Infectious Diseases and Therapy最新文献

Introduction: Although antiretroviral therapy (ART) has substantially improved treatment-related outcomes among people with HIV (PWH), individuals may still undergo ART regimen switches for clinical and non-clinical reasons. While prior studies have focused on virologic outcomes, contemporary data describing ART regimen switching in routine care in the US, especially among virologically suppressed PWH, are limited. In an evolving HIV treatment landscape, including expanding switch strategies, this study estimated the incidence of ART regimen switching among virologically suppressed PWH and characterized switch patterns.

Methods: This observational cohort study used prospectively collected, routine electronic health records data from the OPERA Cohort. Adult PWH who were active in care and on a complete ART regimen between July 1, 2024 and June 30, 2025 were eligible. An ART regimen switch was defined as any change in antiretroviral agent, excluding pharmacokinetic boosting agents. Incidence of ART regimen switching was assessed during this 1-year period, overall and among PWH who were virologically suppressed. PWH who underwent a switch were characterized. Pre- and post-suppressed switch regimens, as well as patterns of suppressed switching, were outlined.

Results: Among 73,078 PWH who were eligible, 8188 (11%) experienced ≥ 1 ART regimen switch during the 1-year study period. Of 68,147 individuals who were virologically suppressed to < 200 copies/ml during the study period, 6888 (10%) experienced ≥ 1 ART regimen switch while suppressed. The rate of suppressed switching was 14.5 per 100 person-years. Integrase inhibitors predominated both pre- and post-switch regimens. Overall, 51% of suppressed switches resulted in regimen simplification (lower pill count, fewer anchor agents, and/or transition to a complete long-acting injectable regimen).

Conclusions: In this large, contemporary US cohort, ART regimen switching was somewhat common and most frequently occurred among virologically suppressed PWH. These real-world findings on the incidence and patterns of virologically suppressed switches provide insight into new trends in treatment optimization and the need for new therapeutic options.

Introduction: Extensive real-world data in people with HIV (PWH) switching from non-nucleoside reverse transcriptase inhibitors (NNRTIs), in particular from rilpivirine (RPV)-based regimens to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), are lacking.

Methods: This is a single-center retrospective study. Inclusion criteria were PWH aged ≥ 18 years, virologically suppressed on NNRTI triple antiretroviral regimens. The primary endpoint was the proportion of PWH with HIV-RNA < 50 cp/mL at 12 months from time of switch to B/F/TAF.

Results: Overall, 214 PWH were included, of whom 105 (49.1%) were switching from RPV/FTC/TAF. After 12 months, the proportion of PWH with HIV-RNA < 50 copies/mL was 82.7% (95% confidence interval, CI, 77.1-87.2) at intention-to-treat (ITT) and 95.7% (95% CI 91.7-97.8) at missing=excluded (M=E) analysis. In the group switching from RPV/FTC/TAF, the proportion of PWH with HIV-RNA < 50 copies/mL at 12 months was 74.3% (95% CI 65.2-81.7) at ITT and 95.1% (95% CI 88.1-98.1) at M=E analysis. Two PWH (0.93%, 95% CI 0.26-3.34) experienced virological failure after switching to B/F/TAF, with no resistance mutations detected. Six treatment discontinuations were observed (2.8%, 95% CI 1.3-5.6). A decrease in low-density lipoprotein (LDL) cholesterol was documented when switching from RPV/FTC/TAF to B/F/TAF.

Conclusion: Switching to B/F/TAF from NNRTI-based regimens, particularly if RPV-based, showed high virological effectiveness and rare treatment discontinuations. No resistance mutations were detected at failure.

Introduction: Respiratory syncytial virus (RSV) is the leading cause of respiratory infections and hospitalization among infants and a major burden on pediatric emergency department (EDs). Nirsevimab has recently been introduced for universal use in all infants entering their first RSV season. However, real-world data on its public health impact are still limited, particularly regarding attendances at pediatric ED.

Methods: We conducted a retrospective, observational, pre-post intervention study at the Meyer Children's Hospital (Tuscany, Italy). The 2024-25 RSV season, when nirsevimab was firstly implemented, was compared with the three preceding seasons. ED attendances, hospitalization, and pediatric intensive care unit (PICU) admissions for lower respiratory tract infections (LRTIs) of any etiology were analyzed.

Results: During the 2024-25 season, overall ED attendances for LRTIs, regardless of etiology, decreased by 67.3%. Hospital admissions for LRTIs dropped by 64.7%, and PICU admissions by 86.2%. RSV-confirmed LRTIs declined by 96.5%.

Conclusions: Universal nirsevimab prophylaxis markedly reduced the burden of respiratory infections in eligible infants, leading to a significant reduction in the use of healthcare resources, including ED visits, hospitalization, and PICU admissions.

Introduction: Clinical evidence is needed for performance of novel coronavirus disease (COVID-19) molecular tests in asymptomatic populations to support regulatory decisions. To support claim expansion of a direct molecular test, clinical use and performance of the Cobas^® SARS-CoV-2 qualitative test for use on Cobas 5800/6800/8800 Systems ("candidate test") for detecting SARS-CoV-2 in individuals who are asymptomatic were investigated.

Methods: This study leveraged real-world data from the 2020 National Football League (NFL) COVID-19 Surveillance Program during August 1, 2020-January 3, 2021. NFL players and staff from 32 clubs had nasal samples prospectively collected on a near-daily basis. Samples underwent reverse transcription polymerase chain reaction (RT-PCR) testing by a single provider across five laboratories. The study population included individuals whose samples were tested on the candidate test. A comparator algorithm was constructed based on comparator test results and clinical adjudication within the NFL program. Results from the candidate test were compared against the comparator algorithm to calculate positive and negative percent agreements (PPA and NPA). Two-sided 95% confidence intervals (CIs) for PPA and NPA were determined (Wilson score method).

Results: A total of 1776 samples were included in the final analysis. All 11 samples with positive comparator status were positive on the candidate test (PPA 100% [95% CI 74.1, 100]). Of 1765 samples with negative comparator status, 1762 were negative on the candidate test (NPA 99.8% [95% CI 99.5, 99.9]). Results were consistent when stratified by age and sex.

Conclusions: Based on data collected during this occupational testing protocol, our study provides strong evidence supporting real-world performance of this test in an asymptomatic population. These findings, complemented by data from an existing clinical study, provided the totality-of-evidence that supported the US Food and Drug Administration clearance for the expanded claim of the candidate test for the qualitative detection of SARS-CoV-2 in the asymptomatic population.

Viral hepatitis remains a significant challenge for global public health and a leading cause of liver-related morbidity and mortality worldwide, with most cases caused by five hepatotropic viruses: hepatitis A, B, C, D, and E. The World Health Organization has established a goal to eliminate viral hepatitis as a public health threat by 2030. In recent years, advancements in our understanding of its pathogenesis have significantly propelled the development of antiviral drugs, particularly for hepatitis C, for which we now have highly effective therapies with cure rates exceeding 95%. However, achieving complete cures for hepatitis B and D continues to pose challenges, and effective treatments for hepatitis A and E are still lacking. A comprehensive understanding of the latest treatment advancements is crucial for guiding future drug development. This article reviews the most recent advancements in pharmacological interventions for viral hepatitis, summarizes current treatment methods, and provides an outlook on future research and therapeutic strategies, with the aim of improving patient outcomes and alleviating the global burden of liver diseases.

Multidrug-resistant (MDR) pathogens, exemplified by Klebsiella pneumoniae, pose a critical and escalating threat in low- and middle-income countries (LMICs), where limited diagnostic and therapeutic options exacerbate mortality. Bacteriophage (phage) therapy has re-emerged as a promising alternative, offering high specificity, biofilm disruption, and potential for low-cost production. However, a significant translational gap persists; while in vitro studies and results personalized phage therapy demonstrate efficacy, the pathway to clinical integration, especially in LMICs, remains obstructed by systemic barriers including the lack of local phage banks and undefined regulatory pathways. This review moves beyond a summary of biological promise to propose a novel, structured framework for implementation tailored to resource-limited health systems. We synthesize current evidence to introduce the 5-P roadmap, a cohesive strategy encompassing the establishment of integrated phage-host biobanks; development of context-appropriate preparations; rigorous preclinical validation emphasizing phage-antibiotic synergy; the parallel development of policy and regulatory pathways; and pilot clinical trials designed for subsequent health system integration. By addressing these interconnected pillars simultaneously, this framework provides an actionable blueprint to advance phage therapy from a laboratory concept to a scalable, equitable, and sustainable adjunct within national antimicrobial resistance strategies in LMICs.

Introduction: The hospitalization burden of human metapneumovirus (HMPV) in Spain was estimated assessing disease manifestations and risk factors to guide future vaccine strategies.

Methods: This study was a retrospective analysis of Spain's National Hospital Data System (CMBD) from 2016-2023, performed using ICD-10-CM diagnosis codes, with age-stratified analyses for children under 6 years and adults over 60 years, assessing comorbidities and associated mortality risks.

Results: A total of 4824 hospitalizations were identified; 75% in children, 16% in older adults. Bronchiolitis dominated in children while pneumonia was most common in older adults. Overall annual hospitalization rate was 18.70 hospitalizations per 100,000 in children up to 5 years old, and the annual hospitalization rate was 0.79 hospitalizations per 100,000 in adults over 60 years, Hospital costs totaled over €22 million, and, beyond this overall burden, expenditures showed a significant year-on-year increasing trend. There were 2 deaths among children < 6 years, 18 in individuals between 16 and 59 years and 74 in adults over 60 years old, reaching a case fatality rate of 9.65% in adults, with higher risk associated with kidney failure, liver disease, and cancer.

Conclusions: HMPV poses a significant burden on vulnerable groups in Spain. Despite underdiagnosis, rising cases post-COVID highlight the need for targeted prevention. These findings offer a foundation for public health planning and vaccine prioritization.

Introduction: The incidence of herpes zoster (HZ) is increasing globally. Despite the availability of a highly effective recombinant zoster vaccine (RZV), vaccination rates are still low in the United States, especially among racially and ethnically minoritized (REM) and socially vulnerable groups. There is an urgent need to identify obstacles to vaccination in these communities and develop effective strategies to increase confidence in the RZV.

Methods: From August 2024 to December 2024, we conducted a community-based educational intervention in San Bernardino County, California, partnering with five churches in neighborhoods with high Centers for Disease Control and Prevention (CDC) Social Vulnerability Index scores. The intervention included a 45-min presentation on HZ, its complications, and RZV recommendations. Participants aged 18 + completed pre- and post-surveys to assess attitudes, knowledge, and behaviors. Descriptive statistics summarized outcomes, while a two-proportion Z-test and Fisher's exact test evaluated changes in vaccine literacy.

Results: A total of 156 individuals completed the pre-intervention survey, and 134 completed the post-intervention survey. All identified as REM, with 99% in vulnerable neighborhoods. Sixty-three percent had at least one co-morbid illness, and 46% had received info about HZ or RZV before the session. At baseline, 57% believed they were at risk of HZ, but 75% found the education session "extremely effective" in reassessing their risk. Significant improvements in vaccine literacy, especially regarding disease and age-based recommendations, were observed, with correct responses increasing post-intervention (p < 0.05). Following the intervention, 82% reported a high likelihood of receiving RZV, and 90% a high likelihood of recommending it.

Conclusions: This study demonstrates the feasibility and acceptability of a faith-based, community-led educational intervention to address barriers to RZV uptake among vulnerable REM populations. Using trusted community infrastructure can support equitable expansion of adult immunization programs to reduce preventable HZ disparities.