Sixty-nine PWH were included; 57.9% male, with a median age of 36 years. Median ART duration before switch was 21.5 years. HIV was acquired parenterally in childhood (PM) in 64.7% cases. Salvage regimens included BIC/FTC/TAF + DOR (50.0%), 3TC/TDF/DOR + DTG (35.2%), and 3TC/DTG + DOR (14.7%). The median nadir CD4 count was 37 cells/µL, and the median viral load at diagnosis was 5.24 log10 copies/mL. Switching was performed for regimen simplification (n = 32) or non-adherence-related virological failure (n = 37). At switch, 53.6% had detectable viremia. Viral suppression was achieved in 68.3% at 6 months and 75.0% at 12 months. Individuals with PM infection were younger and had longer ART exposure than those with heterosexual acquisition. DOR-based salvage regimens combined with DTG or BIC were effective in adherent HTE-PWH, particularly those with extensive ART histories. Full article
(This article belongs to the Special Issue HIV Infections: Comorbidities, Clinical Challenges, and Antiretroviral Advances)
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15 pages, 1667 KB  
Article
Maladaptive Trained Immunity Drives Persistent IL-6 Production and Enhanced TLR Responsiveness in Monocyte-Derived Macrophages from People Living with HIV
by Larisa Dubrovsky, Tatiana Pushkarsky, Beda Brichacek, Ashley Bastin, Afsoon Roberts, Jose Lucar, Maria Elena Ruiz, Oleksandr Semeniuk, Marc Siegel, Dmitri Sviridov and Michael I. Bukrinsky
Microorganisms 2026, 14(2), 355; https://doi.org/10.3390/microorganisms14020355 - 3 Feb 2026
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Abstract
Trained immunity (TRIM) enhances innate immune responses through epigenetic and metabolic reprogramming but may become maladaptive, contributing to chronic inflammation. In people living with HIV (PLWH), maladaptive TRIM has been proposed but remains insufficiently characterized. We examined inflammatory cytokine production in monocyte-derived macrophages [...] Read more.
Trained immunity (TRIM) enhances innate immune responses through epigenetic and metabolic reprogramming but may become maladaptive, contributing to chronic inflammation. In people living with HIV (PLWH), maladaptive TRIM has been proposed but remains insufficiently characterized. We examined inflammatory cytokine production in monocyte-derived macrophages (MDMs) obtained from PLWH and age-matched individuals without HIV infection. Baseline cytokine output and responses to stimulation of Toll-like receptors (TLR) were measured. We further examined whether TRIM influenced susceptibility to HIV infection in MDMs derived from monocytes exposed to extracellular vesicles carrying the HIV-1 Nef protein (Nef EVs). Baseline IL-6 production did not differ between unstimulated MDMs from PLWH and uninfected controls. Although sex-associated differences were initially observed, these effects were no longer significant after adjustment for infection duration. IL-6 responses following TLR2 and TLR7 stimulation, but not TLR4 stimulation, were significantly amplified in PLWH-derived MDMs, consistent with a trained phenotype. Similar trends were observed in sex-stratified analyses but did not reach statistical significance. The magnitude of unstimulated IL-6 production positively correlated with duration of HIV infection, suggesting cumulative TRIM imprinting over time. Despite heightened inflammatory responsiveness, TRIM did not reduce susceptibility to HIV infection in Nef EV-exposed MDMs, indicating functional maladaptation rather than protective priming. These findings provide evidence of maladaptive TRIM in PLWH, characterized by preserved basal cytokine output but exaggerated inflammatory responses to innate immune stimulation without antiviral benefit. The association with infection duration supports progressive innate immune reprogramming as a contributor to HIV-associated inflammation. No statistically significant differences in trained immune responses were observed between male and female PLWH after accounting for duration of infection. Further studies are needed to define the mechanisms underlying this maladaptation and its clinical consequences. Full article
(This article belongs to the Special Issue HIV Infections: Comorbidities, Clinical Challenges, and Antiretroviral Advances)
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13 pages, 495 KB  
Article
Impact of Switching from Oral to Long-Acting Injectable Cabotegravir and Rilpivirine on the Lipid Profile of HIV-Positive Patients
by Marta Segura Díaz, Antonio Collado Romacho and Sergio Ferra Murcia
Microorganisms 2026, 14(1), 22; https://doi.org/10.3390/microorganisms14010022 - 21 Dec 2025
Viewed by 579
Abstract
Long-acting cabotegravir and rilpivirine (LA-CAB/RPV) have been incorporated into the treatment of people living with HIV (PLWH), but evidence on their metabolic impact in real-world settings remains limited. This retrospective study analyzed the lipid profiles of 39 PLWH who switched from daily oral [...] Read more.
Long-acting cabotegravir and rilpivirine (LA-CAB/RPV) have been incorporated into the treatment of people living with HIV (PLWH), but evidence on their metabolic impact in real-world settings remains limited. This retrospective study analyzed the lipid profiles of 39 PLWH who switched from daily oral antiretroviral therapy to LA-CAB/RPV. Lipid parameters were compared before and seven months after the switch. No significant differences were observed in total cholesterol, LDL cholesterol, or triglycerides, indicating that LA-CAB/RPV did not worsen the lipid profile. However, HDL cholesterol increased significantly from 49.4 ± 11.5 mg/dL to 53.0 ± 11.9 mg/dL (p = 0.0065). Viral suppression and CD4 counts remained stable throughout the study period. These findings suggest that switching to long-acting injectable cabotegravir and rilpivirine maintains virological and immunological control without adversely affecting the total cholesterol, LDL cholesterol, or triglycerides, and is associated with an improvement in HDL cholesterol. LA-CAB/RPV therefore appears to be a metabolically safe therapeutic option for PLWH, with a potentially favorable effect on cardiovascular risk factors. Full article
(This article belongs to the Special Issue HIV Infections: Comorbidities, Clinical Challenges, and Antiretroviral Advances)
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15 pages, 39559 KB  
Systematic Review
Prevalence of Fungemia in People with HIV: A Systematic Review and Meta-Analysis
by Asta Maria Blom Nielsen, Kristiana Alexandrova Nikolova, Tea Nynne Sanders, Ask Bock, Moises Alberto Suarez-Zdunek and Susanne Dam Nielsen
Microorganisms 2026, 14(1), 225; https://doi.org/10.3390/microorganisms14010225 - 19 Jan 2026
Viewed by 679
Abstract
Prior to the introduction of antiretroviral therapy (ART), people with HIV (PWH) had high risk of fungemia. No systematic review has assessed the prevalence of fungemia in PWH after the introduction of combination ART in 1996. The primary objective of this systematic review [...] Read more.
Prior to the introduction of antiretroviral therapy (ART), people with HIV (PWH) had high risk of fungemia. No systematic review has assessed the prevalence of fungemia in PWH after the introduction of combination ART in 1996. The primary objective of this systematic review was to determine the prevalence of fungemia in adult PWH after 1996. Furthermore, we aimed to compare the prevalence of fungemia in different ART time periods to determine geographic differences and fungal pathogen distribution. A systematic literature search was performed on 7 March 2025 across six databases and the study quality was assessed using the Newcastle–Ottawa scale. Prevalence estimates were extracted, and a meta-analysis was performed using a random effects model. Twelve studies comprising 27,729 PWH were included. The overall pooled prevalence in PWH was 3.3% (95% CI: 1.53; 4.96%, I2 = 98.9%). The most common pathogen to cause fungemia was Talaromyces marneffei with a prevalence of 4.8%, although this pathogen was limited to studies from Asia. The highest prevalence of fungemia in PWH was 6.8% in Asia. The prevalence of fungemia was 5.8% between July 1996–September 2015 and 1.0% between September 2015–January 2025, but the difference was not statistically significant (p = 0.273). However, all findings were limited by very low certainty of evidence and should be interpreted with caution. In conclusion, our findings suggest that fungemia persists among PWH despite ART, especially in Asia. Given the limited available evidence, it was not possible to determine whether the prevalence of fungemia changed following the change in ART treatment guidelines in September 2015. The protocol is registered in PROSPERO (CRD420251005081). Full article
(This article belongs to the Special Issue HIV Infections: Comorbidities, Clinical Challenges, and Antiretroviral Advances)
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