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Background Previous studies have indicated a strong association between CD169 and HIV-1 infection, showing significant elevation of CD169 during infection and viral replication. This study aimed to investigate whether CD169 could serve as a biomarker for the early diagnosis of HIV-1 infection. Methods We recruited patients with acute people with HIV(PWH), ART-treated PWH and HIV-1 negative volunteers. Clinical data and peripheral blood samples were collected. CD169 expression on CD14 + monocytes was detected by flow cytometry, and soluble CD169 in plasma was assayed to investigate its relationship with HIV-1 infection and disease progression. Results Our study detected a high proportion of CD169 + CD14 + monocytes in individuals with acute PWH. Furthermore, we observed that CD169 expression levels were elevated in PWH who had stopped taking their medication. Conclusion The discovery of CD169 expression in CD14 + monocytes as a biomarker for early HIV-1 infection or AIDS diagnosis offers new possibilities for early intervention and treatment, potentially improving clinical outcomes for PWH. Clinical Trial Not applicable.

This study aimed to investigate the influencing factors of delayed clearance of Talaromyces marneffei (T. marneffei) in blood culture of patients with acquired immune deficiency syndrome (AIDS) complicated with talaromycosis after antifungal therapy. The patients with AIDS complicated with talaromycosis were retrospectively enrolled, and divided into two groups according to the blood T. marneffei culture results in two weeks after antifungal therapy. The baseline clinical data were collected and the antifungal susceptibility of T. marneffei was tested. A total of 190 patients with AIDS and talaromycosis were enrolled, of whom 101 cases remained positive for T. marneffei (Pos-group) while the other 89 cases were negative in blood culture (Neg-group) after two weeks' antifungal treatment. The Pos-group had a higher baseline Aspartate aminotransferase (AST, 78.5 vs. 105 U/L; P = 0.073) and lower CD4+ T cells level (11 vs. 7 cells/μl; P = 0.061). The percentage of isolates with higher MICs of voriconazole (VOR) and fluconazole (FLU) in the Pos-group were significantly higher than those in the Neg-group (χ2 = 12.623, P < 0.001 and χ2 = 9.356, P = 0.002, respectively). By multivariate logistic regression, the MIC value for VOR was identified as the prognostic variable that may influence the clearance of T. marneffei in blood culture after antifungal therapy among AIDS patients with talaromycosis. The delayed negative conversion of blood T. marneffei-culture may be associated with some factors especially higher MIC of VOR, indicating the possibility of drug resistance of T. marneffei.

Abstract Background: Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China. Methods: Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses. Results: A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4+ T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48-5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P <0.01). Conclusions: Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.

Background Talaromycosis marneffei (TSM) is one of the leading causes of death among patients with acquired immunodeficiency syndrome (AIDS). Currently, culture-based testing methods for TSM take 3 to 7 days, leading to diagnostic delays. Early and accurate methods are urgently needed to enhances prognosis. This study aimed to develop and validate two clinical diagnostic models for the early and rapid identification of Talaromycosis marneffei (TSM) among AIDS inpatients within 48 h. Method We included 600 AIDS inpatients with or without TSM, who were randomly assigned to a training cohort ( N  = 420) and an internal test cohort ( N  = 180). An additional 180 patients were enrolled as a temporal testing cohort. LASSO and logistic regression (LR) analyses were conducted to identify and test potential predictors for TSM in AIDS inpatients. Results Eight variables (rash, lymphadenopathy or hepatosplenomegaly, CD4 + T cell counts, adenosine deaminase levels, aspartate aminotransferase levels, white blood cell counts, procalcitonin levels, and galactomannan [GM] levels), which can be obtained from 24 to 48 h, were identified as significant predictors of TSM. Then a Basic model was established using the most basic clinical symptoms and biochemical markers, and a GM model was constructed by incorporating GM testing into the Basic model. Both models exhibited excellent discrimination ability with an area under the curve (AUC) of 0.88 (95% CI: 0.85–0.91) and 0.93(95% CI: 0.90–0.95) in the training cohort respectively. In the internal test cohort, the Basic model and the GM model yielded AUCs of 0.88 (95% CI: 0.83–0.93) and 0.92 (95% CI: 0.87–0.96), respectively. In the temporal test cohort, the Basic model and the GM model yielded an AUC of 0.81 (95% CI: 0.75–0.87) and 0.86 (95% CI: 0.80–0.92), respectively. Moreover, the Basic model demonstrated sensitivity and specificity comparable to those of previous models according to the DeLong test. The GM model outperformed the Basic model as well as the Mp1p and GM tests, with AUC, sensitivity, and specificity (p-values < 0.01). Conclusions This study successfully established and tested two TSM clinical diagnostic models suitable for regions with different levels of healthcare resources. The basic model has broader applicability and is suitable for environments with relatively limited medical resources. It can effectively improve the diagnostic performance for TSM in underdeveloped healthcare regions. Adding GM testing to the basic model enhances the diagnostic efficacy, offering a straightforward, practical, and quantitative approach for healthcare institutions capable of detecting GM.

Talaromycosis is a life-threatening fungal disease commonly seen in patients with acquired immunodeficiency syndrome (AIDS), which is endemic in Southern China and Southeast countries. The diagnostic methods available for talaromycosis are relatively time-consuming and yield a high mortality. Therefore, early diagnosis of talaromycosis is extremely important. We aimed to determine a potential method for assisting in its early diagnosis. A total of 283 patients with AIDS admitted to our hospital were prospectively included in this cross-sectional study and divided into those with Talaromyces marneffei (TSM group, n = 93) and those without Talaromyces marneffei (non-TSM group, n = 190). The diagnostic accuracy of the Mp1p enzyme immunoassay (EIA), galactomannan (GM) assay, and blood culture performed within 3 days of hospitalisation were evaluated, using talaromycosis confirmed by culture and/or pathology as the gold standard. The positivity rates in the Mp1p EIA, GM assay, and blood culture were 72%, 64.5%, and 81.7%, respectively, in the TSM group. The sensitivity, specificity, and positive and negative predictive values of the Mp1p EIA were 72.0% (67/93), 96.8% (184/190), 91.8% (67/73), and 87.6% (184/210), respectively. The Mp1p EIA showed a substantial agreement with the gold standard (kappa: 0.729) and superiority to the GM assay (kappa: 0.603); it also showed a superior diagnostic accuracy in the patients with CD4+ counts of < 50 cells/µL compared to those with CD4+ counts ranged from 50–100 cells/µL. The Mp1p EIA has the advantage of assisting in the early diagnosis of talaromycosis in patients with AIDS, especially those with low CD4+ counts.

The persistence of latent HIV-1 reservoirs remains a critical barrier to functional curing AIDS, as current latency-reversing agents (LRAs) exhibit limited clinical efficacy. While RNA modifications like N⁶-methyladenosine (m⁶A) regulate viral replication, their role in maintaining HIV-1 latency is poorly defined. Here, we identify the RNA-binding protein RBM39 as a scaffold organizing an m⁶A-dependent silencing complex that enforces viral latency. Through proteomic and functional analyses, we demonstrate that RBM39 recruits the m⁶A reader YTHDC1 and the RNA helicase DDX5, forming a tripartite complex that accelerates Tat RNA decay and enforces viral quiescence. Genetic or pharmacological degradation of RBM39 (using the clinically explored molecular glue indisulam ) potently reactivates latent HIV-1 in J-Lat cell models, primary CD4⁺ T cells from people living with HIV-1 (PLWH), and synergizes with established LRAs (Bryostatin-1, JQ-1, SAHA) to broadly activate proviral reservoirs. Our work reveals a previously unrecognized host pathway in which RBM39-organized RNA decay complexes silence HIV-1 through epitranscriptomic regulation of Tat. In addition to establishing RBM39 as a promising therapeutic target for addressing the limitations of current “shock and kill” strategies, our findings establish a novel mechanistic framework for m⁶A-dependent regulation of viral gene expression. This framework may serve as a valuable reference for investigating similar regulatory mechanisms in other latent viral infections or oncogenic processes where RNA methylation plays a pivotal role.

HIV-associated talaromycosis causes substantial mortality despite available therapies. Early identification of high-risk patients remains challenging, particularly in resource-limited settings. We aimed to develop and validate a dynamic prognostic model for rapid risk stratification. This retrospective cohort study analyzed 1,892 HIV-talaromycosis patients admitted to Guangzhou Eighth People's Hospital (2011-2023). Poor outcome (in-hospital death or deterioration-related discharge) was the primary endpoint. A nomogram was developed using Cox regression on admission variables in a training set (2011-2020, N = 1,435), with internal validation set (2011-2020, N = 431) and independent testing set (2021-2023, N = 457). Performance was assessed via time-dependent AUC, C-index, calibration, and decision curve analysis. Poor outcomes occurred in 14.1% of cases (266/1,892), with 86.5% of these events happening within 28 days. Winter admissions exhibited the lowest case volume but the highest poor outcome rate. Multivariable analysis revealed eight independent readily available predictors: absence of lymphadenopathy (aHR: 0.581, 95%CI: 0.396-0.852, P = 0.005) and hepatosplenomegaly (aHR: 0.347, 95%CI: 0.232-0.519, P < 0.001), respiratory rate (aHR: 1.041, 95%CI: 1.007-1.076, P = 0.016), white blood cell count (aHR: 1.089, 95%CI: 1.049-1.132, P < 0.001), platelet count (aHR: 0.995, 95%CI: 0.992-0.997, P < 0.001), albumin level (aHR: 0.911, 95%CI: 0.872-0.952, P < 0.001), lactate dehydrogenase (aHR: 1.000, 95%CI: 1.000-1.000, P < 0.001), and blood urea nitrogen (aHR: 1.087, 95%CI: 1.068-1.106, P < 0.001). The above indicators were stratified according to predefined classifications and used to established a nomogram. The nomogram demonstrated strong discriminatory performance for 7-, 14-, and 28-day outcomes (AUC 0.905/0.863/0.838 in development; 0.851/0.832/0.807 in independent testing; C-index 0.813-0.841). Calibration curve analysis demonstrated that the nomogram exhibited excellent predictive accuracy and decision curve analysis indicated substantial clinical benefit. The model could effectively differentiate between high-risk and low-risk populations. This study provides a dynamically validated prognostic tool for HIV-associated talaromycosis, enabling risk stratification using readily available clinical data. Its integration into electronic health systems could off an opportunity to optimize resource allocation and improve outcomes in endemic regions.

Talaromycosis is one of the most common opportunistic infections in human immunodeficiency virus (HIV) infected patients. However, few researches have explored the prevalence in Southern China and fully assessed the value of the Mp1p antigen screening for the diagnosis of talaromycosis. We performed a cross-sectional study of HIV-infected antiretroviral therapy (ART)-naïve adult patients who were seen in 2018 at Guangzhou Eighth People's Hospital, Guangzhou Medical University. Serum samples collected from all the 784 enrolled patients were tested for Mp1p antigen using double-antibody sandwich enzyme-linked immunosorbent assay. A culture of pathogen was conducted in 350 clinically suspected patients to confirm talaromycosis. The overall prevalence of talaromycosis based on the Mp1p antigen detection was 11.4% (89/784) and peaked at 32.2% (75/233) in patients with CD4+ ≤50 Nr/μl. Logistic regression analysis found Mp1p antigen positive rate decreased with the increase in CD4+ counts (OR 0.982, 95% CI 0.977-0.987, P<0.01). The optimal cut-off point of the CD4+ count was 50 Nr/μl or less. Among the 350 patients received both fungal culture and Mp1p antigen detection, 95/350 (27.1%) patients were culture-positive for a Talaromyces marneffei, 75/350 (21.4%) patients were Mp1p antigen positive. The Mp1p antigen assay showed a good agreement to the culture of pathogen, and the sensitivity, specificity, positive predictive value, negative predictive value and kappa value was 71.6% (68/95), 97.3% (248/255), 90.7% (68/75), 90.2% (248/275), and 0.737, respectively. The screening accuracy of the Mp1p antigen assay in patients with CD4+ counts of ≤50 Nr/μl was superior to that in those with higher CD4+ counts. Mp1p antigen screening can be an effective tool for more efficient diagnosis of Talaromycosis, especially in HIV/AIDS patients with low CD4+ counts. Future validation studies are needed.