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19 pages, 1019 KB  
Article
Oral Lesions in People Living with HIV: The Lining HIV Study
by Maria Gavatha, Emmanouil Angelos Rigopoulos, Miranda Alexopoulou, Vasileios Petrakis, Nikoleta Babaka, Olga Tsachouridou, Dimitrios Pilalas, Charis Chari, Alexandra Vorria, Evaggelia Bogosian, Petros Ioannou, Sofia Ioannou, Efstratios Patsatzis, Maria N. Gamaletsou, Andreas Rafail Tzatzimos, Periklis Panagopoulos, Symeon Metallidis, Dimitrios Papazoglou, Konstantinos Tosios and Karolina Akinosoglou
Pathogens 2026, 15(7), 679; https://doi.org/10.3390/pathogens15070679 (registering DOI) - 26 Jun 2026
Abstract
Oral manifestations are common in people living with HIV (PLWH) and may affect oral health-related quality of life (OHRQoL), while data from Greece remain limited. This multicenter prospective cohort study evaluated oral health status and OHRQoL among PLWH and explored associations with antiretroviral [...] Read more.
Oral manifestations are common in people living with HIV (PLWH) and may affect oral health-related quality of life (OHRQoL), while data from Greece remain limited. This multicenter prospective cohort study evaluated oral health status and OHRQoL among PLWH and explored associations with antiretroviral therapy (ART) and clinical factors. Overall, 370 PLWH from seven referral centers were included. Participants underwent oral examination, with oral hygiene assessed using the Simplified Oral Hygiene Index (OHI-S), and completed the Oral Health Impact Profile-14 (OHIP-14). Statistical analyses were performed using IBM SPSS Statistics v29.0, while multinomial and binary logistic regression identified predictors of oral hygiene status and OHRQoL, respectively. Most participants were male (76.5%), had CD4 counts ≥ 200 cells/μL (95.4%), and were receiving ART (98.6%). Annual dental check-ups, daily tooth brushing, mouthwash use, and dental floss use were reported by 54.1%, 69.5%, 31.9%, and 23.8%, respectively. The median OHI-S score was 2.0 (IQR:1.5–2.7), with 16.9% having poor OHI-S; the median OHIP-14 score was 11 (IQR: 7–15), with 64.4% reporting poor OHRQoL. Male sex was associated with lower odds of poor OHRQoL (OR = 0.377; p = 0.006), whereas ART regimen independently predicted poor OHRQoL. These findings support patient-centered oral healthcare within HIV care. Full article
20 pages, 302 KB  
Article
Magnitude and Factors Associated with HIV Viral Suppression Among Adult People Living with HIV-HBV Co-Infection in Northwest Ethiopia
by Mequanente Dagnaw, Destaw Fetene Teshome, Tilahun Bizuayehu Demass and Abebaw Gebyehu Worku
Trop. Med. Infect. Dis. 2026, 11(7), 175; https://doi.org/10.3390/tropicalmed11070175 - 26 Jun 2026
Abstract
Background: HIV-HBV co-infection remains a major public health challenge, particularly in sub-Saharan Africa. HBV co-infection worsens clinical outcomes among people living with HIV by accelerating liver disease and complicating treatment. Although antiretroviral therapy can effectively suppress both viruses, achieving optimal HIV viral suppression [...] Read more.
Background: HIV-HBV co-infection remains a major public health challenge, particularly in sub-Saharan Africa. HBV co-infection worsens clinical outcomes among people living with HIV by accelerating liver disease and complicating treatment. Although antiretroviral therapy can effectively suppress both viruses, achieving optimal HIV viral suppression remains critical for reducing morbidity and transmission. While several factors influencing viral suppression among PLHIV are well documented, evidence on HIV viral suppression among HIV-HBV co-infected individuals is limited, especially in resource-limited settings like Ethiopia. Furthermore, data on the magnitude of viral suppression and its associated factors in this population are scarce. Therefore, this study aimed to assess the magnitude of HIV viral suppression and identify its associated factors among adult HIV-HBV co-infected patients in Northwest Ethiopia. Objective: This study aimed to assess the magnitude and factors associated with HIV viral suppression among adult people living with HIV-HBV Co-infection in Northwest Ethiopia. Methods: An institution-based cross-sectional study was conducted in Northwest Ethiopia among adults with HIV-HBV co-infection on antiretroviral therapy. A simple random sample of 402 participants was selected. Data were collected using a pretested structured interviewer-administered questionnaire and medical record review, covering sociodemographic, clinical, behavioral, treatment, follow-up, and adherence factors. HIV viral suppression was defined as a plasma viral load < 1000 copies/mL. Data were coded in EpiData 4.6 and analyzed using STATA 18. Descriptive statistics estimated suppression rates. Bivariable and multivariable logistic regression identified factors associated with suppression; variables with p < 0.25 in bivariable analysis were included in the multivariable model. Statistical significance was set at p < 0.05 with adjusted odds ratios and 95% confidence intervals reported. Model fit was assessed using the Hosmer–Lemeshow test, and multicollinearity was checked using variance inflation factors. Results: There were 423 participants in all. Among the 423 HIV-HBV co-infected adults on antiretroviral therapy included in this study, 138 (34, CI, 30–39%) achieved HIV viral suppression, while 264 (66%) had an unsuppressed viral load at the time of assessment. Viral suppression was found to be independently correlated with the ART TDF-3TC-LPV/r regimen, first-line medication adherence, bedridden functional level, missed clinic appointments, and length of therapy. While TDF-3TC-LPV/r usage (AOR 2.34; 95% CI: 1.40–3.90) and longer treatment duration (AOR 2.09; 95% CI: 1.30–3.34) were advantageous, good adherence significantly improved the likelihood of suppression (AOR 5.54; 95% CI: 3.27–9.38). Missed appointments and a bedridden state decreased the likelihood of suppression. Conclusions: HIV viral suppression was achieved in only 34% of participants. Adherence, ART regimen, treatment duration, functional status, and retention in care were significant predictors. Strengthening adherence support, patient retention, optimized ART regimens, routine viral load monitoring, and targeted care for high-risk patients could improve treatment outcomes and help Ethiopia achieve UNAIDS viral suppression targets. Full article
(This article belongs to the Special Issue HIV Testing, Prevention and Care Interventions, 2nd Edition)
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16 pages, 3631 KB  
Review
Efficacy and Safety of a Single Dose Versus Three Weekly Doses of Benzathine Penicillin G for Early Syphilis: A Systematic Review and Meta-Analysis
by Thanyarat Phumthian, Sudapree Sorasuchart and Samadhi Patamatamkul
Int. J. Transl. Med. 2026, 6(3), 26; https://doi.org/10.3390/ijtm6030026 - 26 Jun 2026
Abstract
Background/Objectives: To compare the efficacy and safety of a single dose versus three weekly doses of benzathine penicillin G (BPG) for the treatment of early syphilis. Methods: We searched Embase, PubMed, and Scopus for randomized controlled trials (RCTs) and prospective comparative [...] Read more.
Background/Objectives: To compare the efficacy and safety of a single dose versus three weekly doses of benzathine penicillin G (BPG) for the treatment of early syphilis. Methods: We searched Embase, PubMed, and Scopus for randomized controlled trials (RCTs) and prospective comparative studies published in English up to September 2025. The primary outcome was serological cure (≥4-fold decline in non-treponemal titers) at 6–12 months, analyzed on an intention-to-treat (ITT) basis. Risk of bias was assessed using RoB 2 for RCTs and ROBINS-I for non-randomized studies; certainty of evidence was rated with GRADE. Data were synthesized using random-effects meta-analysis and trial sequential analysis (TSA). Results: Three studies (n = 886) met the inclusion criteria. The primary ITT meta-analysis showed no significant difference in serological cure between the three-dose and single-dose regimens (risk ratio [RR] 1.06; 95% CI 0.92–1.21; p = 0.42), with substantial heterogeneity. In an exploratory pre-specified subgroup of patients with high baseline RPR (≥1:32), the three-dose regimen was associated with higher cure rates (RR 1.12; 95% CI 1.02–1.23; p = 0.02; I2 = 0%), but no significant benefit was seen for people with HIV (PWH) (RR 1.08; p = 0.13) or for those with CD4 counts <350 cells/mm3. Risk of bias was serious across all studies, and GRADE certainty was very low for efficacy and low for safety. In a post hoc per-protocol analysis restricted to early latent syphilis, the three-dose regimen yielded higher serological cure (pooled risk difference 12%, 95% CI 1–23; p = 0.03). TSA indicated that the evidence is inconclusive and underpowered. Conclusions: On the basis of the ITT analysis, a single dose of BPG appears to remain effective and safe for most cases of early syphilis, including in PWH, supporting current CDC and WHO recommendations. The apparent advantages of three doses in high-titer and early latent subgroups derive from exploratory and post hoc analyses of studies at high risk of bias with very low certainty of evidence and should be regarded as hypothesis-generating rather than practice-changing. Adequately powered, well-designed trials are needed before any dose stratification can be recommended. Full article
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18 pages, 1163 KB  
Article
Distinct Patterns of Clinical Features and Cardiac Biomarker Elevation in Community-Acquired Pneumonia and COVID-19 Pneumonia
by Murimisi Mukansi, Helen C. Steel, Theresa M. Rossouw, Ismail Kalla, Colin Menezes, Martin Nieuwoudt, Ronald Anderson and Charles Feldman
Pathogens 2026, 15(7), 676; https://doi.org/10.3390/pathogens15070676 - 26 Jun 2026
Abstract
No previous sub-Saharan studies have compared patients with community-acquired pneumonia (CAP) and COVID-19 pneumonia, the focus of this study. Consecutive adult patients hospitalized with CAP (n = 59) or COVID-19 pneumonia (n = 74) were compared regarding multiple characteristics, including cardiac [...] Read more.
No previous sub-Saharan studies have compared patients with community-acquired pneumonia (CAP) and COVID-19 pneumonia, the focus of this study. Consecutive adult patients hospitalized with CAP (n = 59) or COVID-19 pneumonia (n = 74) were compared regarding multiple characteristics, including cardiac biomarkers. In multivariable logistic regression analysis, differences were noted among various clinical features. Troponin I concentrations (p = 0.00028) and the Troponin I/NT-pro BNP ratio (p = 0.00048) were significantly higher in COVID-19 compared with CAP. After adjustment for age, these differences remained significant (troponin I p = 0.0019; ratio p = 0.00054), while BNP concentrations were now higher in CAP (p = 0.009). PCA demonstrated that BNP and NT-pro BNP contributed most strongly to the dominant cardiac biomarker signature, suggesting shared cardiopulmonary stress across both diseases. Exploratory subgroup analyses suggested higher troponin I levels among people living with HIV and COVID-19, although interaction modelling did not demonstrate significant effect modification by HIV status. Both CAP and COVID-19 pneumonia were associated with evidence of cardiac stress; however, COVID-19 demonstrated a relatively stronger myocardial injury signature characterized by higher troponin I concentrations and an increased Troponin I/NT-pro BNP ratio while CAP had evidence of greater hemodynamic cardiac strain, as evidenced by the higher levels of BNP. The findings suggest that the mechanisms of cardiac involvement may differ between viral and bacterial respiratory infections. Full article
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21 pages, 3412 KB  
Systematic Review
From Pandemic Innovation to Platform Diversification: A Systematic Review of Clinical and Preclinical Development of Non–SARS-CoV-2 mRNA Vaccines
by Shuaibu Abdullahi Hudu, Muhannad Alruwaili, Mohamed Soliman, Emad A. Morad, Ghusun M. Alhazimi and Abdulgafar Olayiwola Jimoh
Diseases 2026, 14(7), 230; https://doi.org/10.3390/diseases14070230 - 26 Jun 2026
Abstract
Background: Messenger RNA (mRNA) vaccines have emerged as a versatile platform beyond SARS-CoV-2, with expanding applications in infectious diseases and oncology. However, comprehensive evidence synthesis of non-SARS-CoV-2 mRNA vaccines remains limited. Methods: This systematic review followed PRISMA 2020 guidelines and was registered in [...] Read more.
Background: Messenger RNA (mRNA) vaccines have emerged as a versatile platform beyond SARS-CoV-2, with expanding applications in infectious diseases and oncology. However, comprehensive evidence synthesis of non-SARS-CoV-2 mRNA vaccines remains limited. Methods: This systematic review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD420261323500). MEDLINE, Embase, Web of Science, Scopus, ClinicalTrials.gov, and WHO ICTRP were systematically searched for studies published between 1 January 2000 and 28 February 2026. Eligible studies included phase I–III clinical trials and in vivo preclinical studies evaluating non-SARS-CoV-2 mRNA vaccines. Two reviewers independently screened studies, extracted data, and assessed risk of bias using RoB 2, ROBINS-I, and SYRCLE tools. Findings were synthesized narratively because of substantial heterogeneity. Results: A total of 40 studies met the eligibility criteria and were included in the review, comprising 20 clinical studies and 20 preclinical studies. Advanced clinical programs targeted influenza and respiratory syncytial virus (RSV), with phase III trials displaying seroconversion rates above 70% with good safety profiles. Preliminary phase I studies for HIV, cytomegalovirus, rabies, and personalized cancer mRNA vaccines showed promising humoral and cellular immune responses. Preclinical studies showed strong antibody and T-cell responses against malaria, tuberculosis, Group B Streptococcus, and Zika virus. Most adverse events were mild to moderate, while serious vaccine-related adverse events were uncommon. Conclusions: Non-SARS-CoV-2 mRNA vaccines demonstrate substantial translational potential across infectious disease and oncology applications. Although the vaccine candidates have demonstrated promising immunogenicity and safety, most are in the early stages of development. This highlights the need for large trials, long-term safety follow-up and better global representation. Full article
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19 pages, 3254 KB  
Article
Distinct Innate and Adaptive Immune Modules Differentially Associate with HIV Reservoir Size and Decay During Early Antiretroviral Therapy
by Wei-Zhe Li, Hui-Huang Huang, Hui-Fang Wang, Xia Li, Ming-Ju Zhou, Yu-Xuan Yang, You-Yuan Wang, Meng-Meng Zhu, Ying Sun, Si-Yuan Chen, Xing Fan, Yan-Mei Jiao, Jin-Wen Song, Ruo-Nan Xu, Cheng Zhen, Ming Shi, Chao Zhang and Fu-Sheng Wang
Cells 2026, 15(13), 1161; https://doi.org/10.3390/cells15131161 - 25 Jun 2026
Abstract
HIV reservoir size and decay represent distinct dimensions of viral persistence, yet whether they are governed by shared or separable immunological mechanisms during early antiretroviral therapy (ART) remains unclear. In this study, we employed multiparameter flow cytometry and bulk RNA sequencing to analyze [...] Read more.
HIV reservoir size and decay represent distinct dimensions of viral persistence, yet whether they are governed by shared or separable immunological mechanisms during early antiretroviral therapy (ART) remains unclear. In this study, we employed multiparameter flow cytometry and bulk RNA sequencing to analyze longitudinal immune profiles across 21 treatment-naïve people living with HIV before ART initiation and at 1 and 5 months thereafter. Our findings revealed an apparent dissociation between HIV-1 DNA levels and decay rates in peripheral blood, and the two indicators appear to be relatively independent dimensions of viral persistence. Specifically, lower HIV-1 DNA levels were associated with higher frequencies of cytotoxic and adaptive-like natural killer (NK) cell subsets, whereas faster HIV-1 DNA decay was linked to restored HIV-specific CD4+ and CD8+ T-cell responses during treatment. Notably, transcriptomic analyses uncovered divergent gene expression signatures related to B cell-associated immunity and type I interferon pathways, with individuals with higher HIV-1 DNA levels exhibiting elevated expression of immunoglobulin and interferon-stimulated genes, while faster decay correlated with enrichment of antiviral and complement-related genes. Collectively, these findings provide a preliminary characterization of immune correlates of peripheral blood total HIV-1 DNA dynamics in the early phase following ART initiation. This work offers potential immune clues for exploring the viral reservoir and generates testable hypotheses for validation in future large cohorts. Full article
(This article belongs to the Topic The Pathogenesis and Treatment of Immune-Mediated Disease)
27 pages, 4517 KB  
Article
HIV-V3Augur: A Novel Machine Learning Model for Predicting HIV-1 Tropism in Sub-Subtype A6 and CRF63_02A6, Predominant Variants in Russia and Countries of the Former Soviet Union
by Kirill Elfimov, Ludmila Gotfrid, Alina Nokhova, Mariya Gashnikova, Vasiliy Ekushov, Maksim Halikov, Irina Osipova, Dmitriy Baboshko, Andrey Murzin, Ivan Kondeikin, Arina Kiryakina, Aleksey Totmenin, Aleksandr Agaphonov and Natalya Gashnikova
Viruses 2026, 18(7), 703; https://doi.org/10.3390/v18070703 - 25 Jun 2026
Abstract
Determining HIV-1 tropism provides the prognosis of HIV infection and is required before prescribing maraviroc, an entry inhibitor that blocks the interaction between the viral gp120 and the CCR5 coreceptor. However, existing prediction algorithms have been developed primarily for the globally most prevalent [...] Read more.
Determining HIV-1 tropism provides the prognosis of HIV infection and is required before prescribing maraviroc, an entry inhibitor that blocks the interaction between the viral gp120 and the CCR5 coreceptor. However, existing prediction algorithms have been developed primarily for the globally most prevalent subtypes (B, C, and CRF01_AE) and often show reduced performance for other HIV-1 genetic variants. Sub-subtype A6 and circulating recombinant form CRF63_02A6 dominate the HIV-1 epidemic in Russia and other Former Soviet Union (FSU) countries, yet the reliability of tropism prediction for these viruses remains virtually unexplored. We phenotypically determined the tropism of 25 clinical isolates (11 R5, 1 X4, and 7 dual-tropic R5/X4) using U87.CD4.CCR5 and U87.CD4.CXCR4 cell lines and performed a comparative analysis of eight existing genotypic tools (Geno2pheno, WebPSSM, T-CUP 2.0, the Delobel/Garrido rules, and others) or their modifications on a combined dataset that included Los Alamos National Laboratory (LANL) reference sequences (subtypes A, B, C, CRF01_AE, and CRF02_AG) and our laboratory-derived isolates. Most models achieved high accuracy for globally prevalent subtypes (≈95% for B, C, and CRF01_AE) but showed markedly reduced performance for sub-subtype A6 (best accuracy among existing models, 85%) and CRF63_02A6 (best accuracy, 72%), with a poor balance between sensitivity and specificity. To address this problem, we developed HIV-V3Augur, an ensemble stacking model based on the Random Forest and Support Vector Machine (SVM) machine learning algorithms, trained on Pseudo Amino Acid Composition (PseAAC) and Relative Synonymous Codon Usage (RSCU) features with 10-fold stratified cross-validation. HIV-V3Augur achieved an accuracy of 77%, sensitivity of 79%, and specificity of 79% on sub-subtype A6, and on CRF63_02A6 it reached an accuracy of 95%, sensitivity of 87%, and specificity of 100%. Cross-validation demonstrated that HIV-V3Augur represents a balanced genotypic tropism prediction tool for understudied HIV-1 variants circulating in the FSU region. HIV-V3Augur can be used locally through a graphical user interface. Full article
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13 pages, 4970 KB  
Article
Non-Canonical Binding of Nelfinavir in HIV-1 Protease Variants Reveals Structural Mechanisms of Antiretroviral Resistance
by Christian Cadena-Cruz, Marcio De Avila-Arias, Fabio Guzmán, Mariana Pérez, María Angelica Zuluaga, Elkin Navarro Quiroz, Alejandro Angulo, Luz Elena Prieto Garcerant, Hector Rodríguez Rojas, Dinno Alberto Fernández Chica, Guillermo Cervantes and Jose Luis Villarreal-Camacho
Viruses 2026, 18(7), 701; https://doi.org/10.3390/v18070701 (registering DOI) - 25 Jun 2026
Abstract
Background: Antiretroviral resistance-associated mutations, within the broader context of HIV-1 genetic variability, represent a growing challenge for HIV-1 control, highlighting the need for continuous molecular surveillance and mechanistic understanding of drug resistance. This study aimed to characterize mutations in the pol gene associated [...] Read more.
Background: Antiretroviral resistance-associated mutations, within the broader context of HIV-1 genetic variability, represent a growing challenge for HIV-1 control, highlighting the need for continuous molecular surveillance and mechanistic understanding of drug resistance. This study aimed to characterize mutations in the pol gene associated with resistance to protease inhibitors and to explore their structural implications. Methods: Viral RNA was extracted from plasma samples of HIV-positive patients, and a 266 bp fragment of the HIV-1 pol gene was amplified by RT-PCR and sequenced using the Sanger method. Sequences showing ≥98% homology were aligned and analyzed using MEGA v11 and the Stanford HIV Drug Resistance Database to identify resistance-associated mutations, while viral subtypes were determined using COMET, jpHMM-HIV, and STAR tools. Amino acid sequences were used for structural modeling with AlphaFold, followed by molecular docking with Nelfinavir using the CB-Dock2 server. Results: Four samples exhibited resistance-associated profiles, including high-level, intermediate, and low-level resistance, with one isolate showing high-level resistance to multiple protease inhibitors. Structural analyses revealed that Nelfinavir preferentially binds to alternative hydrophobic cavities rather than the canonical catalytic site, lacking direct interactions with the Asp25/Asp25′ dyad. Conclusions: These findings suggest a structural mechanism of resistance based on non-canonical ligand binding that may impair effective protease inhibition. Full article
(This article belongs to the Section General Virology)
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16 pages, 7972 KB  
Article
Trends and Projected Burden of HIV/AIDS in Kazakhstan, 2010–2030: A Comparative Analysis Using GBD 2023 Estimates
by Indira Karibayeva, Gulzar Shah, Nikolay Lunchenkov, Roza Kuanyshbekova, Kuanysh Shonbay and Botagoz Turdaliyeva
Trop. Med. Infect. Dis. 2026, 11(7), 171; https://doi.org/10.3390/tropicalmed11070171 - 24 Jun 2026
Viewed by 121
Abstract
Background: HIV/AIDS remains a major global public health challenge, with persistent regional disparities in burden and progress toward the UNAIDS 95–95–95 targets. This study assessed temporal trends in the HIV/AIDS burden in Kazakhstan, compared them with Central Asia and global patterns, and projected [...] Read more.
Background: HIV/AIDS remains a major global public health challenge, with persistent regional disparities in burden and progress toward the UNAIDS 95–95–95 targets. This study assessed temporal trends in the HIV/AIDS burden in Kazakhstan, compared them with Central Asia and global patterns, and projected trends through 2030. Methods: We conducted a population-level analysis using Global Burden of Disease 2023 data, examining age-standardized rates (per 100,000) of incidence, prevalence, mortality, disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) from 2010 to 2023. Trends were quantified using percent change and average annual percentage change, with projections based on log-linear models. Results: Between 2010 and 2023, prevalence in Kazakhstan increased by 332.1% and incidence by 111.0%, contrasting with the decline in global incidence (−24.7%). Mortality decreased (−32.7%), along with DALYs (−28.8%) and YLLs (−37.1%), while YLDs increased by 135.5%, indicating a shift toward a chronic disease burden. In 2023, Kazakhstan had a lower overall burden than global estimates but showed steeper increases in incidence and prevalence. Age-specific analyses indicated the largest increases among adults aged 30–69 years. Under current trend assumptions, projections suggest continued growth in prevalence and incidence, with modest mortality declines through 2030, though these trajectories do not account for future changes in prevention coverage, treatment access, or policy. Conclusions: Kazakhstan is undergoing a transition toward a chronic HIV epidemic, underscoring the need to strengthen prevention, expand PrEP and testing coverage, and address structural barriers to achieve epidemic control. Full article
(This article belongs to the Special Issue HIV-1 Dynamics and Public Health)
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28 pages, 6390 KB  
Article
miR-23a-3p as a Biomarker Associated with Prediabetes in People Living with HIV: An Integrative Analysis of Inflammatory, Metabolic, and Insulin Resistance Signatures
by Paula Catalina Méndez-Ríos, Yusnier Lázaro Díaz-Rodríguez, Luis F. Jave-Suarez, Luz A. González-Hernández, Jaime F. Andrade-Villanueva, Monserrat Álvarez-Zavala, Pedro Martínez-Ayala, Vida V. Ruiz-Herrera, Elsa Janneth Anaya-Ambriz and Karina Sánchez-Reyes
Int. J. Mol. Sci. 2026, 27(13), 5658; https://doi.org/10.3390/ijms27135658 - 23 Jun 2026
Viewed by 175
Abstract
People living with HIV (PLWHIV) have an increased risk of developing metabolic disorders, including type 2 diabetes (T2D), partly driven by chronic low-grade inflammation and immune dysregulation. This study evaluated the potential role of circulating miR-23a-3p as a possible early biomarker of prediabetes [...] Read more.
People living with HIV (PLWHIV) have an increased risk of developing metabolic disorders, including type 2 diabetes (T2D), partly driven by chronic low-grade inflammation and immune dysregulation. This study evaluated the potential role of circulating miR-23a-3p as a possible early biomarker of prediabetes (preT2D) in PLWHIV. In this cross-sectional study, 80 adults were divided into five groups (n = 16 each): normoglycemic PLWHIV, PLWHIV with preT2D, PLWHIV with T2D, HIV-negative individuals with T2D, and controls. Clinical, anthropometric, biochemical, inflammatory, and insulin resistance (IR) markers were assessed, while plasma miR-23a-3p was quantified by digital PCR (dPCR). Bioinformatic network analysis was performed to identify potential molecular targets. PLWHIV with T2D showed the most unfavorable metabolic and inflammatory profile, including higher HbA1c, triglycerides, IL-6, TNF-α, hs-CRP, and GDF-15. In contrast, PLWHIV with preT2D exhibited significant overexpression of miR-23a-3p, whereas lower levels were observed in normoglycemic PLWHIV. miR-23a-3p correlated positively with IL-6 and GDF-15. ROC analyses showed good discriminative performance of miR-23a-3p for preT2D in PLWHIV (AUC = 0.80), and logistic regression confirmed its association with preT2D. In silico network analysis suggested potential inflammatory and metabolic targets of miR-23a-3p; however, these findings require experimental validation. These findings suggest that miR-23a-3p may represent a potential early biomarker of preT2D and immunometabolic dysfunction in PLWHIV. Full article
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16 pages, 1148 KB  
Systematic Review
Torque Teno Virus (TTV) Plasma Load and Immune Reconstitution in People Living with HIV: A Systematic Review
by Federico Cesanelli, Ottavia Nozza, Martina Salvi, Maria Alberti, Irene Scarvaglieri, Giorgio Tiecco, Francesca Mosti, Maria Antonia De Francesco and Eugenia Quiros-Roldan
Microorganisms 2026, 14(6), 1386; https://doi.org/10.3390/microorganisms14061386 - 22 Jun 2026
Viewed by 137
Abstract
Background: Torque teno virus (TTV) is a ubiquitous, non-pathogenic component of the human virome whose role in people living with HIV (PLWH), particularly during antiretroviral therapy (ART)-mediated immune reconstitution, remains unclear. This systematic review aimed to synthesize available evidence on TTV viral load [...] Read more.
Background: Torque teno virus (TTV) is a ubiquitous, non-pathogenic component of the human virome whose role in people living with HIV (PLWH), particularly during antiretroviral therapy (ART)-mediated immune reconstitution, remains unclear. This systematic review aimed to synthesize available evidence on TTV viral load in PLWH, focusing on its relationship with immunological markers. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive literature search was conducted in MEDLINE, Web of Science, and Scopus in January 2026 to identify studies assessing plasma TTV viral load before and/or during ART and reporting immunological outcomes. Eligible studies included prospective and retrospective longitudinal studies, cross-sectional studies, and mixed designs assessing plasma TTV viral load in relation to ART status and immune recovery markers. Results: Thirteen studies (n = 1700 PLWH) were included, predominantly observational and conducted in adult populations. Most studies (76.9%) reported a significant inverse association between TTV viral load and CD4 T-cell count, while all studies assessing HIV viral load found a direct correlation with TTV levels. An inverse relationship with the CD4/CD8 ratio was consistently observed where evaluated. Higher TTV loads were reported in ART-naïve individuals and in those with advanced immunosuppression, with longitudinal studies indicating a general decline during ART. Overall, methodological heterogeneity and moderate risk of bias were common. Conclusions: TTV viral load shows a consistent inverse association with CD4 cell count and may reflect global immune dysfunction in PLWH beyond conventional markers. However, its clinical utility remains investigational due to the heterogeneity in the study design, limited data on longitudinal dynamics, and lack of standardized assays and thresholds. Full article
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37 pages, 11390 KB  
Review
Human Papillomavirus Infection Across the Immunological Spectrum: Clinical Expression, Colposcopic Challenges, and Therapeutic Implications
by Antonio Braga, Gustavo Ribeiro Lima, Karine Mello Duvivier, Edward Araujo Júnior, Caroline Alves de Oliveira Martins, Isabel Cristina Chulvis do Val Guimarães and Susana Cristina Aidé Viviani Fialho
Diagnostics 2026, 16(12), 1932; https://doi.org/10.3390/diagnostics16121932 - 22 Jun 2026
Viewed by 209
Abstract
Human papillomavirus (HPV) infection is a major driver of anogenital disease and virus-related carcinogenesis. Although most infections resolve spontaneously, persistent infection with high-risk genotypes may progress to high-grade squamous intraepithelial lesions (HSILs) and cancer, particularly in the setting of impaired immune surveillance. Unlike [...] Read more.
Human papillomavirus (HPV) infection is a major driver of anogenital disease and virus-related carcinogenesis. Although most infections resolve spontaneously, persistent infection with high-risk genotypes may progress to high-grade squamous intraepithelial lesions (HSILs) and cancer, particularly in the setting of impaired immune surveillance. Unlike previous HPV-related reviews focused primarily on cervical disease, vaccination, or isolated immunosuppressed populations, this narrative review comparatively examines the clinical expression, colposcopic findings, screening strategies, and therapeutic implications of HPV-related disease across the immunological spectrum. This narrative review provides an integrative synthesis of HPV-related disease in the female lower genital tract across the immunological spectrum. A structured, non-systematic search of PubMed/MEDLINE, Scopus, and Web of Science was conducted using terms related to “human papillomavirus”, “HPV”, “cervical intraepithelial neoplasia”, “colposcopy”, “immunosuppression”, “HIV”, and “vaccination”. Immunosuppressed populations, including individuals living with HIV, transplant recipients, and patients receiving immunosuppressive therapy, exhibit higher rates of persistent infection, multifocal disease, recurrence, and progression to HSIL and invasive malignancy. These patients also present greater diagnostic complexity, broader anatomical involvement, and reduced response to conventional treatment. Rather than representing a uniform condition, HPV-related disease reflects a biologically dynamic spectrum shaped by host immune competence. This review highlights the distinct clinical, colposcopic, and therapeutic challenges observed in immunosuppressed populations and reinforces the need for individualized, risk-adapted strategies integrating contemporary advances in screening, vaccination, and HPV-related disease management. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Treatment of Gynecological Infections)
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13 pages, 664 KB  
Article
Has the Expected Shift in HIV-Related Cancers Occurred? Findings from a Long-Term HIV Cohort in Turkey
by İnci Yılmaz Nakir, Melike Nur Özçelik, Rumeysa Gülistan Karaduman and Esra Zerdali
J. Clin. Med. 2026, 15(12), 4818; https://doi.org/10.3390/jcm15124818 - 21 Jun 2026
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Abstract
Background/Objectives: Despite widespread antiretroviral therapy (ART) use, whether the expected transition from AIDS-defining to non-AIDS-defining cancers has occurred in settings with persistent late HIV presentation remains unclear. We examined long-term cancer patterns, determinants, and survival outcomes in a large HIV cohort. Methods [...] Read more.
Background/Objectives: Despite widespread antiretroviral therapy (ART) use, whether the expected transition from AIDS-defining to non-AIDS-defining cancers has occurred in settings with persistent late HIV presentation remains unclear. We examined long-term cancer patterns, determinants, and survival outcomes in a large HIV cohort. Methods: This retrospective, single-center cohort included 1419 people living with HIV followed between 2006 and 2024. Patients who developed malignancy were classified as AIDS-defining cancers (ADC) or non-AIDS-defining cancers (NADC). Immuno-virological parameters were assessed at HIV and cancer diagnosis. Survival was analyzed using Kaplan–Meier methods, and predictors of mortality were evaluated using Cox proportional hazards regression. Determinants of ADC development were assessed using multivariable logistic regression. Temporal changes were evaluated by trend analysis. Results: Sixty-six patients (4.6%) developed malignancy (31 ADC, 35 NADC). Late HIV presentation was common, with 72.7% having CD4+ T-lymphocyte counts < 350 cells/mm3 at cancer diagnosis, particularly among ADC cases. Most ADCs (93.5%) occurred within 24 months of HIV diagnosis. Overall survival did not differ between ADC and NADC groups (log-rank p = 0.14). Although mortality declined after 2015, temporal changes in ADC and NADC proportions did not reach statistical significance (p = 0.14). In Cox regression analysis, viral suppression before death or last follow-up was independently associated with lower mortality risk (HR 0.12; 95% CI 0.05–0.31). Lower CD4+ T-lymphocyte counts were associated with ADC development, and a CD4+ T-lymphocyte threshold of 295 cells/mm3 showed good discriminative performance (AUC = 0.83), although this cutoff should be interpreted cautiously due to the lack of external validation. Conclusions: In this long-term cohort from Türkiye, a clear epidemiological transition from ADC to NADC could not be demonstrated. The cancer spectrum remained strongly influenced by late HIV presentation and advanced immunodeficiency. Sustained viral suppression was independently associated with lower mortality risk, supporting the importance of early HIV diagnosis, timely ART initiation, and sustained virological control. Full article
(This article belongs to the Section Infectious Diseases)
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14 pages, 1041 KB  
Article
Amplicon-Based Multiregion Genomic Characterization of HIV-1 in a Tertiary-Care Hospital in Mexico: Antiretroviral Resistance Mutations and Subtype Diversity
by Eduardo García-Moncada, Enoc Mariano Cortés-Malagón, Jesús Alejandro Pineda-Migranas, Montserrat Ruiz Santana, Iliana Alejandra Cortés-Ortíz, José Francisco Escutia Domínguez, Daniel Agustín Bravata-Alcántara, Gustavo Acosta-Altamirano, Saúl David Razo-González, Manuel Alberto Castillo Mendez, Mónica Sierra-Martínez and Juan Carlos Bravata-Alcántara
Int. J. Mol. Sci. 2026, 27(12), 5571; https://doi.org/10.3390/ijms27125571 - 20 Jun 2026
Viewed by 169
Abstract
Human immunodeficiency virus type 1 exhibits extensive genetic diversity, which has important implications for molecular epidemiology, recombinant-pattern assessment, and antiretroviral resistance surveillance. In Mexico, HIV-1 molecular surveillance has historically relied mainly on partial pol gene sequencing, limiting the ability to compare lineage assignments [...] Read more.
Human immunodeficiency virus type 1 exhibits extensive genetic diversity, which has important implications for molecular epidemiology, recombinant-pattern assessment, and antiretroviral resistance surveillance. In Mexico, HIV-1 molecular surveillance has historically relied mainly on partial pol gene sequencing, limiting the ability to compare lineage assignments across gag, pol, and env regions. We analyzed plasma samples from 40 treatment-naïve adults receiving care at a tertiary-care hospital in Mexico using a commercial amplicon-based multiregion HIV-1 genomic sequencing workflow. DeepChek® was used as the primary workflow for read processing, mutation calling, region-level subtype assignment, and antiretroviral resistance interpretation. Resistance interpretation was restricted to antiretroviral target regions with sufficient coverage, mainly reverse transcriptase, protease, integrase, and capsid, when available. Drug resistance mutations were identified in 6/40 participants (15.0%) when mutation-level resistance findings in RT, PR, and IN were considered; one additional sample showed a capsid inhibitor-nonsusceptible NGS call. NNRTI-associated findings were identified in 2/40 patients (5.0%), whereas NRTI- and PI-associated findings were identified in 1/40 patients (2.5%). Accessory or secondary INSTI-associated substitutions were detected in 2/40 patients (5.0%). Region-level subtype analysis revealed frequent discordant assignments across amplified segments, which is consistent with complex mosaic profiles; however, these findings are interpreted as region-level subtypes and recombinant-pattern assignments rather than continuous whole-genome recombination maps. One sample had insufficient RT/PROT/INT coverage for drug resistance interpretation in the complete DeepChek report and was retained only for regions meeting quality thresholds. These findings support the value of multiregion HIV-1 sequencing for local molecular surveillance while emphasizing the need for transparent region-level coverage reporting, cautious interpretation of recombinant-pattern calls, and transparent repository reporting. Full article
(This article belongs to the Special Issue Genomics of Human Disease)
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12 pages, 1134 KB  
Article
A Multilevel Analysis of HIV Care Outcomes Across Age, Race, and Housing Among United States Women Veterans
by Giselle Day, Amber B. Amspoker, Alan Z. Sheinfil, Liang Chen, Emmanuel Guajardo, Maria E. Fernandez, Cici Bauer, Irene Tamí-Maury and Jan Lindsay
Healthcare 2026, 14(12), 1781; https://doi.org/10.3390/healthcare14121781 - 20 Jun 2026
Viewed by 184
Abstract
Background: Women veterans with HIV represent a growing, diverse population within the Veterans Health Administration (VHA). This study examined HIV care continuum outcomes among women veterans using a multilevel intersectional approach. Methods: We conducted a retrospective analysis of 1154 women veterans with HIV [...] Read more.
Background: Women veterans with HIV represent a growing, diverse population within the Veterans Health Administration (VHA). This study examined HIV care continuum outcomes among women veterans using a multilevel intersectional approach. Methods: We conducted a retrospective analysis of 1154 women veterans with HIV in VHA care in fiscal year 2022, with outcomes assessed in fiscal year 2023. We applied Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA) to evaluate how combinations of social positions (age, race/ethnicity, housing status) were associated with HIV outcomes. Results: MAIHDA models showed that younger age (<45 years) and being unhoused were consistently associated with lower odds of care engagement and viral suppression than midlife (45–64) and older (65+) housed women veterans. Additionally, predicted probability analyses revealed distinct clustering patterns. Younger non-Hispanic White women consistently ranked among the lowest performing strata across all outcomes, while midlife and older Hispanic and non-Hispanic Black women veterans clustered among the highest. Variance Partition Coefficients from null models were modest (1.8–3.0%). Fully adjusted models showed no remaining between-stratum variance, suggesting that the included social positions explained the observed differences in our dataset. Conclusions: These findings highlight disparities in HIV care engagement concentrated among specific groups and reinforce the importance of addressing individual- and system-level barriers to engagement and continuity of care among women Veterans in VHA care. Full article
(This article belongs to the Section Chronic Care)
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