To evaluate the associations of plasma EBV-DNA and tumor EBV status with clinical outcomes in patients with AIDS-related non-Hodgkin lymphoma (ARL). We retrospectively analyzed ARL patients diagnosed at Shanghai Public Health Clinical Center between 2013 and 2021. Tumor EBV status was determined by EBV-encoded RNA (EBER) in situ hybridization, and plasma EBV-DNA was quantified using real-time PCR. Survival outcomes were evaluated using Kaplan–Meier analysis and Cox regression. Longitudinal EBV-DNA patterns during chemotherapy were classified into four groups: persistently negative, persistently positive, clearance, and conversion. Among 183 ARL patients, 99 underwent tumor EBER testing with 45.5

BACKGROUND:Tuberculosis (TB) remains the leading cause of death among people living with HIV (PLWH). While tuberculosis preventive treatment (TPT) is universally recommended for PLWH with latent TB infection (LTBI), its necessity for interferon-gamma release assay (IGRA)-negative individuals initiating antiretroviral therapy (ART) is controversial. Therefore, this study aimed to investigate whether TPT is necessary in this specific population. METHODS:We conducted a retrospective cohort study of ART-naïve PLWH with a negative IGRA without prior anti-tuberculosis drug use or active TB at Shanghai Public Health Clinical Center from 2020 to 2024. Demographic characteristics, laboratory results, and TB occurrence during follow-up were recorded. Kaplan-Meier analysis, Cox proportional hazards models, and restricted cubic splines were used to identify risk factors and model the dose-response relationship between CD4 + T-cell count and TB risk. RESULTS:Among 686 participants (89.4% male, median age 41), the median CD4 + T-cell count was 35.52 cells/µL. During a 26-month median follow-up, 22 patients developed TB (incidence: 13.41/1000 person-years). All TB cases occurred in the 583 patients with CD4 + T-cell count < 200 cells/µL (incidence: 15.61/1000 person-years), while no events occurred in those with CD4 + T-cell count ≥ 200 cells/µL. Lower CD4 + T-cell count and residence in high-risk areas (adjusted Hazard Ratio [aHR] = 3.65, 95% CI: 1.35-9.89) were independent risk factors for active TB. A continuous log-linear inverse relationship between CD4 + T-cell count and TB risk was identified, with progressively higher risk at lower CD4 levels. CONCLUSION:IGRA-negative PLWH with CD4 + T-cell count < 200 cells/µL and high-risk area residence may be considered as priority candidates for TPT. This risk-stratification framework warrants prospective validation.

Cytomegalovirus (CMV) pneumonia presents diagnostic challenges in AIDS patients, as plasma monitoring often fails to reflect pulmonary viral burden. This retrospective study evaluated the prognostic value of bronchoalveolar lavage fluid (BALF) CMV DNA loads in 189 AIDS patients with pulmonary infections and CD4+ T cell counts < 200 cells/μL. CMV DNA in BALF and plasma was quantified to analyze associations with immune status and 90-day all-cause mortality. CMV detection was significantly more frequent in BALF (49.7%) than plasma (26.6%), indicating viral compartmentalization. An optimal BALF cutoff of 10,000 copies/mL was established for mortality prediction. Patients exceeding this threshold exhibited significantly lower CD4+ counts, increased mechanical ventilation requirements (34.4% vs. 11.5%), and prolonged hospital stays. Crucially, a BALF CMV load > 10,000 copies/mL was identified as an independent predictor of 90-day mortality (adjusted odds ratio = 3.78; 95% CI: 1.12–12.71). In conclusion, pulmonary CMV replication is prevalent and often compartmentalized in AIDS patients. A BALF CMV DNA load exceeding 10,000 copies/mL serves as a biomarker of profound immunosuppression and independently predicts poor clinical outcomes, highlighting the necessity of quantitative BALF monitoring for risk stratification.

Aims:This study aims to systematically compare the clinical characteristics of tuberculosis (TB) and nontuberculous mycobacterial (NTM) diseases in AIDS patients,and to identify independent predictors for differential diagnosis. Methods:Clinical data of AIDS patients co-infected with TB or NTM at Shanghai Public Health Clinical Center (January 2019 - January 2024) were retrospectively analyzed. Univariate comparisons were performed using t-test, Mann-Whitney U test, χ2 or Fisher's exact test, with Bonferroni correction for multiple comparisons. Multivariate binary logistic regression (Enter method) was used to adjust for age, gender, CD4+ T-cell count, C-reactive protein (CRP), procalcitonin, neutrophil count, miliary nodules, and superficial lymphadenopathy. Results:A total of 494 patients were included (AIDS/TB: 206, AIDS/NTM: 288). The predominant NTM species was Mycobacterium avium (68.2%), followed by Mycobacterium kansasii (13.6%) and Mycobacterium intracellulare (10.9%). After Bonferroni correction, AIDS/NTM patients had significantly higher rates of Pneumocystis jirovecii pneumonia, cytomegalovirus infection, and progressive multifocal leukoencephalopathy (all P < 0.0083). Among clinical symptoms, only enlarged lymph nodes remained significantly more common in the TB group after correction (P = 0.002). Multivariate analysis showed that male gender (adjusted OR for NTM vs. TB = 0.451, 95% CI: 0.208-0.979, P = 0.044), higher CD4+ count (per 10 cells/μL: OR = 0.98, 95% CI: 0.96-0.99, P = 0.005), higher CRP (per 10 mg/L: OR = 0.90, 95% CI: 0.86-0.95, P < 0.001), higher neutrophil count (OR = 0.903 per 1 × 10(Akokuebere et al., 20249)/L, 95% CI: 0.836-0.976, P = 0.010), presence of miliary nodules (OR = 0.079, 95% CI: 0.027-0.233, P < 0.001), and presence of superficial lymphadenopathy (OR = 0.565, 95% CI: 0.327-0.977, P = 0.041) were independently associated with lower odds of NTM disease (i.e., associated with TB). Imaging revealed that only miliary nodules remained significantly more common in TB after Bonferroni correction (P < 0.001). Conclusions:While AIDS/TB and AIDS/NTM share many clinical similarities, the presence of miliary nodules, superficial lymphadenopathy, higher inflammatory markers (CRP, neutrophils), higher CD4+ count, and male gender favor TB. These findings can assist clinicians in differentiating the two infections when rapid microbiological results are unavailable. The high prevalence of Mycobacterium avium (68.2%) suggests that empirical therapy for suspected NTM in severely immunocompromised AIDS patients in Shanghai should cover the Mycobacterium avium complex (MAC). Prospective multicenter studies with pre-specified outcomes are needed to validate our findings.

HIV-1 evades host immunity via a number of virally encoded mediators. Here we show that the HIV-1 antisense protein (ASP) evades host immunity by interfering with the type I interferon (IFN-I) response. Mechanistically, host prolyl hydroxylase 3 (PHD3) hydroxylates ASP at Pro47, enabling the recruitment of the RING finger protein 114 (RNF114) to TANK-binding kinase 1 (TBK1). Subsequently, RNF114 mediates K6-linked ubiquitination of TBK1 at Lys236, suppressing TBK1 activation and the downstream IFN-I response. Conversely, mutation of ASP at Pro47 abolishes this inhibitory effect. In humanized mice, either ASP deletion or treatment with the RNF114 inhibitor EN219 or the PHD3 inhibitor Molidustat enhances antiviral immunity and reduces viral replication. Clinically, RNF114 and PHD3 transcript levels exhibit a positive correlation with viral load in treatment-naive patients. Here we show a distinct HIV-1 immune evasion mechanism involving proline hydroxylation and K6-linked ubiquitination, highlighting therapeutic potential.

This study evaluates the potential of plasma extracellular vesicle (EV)-associated miRNAs as diagnostic and differential-diagnostic biomarkers to distinguish tuberculosis (TB) from non-tuberculous mycobacterial infection (NTM) among AIDS patients. A cohort of 125 AIDS patients admitted to the Infectious Diseases and Immunology Department of Shanghai Public Health Clinical Center from January 2021 to January 2024 was categorized into AIDS/TB, AIDS/NTM, and AIDS control groups; in the discovery phase, 15 cases (AIDS/TB: 3, AIDS/NTM: 9, AIDS controls: 3) were used to isolate plasma-derived EVs and perform high-throughput sequencing to construct miRNA expression profiles, followed by validation in a large-sample cohort of 110 cases using qPCR. Diagnostic and differential diagnostic value were evaluated with ROC curves, area under the curve (AUC), and the Youden index. In the discovery phase, differentially expressed EV-associated miRNAs were observed among the three groups and among different NTM species; miR-374a-5p and miR-652-3p were markedly downregulated in AIDS/NTM versus AIDS/TB and AIDS controls, while let-7c-5p was upregulated in both AIDS/NTM and AIDS/TB versus AIDS controls. In the validation phase (n=110), miR-374a-5p showed no significant difference between AIDS/TB and AIDS controls but was lower in AIDS/NTM; miR-652-3p was higher in AIDS/TB than controls and lower in AIDS/NTM than controls and AIDS/TB; let-7c-5p was significantly higher in both AIDS/TB and AIDS/NTM than controls, with AIDS/NTM higher than AIDS/TB. ROC analyses yielded: AIDS control vs AIDS/NTM—miR-374a-5p AUC 0.7263, miR-652-3p AUC 0.9947, let-7c-5p AUC 1.0000; AIDS control vs AIDS/TB—miR-374a-5p AUC 0.6800, miR-652-3p AUC 0.7900, let-7c-5p AUC 1.0000; AIDS/NTM vs AIDS/TB—miR-374a-5p AUC 0.8220, miR-652-3p AUC 0.9993, let-7c-5p AUC 0.6613. Collectively, plasma EV-associated miR-374a-5p, miR-652-3p, and let-7c-5p show potential as diagnostic and differential-diagnostic biomarkers for distinguishing TB from NTM infections in AIDS patients, offering a prospective direction for TB/NTM diagnostic strategies in this population.

Long-term use of tenofovir disoproxil fumarate (TDF) is associated with renal tubular dysfunction and bone mineral loss. In virologically suppressed people living with HIV (PLWH), optimizing antiretroviral therapy requires maintaining viral suppression while minimizing cumulative drug-related toxicity. We therefore evaluated the efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) in Chinese PLWH with TDF-related renal or bone toxicity. This prospective, single-center, open-label cohort study enrolled adults with HIV-1 RNA < 40 copies/ml for ≥ 6 months on TDF-based regimens and evidence of TDF-associated renal or bone toxicity. Participants were switched to DTG/3TC and followed for 48 weeks. The primary endpoint was virological failure at week 48 (FDA Snapshot algorithm). Secondary endpoints included changes in CD4 + T-cell counts, renal tubular biomarkers, bone mineral density (BMD), metabolic parameters, and safety outcomes. One hundred participants were enrolled; 91 completed the study per protocol. Median age was 45 years and 90

Dolutegravir (DTG) plus lamivudine (3TC) is one of the preferred treatment regimens for HIV, yet evidence remains limited for people living with HIV (PLWH) with high baseline viral load. This study aims to evaluate the effectiveness of DTG/3TC in treatment-naive PLWH with baseline viral load > 500,000 copies/mL in China. In this real-world multicenter cohort study, PLWH with baseline viral load (VL) > 500,000 copies/mL who initiated DTG/3TC were recruited across 18 clinical sites in China. Matched participants from the same sites with lower baseline VL were also included as a control group. Participants were followed for 48 weeks. The primary endpoint was virological suppression (HIV-1 RNA < 50 copies/mL) at week 48 using the US Food and Drug Administration snapshot algorithm. Of the 375 PLWH enrolled, 150 were classified into the high VL group and 225 into the low VL group. Baseline median HIV-1 RNA was 5.99 and 5.07 log10 copies/mL, respectively. At week 48, virologic suppression was achieved in 88.0

BACKGROUND:The impact of antiretroviral therapy (ART) adherence following cancer diagnosis on survival outcomes among people living with HIV (PLWH) with cancer remains unclear. METHODS:We conducted a retrospective study among PLWH with cancer from a major infectious disease hospital in Shanghai, China. Cox proportional hazards models were used to investigate factors associated with all-cause mortality among PLWH with cancer, with a particular emphasis on ART adherence following cancer diagnosis. ART adherence was measured as the proportion of days covered (PDC) by antiretroviral drugs, and in the primary analysis, patients' ART adherence was dichotomized using an 80% threshold. Furthermore, we conducted sensitivity analyses, adjusting the cutoff values for adherence rates (85%, and 90%). RESULTS:A total of 428 PLWH with cancer (355 [82.9%] male, median age at cancer diagnosis 51.84[IQR, 37.02-59.62]) were included, comprising 131 cases of AIDS-defining cancers (ADCs) and 297 non-AIDS-defining cancers (NADCs). The median ART adherence following cancer diagnosis was 87.7% (IQR, 69.6%-96.0%). In multivariate analyses, lower ART adherence (<80%) after cancer diagnosis was independently associated with an increased risk of death (HR=2.03, P < 0.001). By contrast, none of the HIV immunovirological status variables measured at cancer diagnosis showed a significant association with increased mortality. Similar patterns were observed across cancer subgroups, including ADCs, NADCs, and lymphomas. CONCLUSIONS:ART adherence following cancer diagnosis is essential to survival among PLWH with cancer. The integration of ART adherence support in HIV routine care may contribute to improved survival outcomes in PLWH with cancer.

Viral reservoir presents a significant challenge in HIV-1 cure. We previously observed that Thymosin α1 (Tα1) may restrict the reservoir through the IL-15 pathway. However, the precise mechanism remains to be fully elucidated. Peripheral blood mononuclear cells (PBMCs) were obtained from people living with HIV-1 (PLWH). In vitro, THP-1 cells were differentiated into mature monocyte-derived dendritic cells (MoDCs) and co-cultured with PBMCs under various conditions. Intracellular HIV-1 p24 levels, CD8+ T and NK cell functionality, and reservoir size were evaluated. In vitro, Tα1 stimulation of MoDCs resulted in significant immune response and secretion of IL-15/RA complex (p < 0.001). This interaction with IL-2 Rβ/γ receptors on T cells enhanced the intracellular secretion of CCL3/5, IFN-γ, and TNF-α in CD8+ T cells (p < 0.05), which inhibited p24 levels in CD4+ T cells (p = 0.002), and reduced HIV-1 integrated DNA levels (p = 0.012). Furthermore, the secretion levels of IFN-γ, TNF-α and GZMB in NK cells and proportion of CD8+ TVM cells significantly increased following co-culture. These alterations were found to be markedly inversely associated with reservoir size and reactivation. However, these effects were observed in PBMCs from immunological responders (CD4+ T cell count > 350 cells/µL) rather than nonresponders. Tα1 enhances CD8+ T cell function, promotes TVM proliferation, and suppresses reservoir size and reactivation via IL-15 pathway activation in dendritic cells, which warrants testing in functional cure trials in the future.

ObjectiveTo characterize gut microbiome alterations and microbial translocation in human immunodeficiency virus (HIV)/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infected patients and identify microbial signatures associated with COVID-19 severity.MethodsIn this cohort study, blood and fecal samples from 38 HIV/AIDS patients (20 SARS-CoV-2 co-infected [PC group]; 18 SARS-CoV-2-negative [NC group]) were analyzed. The PC group was stratified by COVID-19 severity: mild-to-moderate (PC1, n=13), severe-to-critical (PC2, n=3), and mixed infections (PC3, n=4). Serum lipopolysaccharide (LPS), soluble CD14 (sCD14), and zonulin levels were measured to assess microbial translocation and gut barrier integrity. Fecal metagenomic profiling was performed via whole-genome shotgun sequencing (Illumina NovaSeq/HiSeq).ResultsCo-infected patients exhibited significantly elevated plasma LPS (78.09 vs 48.72 pg/mL, p=0.032) and sCD14 (2667 vs 1927 ng/mL, p=0.0015) compared to controls. Although no differences in α-diversity or overall taxonomic abundance were observed between the PC and NC groups, 329 PC-unique and 216 NC-unique microbial species were identified. Nine genera demonstrated diagnostic potential for co-infection [Area Under the Curve (AUC), >0.7] with Akkermansia showing the highest predictive value (AUC = 0.811). Critically, Blautia abundance was significantly reduced in severe-to-critical cases (PC2) versus mild-moderate cases (PC1, p=0.043) and controls (NC, p=0.006). Besides, our function prediction for gut microbiota suggested that SARS-CoV-2 may exacerbate lipid metabolic dysregulation in HIV-infected individuals.ConclusionsHIV/SARS-CoV-2 co-infection is characterized by heightened microbial translocation and species-specific microbiota alterations rather than global dysbiosis. Blautia depletion may correlate with COVID-19 severity.

Background The ‘Shock and Kill’ strategy is pivotal in the quest for an HIV/AIDS cure. Our study explores Euphorbia kansui (Kansui), a traditional Chinese medicine, for its potential to reverse HIV latency while rigorously assessing safety. Methods We conducted a phase 1b/2a clinical trial at the Shanghai Public Health Clinical Center (NCT04503928). People with HIV (PWH) on ART were assigned to three groups: 1 g qd (once per day) for 7 days, 1g bid (twice per day) for 7 days, or 1 g qd for 14 days. Blood was collected on Days 0, 1, 3, 5, 7, 14, and 21. Primary en dpoints included changes from baseline in cell-associated (CA) HIV RNA and plasma HIV viral load, while secondary endpoints involved integrated HIV DNA levels and safety assessments. Results Nine PWHs male participants (mean age: 38.78±13.85 years old) with a median antiviral treatment duration of 49 months, were enrolled in the clinical study. HIV latency reversal was primarily observed within the first seven days following Kansui administration. A ≥2-fold increase in cell-associated (CA) HIV RNA was detected in four participants, three of whom received the 1 g qd dose. Additionally, two participants exhibited a transient increase in plasma HIV RNA to >50 copies/mL, with one case in the 1 g qd for 7 days group and the other in the 1 g qd for 14 days group. Integrated HIV DNA levels transiently increased during the intervention and then quickly returned to baseline levels without significant decline. Kansui demonstrated a favorable safety profile, with no serious adverse events reported and only mild adverse events observed. Conclusion Kansui can reactivate latent HIV viral reservoirs at a low-level in vivo and is well tolerated by PWH on antiretroviral therapy which warrant further investigation.

OBJECTIVES:To evaluate the association between immune status and subclinical myocardial injury by cardiovascular magnetic resonance (CMR) in people with HIV (PWH), independent of traditional cardiovascular risk factors. DESIGN:This prospective study enrolled 98 PWH without known cardiovascular disease (CVD) and 91 Framingham Risk Score (FRS)-matched non-HIV controls. METHODS:Myocardial function and tissue characteristics were assessed by CMR, including native T1/T2 mapping, extracellular volume fraction (ECV), and late gadolinium enhancement (LGE). Immunologic and treatment-related variables included duration of HIV infection, duration of ART, HIV viral load, current and nadir CD4 + and CD8 + T-cell counts, and CD4/CD8 ratio. Linear and logistic regression analyses adjusted for FRS and heart rate evaluated associations between immunologic parameters and CMR findings. RESULTS:PWH demonstrated elevated global native T1, T2, ECV, and LGE, with reduced global longitudinal strain (GLS) and global circumferential strain (GCS) compared with non-HIV controls (all P  < 0.05). In multivariate analysis, current CD4 + T-cell counts correlated negatively with global native T1 ( β  = -0.361, P  < 0.001) and ECV ( β  = -0.318, P  = 0.001). Current CD4 + cell count <200 cells/μl was independently associated with elevated native T1 [odds ratio (OR), 7.199; 95% confidence interval (CI), 1.373-37.746; P  = 0.020] and elevated ECV (OR, 5.152; 95% CI, 1.260-21.062; P  = 0.023). CONCLUSION:PWH exhibit subclinical myocardial fibrosis and dysfunction despite similar FRS to non-HIV controls. Current CD4 + T-cell counts <200 cells/μl is an independent predictor of subclinical myocardial injury.

BACKGROUND:Dolutegravir (DTG), a cornerstone of human immunodeficiency virus-1 (HIV-1) treatment, is primarily metabolized by UDP-glucuronosyltransferase 1A1 (UGT1A1). Polymorphisms in the UGT1A1 gene have been shown to influence the pharmacokinetics of DTG across different ethnic populations. This study aims to characterize the distribution of UGT1A1 polymorphic alleles and evaluate their impact on DTG plasma trough concentrations in Han Chinese individuals living with HIV-1 infection. METHODS:This study enrolled Han Chinese adults from the Outpatient Department of Infection and Immunity, Shanghai Public Health Clinical Center, between September 2 and November 2, 2024, who were infected with HIV-1 and had been receiving DTG treatment for at least 10 days. Seven segments of the UGT1A1 gene, including exons 1-5, the promoter TATA box, and the phenobarbital-responsive enhancer module (PBREM), were amplified to identify potential polymorphisms. The association between these gene polymorphisms and DTG plasma trough concentrations was investigated. RESULTS:A total of 287 Han Chinese with HIV-1 infection were included in the study, of which 96.2% (276/287) were male, with a median age of 40 years (interquartile range [IQR]: 32-51 years). The median trough concentration of DTG was 2427 ng/mL (IQR: 1807-3107 ng/mL). The three most common alleles identified were (1) 211G>A in exon 1 (UGT1A1*6, rs4148323), (2) seven TA repeats in TATA box (UGT1A1*28, rs3064744), and (3) -3279T>G in PBREM (UGT1A1*60, rs4124874). The percentages of heterozygotes for these alleles were 31.7%, 22.0%, and 49.1%, respectively, while the frequencies of homozygotes were 4.2%, 1.4%, and 8.0%, respectively. Plasma trough concentrations of DTG were significantly higher in patients carrying one or two alleles of UGT1A1*6 compared to those with the wild-type genotype (P <0.001). However, neither UGT1A1*28 nor UGT1A1*60 alone significantly affected DTG trough concentrations. Multiple linear regression analysis revealed that low body weight, the presence of one or two UGT1A1*6 alleles, and compound heterozygote of UGT1A1*6/*60 or UGT1A1*6/*28/*60 were independent risk factors associated with high DTG plasma trough concentrations. CONCLUSIONS:The frequencies of heterozygotes for UGT1A1*6, UGT1A1*28, and UGT1A1*60 were found to be high in the studied population. In addition to low body weight, the presence of UGT1A1*6 and compound heterozygosity of UGT1A1*6/*60 or UGT1A1*6/*28/*60 were significant factors contributing to elevated DTG trough concentrations.

e16258 Background: Although hepatectomy offers a potential cure for HCC, postoperative recurrence remains high and adversely impacts long-term survival. Currently, no standard adjuvant therapy has been established for patients at high risk of recurrence. This study evaluated the efficacy and safety of adjuvant donafenib with or without transarterial chemoembolization (TACE) in this population. Methods: We retrospectively analyzed clinicopathological data from HCC patients with high recurrence risk after radical resection at Nantong Third People’s Hospital, between March 2023 and November 2025. High risk was defined as meeting at least two of the following criteria: tumor diameter > 5 cm; multiple tumors; microvascular invasion (MVI) positive; Edmondson–Steiner grade Ⅲ–Ⅳ; postoperative alpha-fetoprotein (AFP) at the first month ≥10 μg/L; or postoperative des-gamma-carboxy prothrombin (DCP) at the first month > 32 mAU/mL. Patients received adjuvant donafenib alone or combined with one session of TACE; the TACE procedure was performed within the first postoperative month. Recurrence-free survival (RFS), overall survival (OS), and safety (assessed per CTCAE v5.0) were analyzed. Results: At data cutoff (December 2025), 37 patients were included with a median age of 64.4 years (SD: 9.0), most were male (73.0%), and had HBV infection (89.2%). All patients with Child-Pugh A liver function and ECOG PS 0. High-risk features included: tumor > 5 cm (29.7%), multiple lesions (37.8%), MVI-positive (73.0%), Edmondson-Steiner grade Ⅲ (89.2%), postoperative AFP≥10 μg/L (18.9%), and postoperative DCP > 32 mAU/mL (32.4%). Treatment distribution included donafenib monotherapy (n = 19) and donafenib plus TACE (n = 18). For the overall population, median RFS and OS were not reached, and the 1-year RFS rate was 76.4% (95% CI: 59.8–97.8%); the 2-year RFS rate was 67.9% (95% CI: 48.5–95.2%). Subgroup analyses were performed based on treatment, biomarker levels, and pathological features. The 1-year RFS was 81.2% for donafenib alone and 73.3% for donafenib plus TACE. According to postoperative AFP levels, the 1-year RFS was 57.1% in patients with AFP≥10 μg/L and 81.3% in those with AFP < 10 μg/L. By MVI status, the rate was 100.0% in MVI-negative patients and 71.1% in MVI-positive patients. According to Edmondson–Steiner grade, the 1-year RFS was 100.0% for grade Ⅱ and 74.9% for grade Ⅲ. Treatment-related adverse events (TRAEs) occurred in 7 patients (18.9%), all grade 1–2; no grade ≥3 TRAEs were observed. Conclusions: In this retrospective analysis, adjuvant donafenib with or without TACE demonstrated promising recurrence-free survival with a favorable safety profile in HCC patients at high risk of recurrence after radical resection. These results support further investigation in prospective studies.

Background People living with HIV (PWH) are at increased risk of cardiovascular disease; however, evidence from Asian populations remains limited. We evaluated the prevalence and characteristics of carotid plaques among PWH and people without HIV (PWoH) in China to examine the impact of HIV infection on subclinical atherosclerosis.Methods In this cross-sectional study conducted at the Shanghai Public Health Clinical Center, China, we enrolled 1390 PWH and 1390 age-frequency and sex-frequency matched PWoH aged 40 years or older. Carotid ultrasonography was used to assess the presence, number and echogenicity of carotid plaques.Results The prevalence of carotid plaques was significantly higher in PWH than in PWoH (45.3% vs 37.5%, p<0.001), and the prevalence of echo-lucent plaques was also higher (21.1% vs 18.0%, p=0.045). Among participants with carotid plaques, PWH were more likely to have three or more plaques (35.8% vs 21.2%, p<0.001) and a greater maximum plaque thickness (2.0 mm vs 1.9 mm; p=0.026). After adjustment for age, sex and dyslipidaemia, HIV infection remained independently associated with increased odds of carotid plaques (adjusted OR (aOR)=1.45; 95% CI 1.23 to 1.70) and echo-lucent plaques (aOR=1.24; 95% CI 1.02 to 1.50). Associations were strongest among men and younger participants. No HIV-related clinical factors were significantly associated with carotid plaque presence.Conclusion HIV infection is independently associated with an increased carotid plaque burden and echo-lucent plaque features, suggesting accelerated atherosclerosis beyond traditional risk factors. These findings support routine cardiovascular risk assessment and early preventive strategies in PWH.

Identifying patients at highest risk of serious adverse prognostic events (AE) in neurosyphilis could enable risk-stratified treatment beyond clinical judgment. We developed machine-learning models using electronic health records from six Chinese infectious-diseases hospitals, with two centers for external validation and four for discovery. Five models incorporated demographic, clinical, laboratory, and treatment variables from 602 observations (402 discovery, 200 validation). AE occurred in 20.90% and 20.50%, respectively. DEFEAT-NS-M1 achieved AUROC 0.975 (95% CI 0.949-0.995) internally and 0.863 (0.801-0.920) externally, with Brier scores 0.027 and 0.128. Decision curve analysis demonstrated favorable clinical utility; treating 1-2 high-risk patients prevents one AE. DEFEAT-NS-M1 supports population-level risk estimation and stratified care, potentially guiding targeted monitoring and therapy. Further external validation and health-economic assessment are warranted.

BACKGROUND:Short-term variation in the Fibrosis-4 index (FIB-4) may identify people who warrant further liver assessment. We evaluated longitudinal FIB-4 changes and associated metabolic factors in people with HIV (PWH) and metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS:This retrospective cohort included 683 PWH with ultrasound-defined MASLD who underwent routine clinical and laboratory assessments approximately every three months. A prespecified FIB-4 increase required both a ≥20% rise and crossing to ≥1.3 among participants with baseline FIB-4 < 1.3, or a ≥20% rise among those with baseline FIB-4 ≥ 1.3. RESULTS:Of 683 enrolled participants, 655 were analyzed longitudinally. Over a median follow-up of 12.0 months, 59 (9.0%) met the FIB-4 increase definition, corresponding to 8.8 events per 100 person-years. Weight gain was associated with this outcome (adjusted hazard ratio 1.19 per 1% increase, 95% CI 1.14-1.24), whereas HIV- and antiretroviral therapy-related variables were not. Transition from non-obesity to obesity was associated with the outcome (odds ratio 8.45, 95% CI 3.57-20.02). Weight change also correlated with concurrent changes in total cholesterol, triglycerides, fasting glucose, and liver enzymes (all p < 0.01). CONCLUSIONS:Weight gain was associated with short-term FIB-4 increase and with concurrent metabolic change in PWH with MASLD.

Liver fibrosis is a common response to chronic liver injury due to multiple etiologies and plays a crucial in the progression of chronic liver disease to cirrhosis, hepatocellular carcinoma, and other liver-related clinical outcomes. Currently, available treatments to block liver fibrosis are designed to eliminate the underlying causes of liver disease. The lack of truly effective drugs to regress or reverse fibrosis is a major unmet clinical need. In this context, this article briefly describes the pathological process of hepatic fibrosis and focuses on reviewing the progress of clinical studies on mechanism-based anti-fibrotic drug development and therapy, highlighting that the positive effect of thyroid hormone receptor-β (THR-β) analogs, fibroblast growth factor 21 (FGF21) analogues, Glucagon-like peptide 1 receptor (GLP-1R) agonists, pan-peroxisome proliferator-activated receptor (pan-PPAR) agonists, fatty acid synthase (FASN) inhibitors, and hydronidone in reducing liver fibrosis caused by specific etiologies. Moreover, multi-pathway guided combination therapy or traditional Chinese medicine demonstrate significant advantages in combating liver fibrosis. Finally, new technologies and approaches affecting the clinical development of anti-hepatic fibrosis drugs were discussed.

The underlying mechanisms and diagnostic biomarkers for the progress of COVID-19 in HIV patients have not been fully elucidated. In this study, the aim is to analyze the metabolomic profiles of HIV/AIDS patients co-infected with SARS-CoV-2 and to identify biomarkers indicative of co-infection. In this study, we conducted a retrospective cohort analysis of peripheral blood samples collected from 30 HIV/AIDS patients co-infected with SARS-CoV-2 (pc group) and 30 patients without SARS-CoV-2 (nc group). In this study, through non-targeted metabolomics and lipidomics analysis, 77 differential metabolites were identified in the plasma of patients co-infected with HIV and SARS-CoV-2 compared to the nc group, with vitamin K1 emerging as a significant feature. Moreover, the plasma of the pc group showed disturbances in lipid metabolism, with elevated triglycerides (TG) and phosphatidylcholine (PC) and decreased phosphatidylglycerol (PG) compared to the control group. Vitamin K1 may be a biomarker for SARS-CoV-2 in HIV/AIDS patients, and changes in the levels of TG, PC, and PG molecules appear to be the main features following HIV co-infection with COVID-19. The emphasis in our study is on the power of using comprehensive metabolomics (lipidomics) approaches to identify metabolic biomarkers and potential mechanisms of COVID-19 in HIV/AIDS patients.