Search Results (126)

Co-infections pose significant challenges not only clinically, but also in terms of simultaneous diagnoses. The development of sensitive, multiplexed analytical platforms is critical for accurately detecting viral co-infections, particularly in complex biological environments. In this study, we present a mass spectrometry (MS)-based detection strategy employing a target-triggered hybridization chain reaction (HCR) to amplify signals and in situ photocleavable mass tags (PMTs) for the simultaneous detection of multiple targets. Hairpin DNAs modified with PMTs and immobilized loop structures on magnetic particles (Loop@MPs) were engineered for each target, and their hybridization and amplification efficiency was validated using native polyacrylamide gel electrophoresis (PAGE) and laser desorption/ionization MS (LDI-MS), with silica@gold core–shell hybrid (SiAu) nanoparticles being employed as an internal standard to ensure quantitative reliability. The system exhibited excellent sensitivity, with a detection limit of 415.12 amol for the hepatitis B virus (HBV) target and a dynamic range spanning from 1 fmol to 100 pmol. Quantitative analysis in fetal bovine serum confirmed high accuracy and precision, even under low-abundance conditions. Moreover, the system successfully and simultaneously detected multiple targets, i.e., HBV, human immunodeficiency virus (HIV), and hepatitis C virus (HCV), mixed in various ratios, demonstrating clear PMT signals for each. These findings establish our approach as a robust and reliable platform for ultrasensitive multiplexed detection, with strong potential for clinical and biomedical research. Full article

Coinfections with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) among individuals with chronic hepatitis B (CHB) are associated with worse clinical outcomes but remain understudied due to their low prevalence and the sensitivity of associated data. This nationwide, cross-sectional study utilized claims data from the Korean Health Insurance Review and Assessment Service (2014–2021) to investigate the prevalence, comorbidities, treatment patterns, and liver-related complications among patients with HBV monoinfection, HBV/HIV, HBV/HCV, or triple coinfection. Among over 4.5 million patients with chronic hepatitis B, the prevalence of HIV and HCV coinfection ranged from 0.05 to 0.07% and 0.77 to 1.00%, respectively. Patients with HBV/HCV coinfection were older and had significantly higher rates of hypertension, diabetes, dyslipidemia, and major adverse liver outcomes, including hepatocellular carcinoma and liver transplantation, compared to other groups. HBV/HIV coinfection was more common in younger males and was associated with higher dyslipidemia. The use of HBV antivirals increased over time across all groups. These findings highlight the distinct clinical characteristics and unmet needs of coinfected populations, underscoring the importance of tailored screening and management strategies in HBV-endemic settings. Full article

Psoriasis, a chronic immune-mediated inflammatory skin disorder, presents complex pathogenetic mechanisms potentially influenced by viral infections. This comprehensive study explored the possible interplay of resistance and viral infections among psoriasis patients using serological screening techniques. The investigation involved 90 patients aged 23–45 years, systematically examining viral seropositivity for HSV (herpes simplex virus), HZ (herpes zoster), HBV (hepatitis B virus), HIV (human immunodeficiency virus), and HCV (hepatitis C virus) through ELISA testing. The findings revealed notable active or recent viral infection rates: 8.9% HSV positivity, 2.2% HZ antibody detection, 4.4% HCV positivity, and 4.4% HIV positivity. The research can contribute to current knowledge gaps, broaden the knowledge regarding the relationship between psoriasis and viral infection, and assess resistance, as it can mediate the interaction. The results can lead to improved diagnosis, treatment, and patient care options. This study emphasizes the importance of thorough viral testing for psoriasis patients, as well as focused therapeutic regimens that take into account viral co-infections. It elucidates the complex networks of biological relationships between immune factors, contributes information that is critical to our understanding of the multifactorial etiology of psoriasis, and concludes with a strong argument for investigating the mechanisms of viral involvement in this chronic-relapsing inflammatory disease. Full article

In HCV-coinfected people with HIV (PWH), there are still conflicting data regarding the long-term metabolic impact of HCV eradication. The aim of the study is to investigate long-term changes in controlled attenuation parameter (CAP) and metabolic profile after sustained virological response (SVR) post-direct acting antivirals (DAAs) in PWH. This is a retrospective observational study including individuals with HIV/HCV coinfection, followed as outpatients at San Raffaele Hospital, who achieved SVR post-DAAs. Individuals were assessed for metabolic parameters before and after the start of DAAs. Univariate and multivariate mixed linear models were calculated to estimate crude mean changes in CAP, metabolic parameters, and weight; slopes were reported with the corresponding 95% confidence intervals (95% CI). Overall, during a median follow-up of 4.02 years (interquartile range, IQR 3.04–4.80), the mean percent increase in CAP was 2.86/year (p < 0. 0001), and the mean decrease in stiffness was –4.28 (p = 0.003). Additionally, total cholesterol (p < 0.0001), high-density lipoprotein (HDL) cholesterol (p = 0.001), triglycerides (p < 0.0001), glucose (p < 0.0001), and Body Mass Index (BMI) (p < 0.0001) increased over time. A long-term follow-up in PWH with SVR post-DAAs showed an overall significant increase in CAP and worsening of the metabolic profile, suggesting a higher risk of developing liver steatosis and metabolic alterations over time. Full article

Background/Objectives: This study aimed to explore how HTLV-2 infection affects the production of broadly neutralizing antibodies (bNAbs) in persons with HIV-1 (PWH) and to assess the impact of boosted protease inhibitors (PIs). Methods: We evaluated broadly neutralizing antibody (bNAb) activity in 65 PWH, which included 27 who were also co-infected with HTLV-2. All participants were former injection drug users with HCV antibodies and were receiving suppressive antiretroviral therapy (ART). Neutralizing activity was assessed against six recombinant HIV-1 viruses that represent five different subtypes. B cell subsets were also analyzed. Results: HTLV-2 co-infection and the lack of ritonavir-boosted protease inhibitors (r-PIs) were both independently associated with higher neutralization scores (p = 0.017 and p = 0.005, respectively). Among those not on r-PIs, individuals co-infected with HTLV-2 showed significantly higher neutralization scores (p = 0.027) and a broader neutralization breadth (83.4% vs. 48.5%, p = 0.015) compared to those infected only with HIV-1. Additionally, HTLV-2 co-infected individuals had more resting memory B cells (p = 0.001) and fewer activated memory B cells (p = 0.017) than the HIV-1 mono-infected individuals. In our multivariate analysis, only HTLV-2 co-infection remained independently associated with neutralization scores (p = 0.027). Elite neutralizers (with a breadth score of ≥10) had more naive B cells and fewer resting memory B cells compared to those with weaker neutralization in both groups. Conclusions: Co-infection with HTLV-2 enhances bNAb production in PWH on suppressive ART and, in particular, in the absence of r-PI regimens. The prominent neutralizing activity corresponded with B cell subset distributions. The results suggest the complexity regarding the interaction between viral co-infections, antiretroviral regimens, and humoral immune compartments and may inform further H1V-1 pathogenesis inquiries or the appropriate design of a vaccine. Full article

Background: Anti-HIV neutralizing antibodies (anti-HIV-nAbs) play a critical role in the immune defense against HIV by preventing viral entry and limiting replication. This study longitudinally evaluated the titers and variability of anti-HIV-nAbs in individuals coinfected with HIV and HCV. Samples were collected at three time points: before starting HCV treatment, one year after completion, and five years post-treatment. Methods: A retrospective analysis was conducted on 71 HIV/HCV-coinfected patients who achieved a sustained virologic response following antiviral therapy for HCV. A control group of 41 HIV-monoinfected individuals was also included. Anti-HIV-nAb titers were evaluated by HIV neutralization assays using a panel of six recombinant HIV viruses representing multiple genetic subtypes. Generalized Linear Mixed Models and Generalized Linear Models were used for statistical analysis. p-values were adjusted using the Benjamini–Hochberg procedure (q-value). Results: HIV-neutralizing antibody responses in HIV/HCV-coinfected individuals remained stable over five years following HCV therapy without significant changes (q-value > 0.05). The mean neutralization scores remained stable, with baseline scores of 6.1 (95% CI: 5.4–6.7), 6.2 (95% CI: 5.5–6.8) at one year post-HCV therapy, and 6.0 (95% CI: 5.3–6.7) at five years post-HCV therapy. HIV/HCV-coinfected individuals consistently showed lower neutralization scores compared to the control group throughout the follow-up (q-value < 0.05). Regression analyses adjusted for age, gender, nadir CD4⁺, and baseline CD4⁺ counts confirmed that the observed differences between HIV-monoinfected and HIV/HCV-coinfected individuals persisted (q-value < 0.05) at both the baseline and after HCV therapy completion. Conclusions: Successful HCV eradication in HIV/HCV-coinfected individuals did not normalize anti-HIV-nAb titers, which remained consistently lower than those in HIV-monoinfected controls over five years. Full article

Background: Hepatitis B (HBV) and C (HCV) virus coinfections remain major contributors to liver-related morbidity and mortality among people living with HIV (PLWH). This study aimed to assess the prevalence of HBV and/or HCV coinfections in a Romanian HIV cohort and to evaluate their impact on immunological, virological, and liver function parameters under antiretroviral therapy (ART). Methods: We retrospectively analyzed 462 HIV-infected patients (2018–2021) from the National Institute of Infectious Diseases, Bucharest, stratified into four groups: HIV mono-infection (n = 176), HIV/HBV (n = 114), HIV/HCV (n = 97), and HIV/HBV/HCV (n = 75) coinfections. Immunological (CD4 count, CD8 count, and CD4/CD8 ratio), virological (HIV-1 RNA), and hepatic parameters (ALT, AST, GGT, bilirubin, amylase, and lipase) were compared. Results: No significant differences were observed between groups regarding the immune recovery (mean CD4 count p = 0.89, HIV-RNA suppression p = 0.78). However, liver and pancreatic parameters showed statistically significant deterioration in the coinfected groups. ALT (p < 0.001), GGT (p = 0.009), total bilirubin (p = 0.011), amylase (p = 0.010), and lipase (p < 0.001) were significantly higher in the triple-infection (HIV/HBV/HCV) group compared to HIV mono-infected patients. Coinfection was also associated with a longer duration of illness (p = 0.002) and therapy (p = 0.021) and with a higher number of ART regimens used (p = 0.013). Conclusions: While HIV suppression and immune recovery were not significantly impaired by HBV/HCV coinfections, liver and pancreatic injuries were significantly more prevalent and severe in coinfected patients. Regular monitoring of hepatic function and integrated management strategies are recommended to minimize liver-related complications in this population. Full article

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality. HCC is characterized by high heterogeneity and, subsequently, adaptation by developing resistance to current treatments. Applying individualized models is crucial to understanding the potential of approved therapies. Therefore, we classify a primary-like cell line derived from the core region of an HCC with underlying HIV-HCV co-infection employing deep analysis on the pathway regulation level. Methods: We employed DEG analysis, followed by pathway analysis, to characterize the preservation level of the LC4 cells and the level of adoption. Next, we classify the new model for HCC research by employing healthy donor samples, commonly used HCC cell lines, and global RNAseq datasets. Results: LC4 cells reflect the characteristics of the parental cancer region, including immunosuppression and metabolic reprogramming, characterized by the downregulation of drug-metabolizing enzymes compared to healthy individuals, indicating a transition to alternate metabolic pathways. Moreover, we identified specific biomarkers equally regulated in the parental tissue, in global datasets of the same entities as well as in LC4 cells. Conclusions: We classified LC4 cells as an individual immunosuppressive and highly progressive primary-like HCC cell line. LC4 cells are applicable as a model for preclinical drug testing, minimizing the lack of preclinical models in HCV-HIV-induced HCC research. Full article

This study aimed to assess the prevalence of HDV (hepatitis delta virus), HCV (hepatitis C virus), and HIV (human immunodeficiency virus) coinfections among HBsAg-positive patients and to determine the severity of liver fibrosis and biochemical markers. Furthermore, the study sought to evaluate the noninvasive fibrosis scores (APRI and FIB4) in predicting the severity of liver disease in patients with hepatitis B. A retrospective analysis of 1434 patients with chronic HBV admitted between January 2020 and December 2024 was conducted at Sincan Tertiary Hospital. The positivity rates of the following antibodies were the focus of the study: anti-HDV, anti-HCV, and anti-HIV. In addition to these, the levels of HIV-RNA, HCV-RNA and HBV-DNA, as well as several biochemical markers (ALT, AST, INR, albumin, bilirubin and platelet count) were also evaluated. The APRI and FIB-4 scores were calculated. Of the 1434 patients, 49 (3.4%) tested positive for anti-HDV, 784 were screened for anti-HCV, and 749 were screened for anti-HIV. The positivity rates were 3.4% (27/784) and 3.4% (26/749), respectively. According to ROC analysis, the FIB-4 score had a statistically significant effect on predicting anti-HDV negativity (AUC = 0.59, p = 0.031). However, the APRI score was not a significant predictor for anti-HDV positivity (AUC = 0.53, p > 0.05). APRI and FIB-4 scores did not have a statistically significant discriminatory power in predicting anti-HCV and anti-HIV positivity (p > 0.05). The cut-off value for the FIB-4 score in predicting anti-HDV positivity was 1.72, with a sensitivity of 61.4% and a specificity of 42.9% (p = 0.031). Among the HCV/RNA-positive patients (n = 5), all were male, and two also had positive anti-HBe results with undetectable HBV/DNA levels. One HIV/RNA-positive patient, a foreign national, was confirmed to have HIV/HBV/HDV infection. All HBsAg-positive patients should undergo routine anti-HDV testing. Vaccination programmes are vital in preventing the spread of HDV. Dual screening strategies are essential for identifying infected individuals and developing prevention and treatment programmes. Anti-HDV positivity indicates advanced liver fibrosis, emphasising the importance of screening and monitoring. However, the limited accuracy of the APRI and FIB-4 scores for detecting coinfections highlights the need to integrate noninvasive methods with molecular diagnostics for precise management. Full article

People with HIV (PWH) receiving antiretroviral therapy (ART), despite a similar life expectancy, have a higher incidence of comorbidities than the general population. This study assessed the influence of proinflammatory biomarkers and clinical factors on mortality of PWH. We included PWH hospitalized from 2009 to 2014 who continued ART until 2023. The baseline lipid profile, CD4+ cell count, platelets, CRP, PCT, TNF-α, VCAM-1, and HCV and HBV coinfection were evaluated. Multivariable logistic regression was used to evaluate factors associated with mortality. Among 72 PWH, 19 were lost to a follow-up and 13 died before 2023. The mean follow-up was 12.07 years, while the mean time to death was 4.32 years. The main causes of death were cancer (n = 7) and drug-related death (n = 4). In the multivariate analysis, HCV coinfection, CRP ≥ 5 mg/L, PCT ≥ 0.05 ng/mL, and VCAM-1 ≥ 922 ng/mL were associated with higher odds of death. Although people who died had lower total cholesterol and triglyceride concentrations, these parameters were not associated with mortality. Determining HCV coinfections and CRP, PCT, and VCAM-1 levels may help identify PWH at increased risk of death for intensified monitoring. Care should also be taken of PWH with normal lipid parameters. Full article

Hepatitis B virus (HBV) infections remain a significant global health challenge, especially in low- and middle-income countries where access to healthcare services is often limited. This study aimed to assess the prevalence of hepatitis B virus (HBV), hepatitis delta virus (HDV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) co-infections in a cohort of 426,528 patients tested for HBsAg in Romania between 2018 and 2023. Of the 17,082 HBsAg-positive individuals (4.0% prevalence), the highest HBV positivity rates were observed in the 30–39 and over 60 age groups. Chronic HBV infection was identified in 13.2% of the cohort, with 3.6% testing positive for HBeAg, indicating active viral replication. Co-infection rates were 11.3% for HDV, 1.4% for HCV, and 0.45% for HIV. The incidence of HDV co-infection increased significantly from 2018 to 2023, particularly in older populations. HCV co-infection was more prevalent in individuals aged 50–59 and over 60, with a declining trend from 2020 onward. The study also revealed a weak correlation between liver enzyme levels (ALT and AST) and HBV viral load, suggesting that liver function tests may not fully reflect the severity of HBV infection. HIV co-infection was notably rare compared to other regions, likely due to regional healthcare interventions. The findings from our study highlight the need for targeted interventions, particularly for high-risk groups such as older adults and middle-aged individuals, to reduce the burden of chronic HBV and its complications. Full article

In 2020, the Eliminate Hepatitis C Initiative in the county of San Diego (COSD) was launched, a private–public joint endeavor between the COSD and the American Liver Foundation. We use epidemic modeling to assess whether the COSD is on track to reach its elimination targets (80% reduction in incidence, 65% reduction in hepatitis C virus (HCV)-related mortality by 2030 compared to 2015) and what intervention scale-up may be required. We adapted a previously developed dynamic, deterministic model of HCV transmission and disease progression among adults in the COSD, stratified by risk, age, gender, and human immunodeficiency virus (HIV) status. The model is calibrated to detailed historical epidemiological data on HCV burden, treatment, and mortality in the COSD. We project HCV infections and mortality under status quo HCV treatment (65%/year among people coinfected with HCV and HIV, 0–5%/year among others) and determine what treatment scale-up among those without HIV is required to achieve HCV elimination, with or without concomitant reductions in injection transmission risk from 2024 onward. We project an increase in new HCV infections in the COSD to 2213 [95% C.I.: 1069–3763] in 2030, a mean 91% relative increase between 2015 and 2030. HCV-related deaths are expected to decrease to 246 [95% C.I.: 180–295] in 2030, a mean relative decrease of 14% compared to 2015. The incidence elimination target could be achieved through increasing HCV treatment among those without HIV to a mean of 60%/year, similar to the level achieved among people coinfected with HCV and HIV. Combination interventions reduce the treatment needed; if injecting risk is reduced by 25%, then treating 48%/year could achieve elimination. The COSD is likely not on track to reach the incidence or mortality targets, but achieving the incidence target is possible if treatment rates overall are scaled-up to rates that have been achieved among people coinfected with HCV and HIV. Elimination is achievable but requires committed funding and expansion of comprehensive testing, linkage, and treatment programs alongside harm reduction initiatives. Full article

Direct-acting antivirals (DAA) are effective in patients with hepatitis C virus (HCV) infection, but there is little information about real-world effectiveness in people living with human immunodeficiency virus (PLH). The aim of this study was to determinate the effectiveness of DAA to achieve sustained virologic response at week 12 post-treatment (SVR12) in PLH with HCV coinfection and in people with HCV-monoinfection. We conducted a prospective cohort. The full analysis set (FAS) included all subjects enrolled in the study; the modified analysis set (MAS) excluded cases with missing data to evaluate SVR12. A total of 278 people were included, 130 (46.7%) with HCV/HIV-coinfection and 148 (53.2%) with HCV-monoinfection. In the HCV/HIV-coinfection group, 82 (63%) received GLE/PIB for 8 weeks, 45 (34.6%) received SOF/VEL for 12 weeks, and 3 (2.3%) were treated with SOF/VEL + RBV for 12 weeks. In the HCV-monoinfection group, 62 (41.8%) received GLE/PIB for 8 weeks, 28 (18.9%) received SOF/VEL for 12 weeks, and 58 (39.1%) participants were treated with SOF/VEL + RBV for 12 weeks. In the FAS analysis, SVR12 was 81.6% in the HCV/HIV-coinfection group and 86.4% in the HCV-monoinfection group (p = 0.128). In the MAS analysis, both groups achieved 100% of SVR12. In this cohort, the effectiveness of DAA to achieve SVR12 was similar between HCV/HIV-coinfection and HCV-monoinfection cases, regardless of advanced liver disease with no differences between treatment regimens. Full article

Background: Osteoporosis and vertebral fractures (VFs) are frequently observed in males living with HIV (MLWH). While bisphosphonates seem effective on bone mineral density (BMD) in MLWH, data on VFs are lacking. In this real-life longitudinal study performed on 118 MLWH (median age 53) who were followed-up for a median of 7 years, we aimed to evaluate the long-term efficacy of oral bisphosphonates on VFs in MLWH. Methods: The inclusion criteria were age >18, stable HIV infection, bisphosphonate-naïve, blood samples from the same laboratory, and three densitometries and morphometries performed with the same densitometer. Results: At baseline, VFs were detected in 29/118 patients (24.6%). Patients with VFs were older (p. 0.042), had longer HIV infection duration (p. 0.046) and antiretroviral exposure (p. 0.025), and demonstrated higher luteinizing hormone levels (LH, p. 0.044). Of the 29 patients with VFs at inclusion, 11 developed new VFs, of which 8 were under oral bisphosphonates (p. 0.018). Among the 89 without basal VFs, 11 developed VFs, of which 2 were under oral bisphosphonates. Patients with a worsened bone condition (regarding BMD and/or new VFs, n. 32) had more frequently high LH levels (>9.4 mIU/mL, p. 0.046) and higher HCV co-infection compared to patients with a stable bone condition (p. 0.045). It should be noted that 38.6% of patients discontinued oral bisphosphonates due to medical indication or personal choice, and 14.0% never started them. Conclusions: In conclusion, we found that oral bisphosphonates were not completely effective in preventing VFs, especially in patients with VFs at baseline; this is probably due to the multifactorial pathogenesis of fragility fractures in this population. A poor adherence to treatment and attention to gonadal function are also important issues in this population. Full article

Background/Objectives: The Elecsys^® HCV Duo immunoassay (Roche Diagnostics International Ltd., Rotkreuz, Switzerland) detects both antibodies to hepatitis C virus (anti-HCV) and HCV core antigen (HCV-Ag) and has shown excellent diagnostic performance in blood donor samples. We aim to validate its use for diagnosing chronic HCV infection and assessing sustained virological response (SVR) post-direct-acting antivirals (DAAs) in patients with or without HIV infection. Methods: Blood samples from 100 healthy controls, as well as 64 HCV mono-infection and 136 HCV-HIV coinfections, were collected before and 12–24 weeks after DAAs. The assay performance for determining active infection at baseline and SVR was compared with HCV RNA. Results: Overall, 156 (78.0%) of HCV-infected patients had HCV genotype 1, and the SVR rate was 96.5%. The sensitivity, specificity, and area under the ROC curve (AUROC) for HCV diagnosis at baseline were 99.50% (95% confidence interval [CI], 96.82–99.97%), 100% (95%CI, 95.39–100%), and 0.998 (95%CI, 0.992–1.003), respectively. The corresponding results for HCV-Ag in determining SVR were 57.14% (95%CI, 20.24–88.19%), 97.41% (95%CI, 93.73–99.04%), and 0.773 (95%CI, 0.543–1.003), respectively. The assay also exhibited comparable sensitivity and specificity between HCV mono- and coinfection. Conclusions: Our study showed that the Elecsys^® HCV Duo immunoassay effectively diagnosed HCV infection, regardless of HIV status, making it suitable for managing high-risk populations in resource-limited settings. Full article