Journal of Infectious Diseases最新文献

{"title":"Imipenem Pharmacokinetics/Pharmacodynamics in Preclinical Hollow Fiber Model, Dose Finding in Virtual Patients, and Clinical Evidence of Efficacy for Mycobacterium abscessus Lung Disease.","authors":"Sanjay Singh, Tawanda Gumbo, Jann-Yuan Wang, Gunavanthi D Boorgula, Andrew Burke, Hung-Ling Huang, Pamela J McShane, Rodolfo Amaro-Galvez, Jane E Gross, Santosh Aryal, Scott K Heysell, Shashikant Srivastava","doi":"10.1093/infdis/jiae601","DOIUrl":"10.1093/infdis/jiae601","url":null,"abstract":"<p><strong>Background: </strong>Guideline-based therapy (GBT) for Mycobacterium abscessus (Mab) lung disease achieves sputum culture conversion (SCC) rates of 35%. This poor GBT efficacy is mirrored in the hollow fiber system model of Mab (HFS-Mab). While imipenem is part of GBT, its biologic effect, with or without β-lactamase inhibitors, is unproven.</p><p><strong>Methods: </strong>We performed imipenem-relebactam minimum inhibitory concentration (MIC) in 122 Mab isolates, and an exposure-response study in the HFS-Mab using human intrapulmonary pharmacokinetics. The percentage of time that concentration persisted above the MIC (TMIC), mediating maximal effect in the HFS-Mab, was used as the exposure target for dose finding in a Monte Carlo experiment including 10 000 virtual patients. For real-world evidence, we performed a patient, intervention (imipenem), comparison (no β-lactam), and outcome (SCC) (PICO) analysis.</p><p><strong>Results: </strong>Imipenem killed 1.32 log10 colony-forming units/mL below the day 0 level in HFS-Mab. The average target exposure for imipenem was a TMIC of 47.9% (SD, 9.77%). Infusion of 1 g every 6 hours achieved the target in >90% of virtual patients in Monte Carlo experiments. The pharmacokinetic-pharmacodynamic MIC break point was 1 mg/L. In PICO analyses, the median time to SCC was 470 days in comparators, 311 days for imipenem added on to a failing regimen, and 37 days in newly treated patients (P = .049). The odds ratio for SCC when imipenem was part of the initial regimen, versus comparators, was 12.5 (95% confidence interval, 1.47--84.55). No patients receiving imipenem experienced treatment-limiting adverse events, compared with 2 of 7 comparators (P = .046). Middlebrook 7H9 broth MIC distribution, read at 24 hours, was better correlated with patient responses than cation-adjusted Mueller-Hinton broth.</p><p><strong>Conclusions: </strong>Imipenem demonstrated biologic effect in the HFS-Mab and in patients. Imipenem-relebactam doses of 1 g every 6 hours are recommended.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1521-1531"},"PeriodicalIF":4.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12475910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenacapavir Plus 2 Broadly Neutralizing Antibodies, Teropavimab and Zinlirvimab, for People With HIV-1 Highly Susceptible to Either Teropavimab or Zinlirvimab.","authors":"Joseph J Eron, Paul P Cook, Megha L Mehrotra, Hailin Huang, Marina Caskey, Gordon E Crofoot, Linda Gorgos, Laurie A VanderVeen, Yanan Zheng, Sean E Collins, Olayemi O Osiyemi, Cynthia Brinson, Edwin DeJesus","doi":"10.1093/infdis/jiaf159","DOIUrl":"10.1093/infdis/jiaf159","url":null,"abstract":"<p><strong>Background: </strong>The combination of 2 broadly neutralizing antibodies (bNAbs), teropavimab and zinlirvimab, plus the capsid inhibitor lenacapavir, is a potential twice-yearly regimen for HIV-1 treatment. The level of bNAb susceptibility to maintain virologic suppression is unknown; therefore, we evaluated this combination in participants meeting stringent viral sensitivity criteria to only 1 of the 2 bNAbs.</p><p><strong>Methods: </strong>This was a pilot study within a proof-of-concept phase 1b study.</p><p><strong>Results: </strong>No serious treatment-emergent adverse events occurred and 8 of 10 participants remained virologically suppressed at week 26.</p><p><strong>Conclusions: </strong>More inclusive bNAb susceptibility criteria may be appropriate for future studies of this combination treatment. Clinical Trials Registration. NCT04811040.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"1440-1444"},"PeriodicalIF":5.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial and Viral Coinfections in Adult Patients Hospitalized With COVID-19 Throughout the Pandemic: A Multinational Cohort Study in the EuCARE Project.","authors":"Pontus Hedberg, Karol Serwin, Maria Francesca Greco, Joana P V Pereira, Dovile Juozapaite, Sara De Benedittis, Francesca Bai, Nadine Lübke, Tobias Wienemann, Iuri Fanti, Florian König, Nico Pfeifer, Rolf Kaiser, Maurizio Zazzi, Alessandro Cozzi-Lepri, Daniel Naumovas, Giulia Marchetti, Milosz Parczewski, Björn-Erik Ole Jensen, Francesca Incardona, Anders Sönnerborg, Pontus Nauclér","doi":"10.1093/infdis/jiaf167","DOIUrl":"10.1093/infdis/jiaf167","url":null,"abstract":"<p><strong>Background: </strong>Limited evidence exists on how bacterial and viral coinfections have developed since the SARS-CoV-2 Omicron variant emerged. We investigated whether community-onset coinfections in adult patients hospitalized with COVID-19 differed during the wild type, Alpha, Delta, and Omicron periods and whether such coinfections were associated with an increased risk of mortality.</p><p><strong>Methods: </strong>We conducted a multinational cohort study including COVID-19 hospitalizations until 30 April 2023 in 5 European countries. The outcome was bacterial and viral coinfections based on 5 test modalities. Variant periods were compared with regard to occurrences of coinfections and risk ratios for coinfections (Omicron vs pre-Omicron), as well as association with in-hospital mortality (Omicron vs pre-Omicron).</p><p><strong>Results: </strong>A total of 29 564 cases were included: 12 601 wild type, 5256 Alpha, 2433 Delta, and 9274 Omicron. The coinfection rate was 2.6% (327/12 601) for wild type, 2.0% (105/5256) for Alpha, 3.2% (77/2433) for Delta, and 7.9% (737/9274) for Omicron. Omicron had a significantly increased risk ratio of coinfection when compared with preceding variants (1.88 [95% CI, 1.53-2.32], P < .001). These results were consistent across several subgroup analyses. An increased occurrence (19% [232/1246] vs 11% [3042/28 318]) and adjusted risk (1.69 [95% CI, 1.49-1.91], P < .001) of in-hospital mortality were observed in patients with a verified coinfection as compared with patients without a coinfection.</p><p><strong>Conclusions: </strong>Bacterial and viral coinfections were more prevalent during the Omicron period as compared with preceding variants. Such coinfections were associated with an increased risk of in-hospital mortality, calling for sustained monitoring and clinical vigilance.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e1091-e1101"},"PeriodicalIF":5.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12247819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and Genomic Characterization of Recalcitrant Enterococcal Bacteremia: A Multicenter Prospective Cohort Study (VENOUS).","authors":"Shelby R Simar, Truc T Tran, Kirsten B Rydell, Rachel L Atterstrom, Pranoti V Sahasrabhojane, An Q Dinh, Marissa G Schettino, Haley S Slanis, Alex E Deyanov, Andie M DeTranaltes, Dierdre B Axell-House, William R Miller, Jose M Munita, David Tobys, Harald Seifert, Lena M Biehl, Marcus Zervos, Geehan Suleyman, Jagjeet Kaur, Victoria Warzocha, Rossana Rosa, Renzo O Cifuentes, Lilian M Abbo, Luis Shimose, Catherine Liu, Katherine Nguyen, Ashleigh Miller, Samuel A Shelburne, Blake M Hanson, Cesar A Arias","doi":"10.1093/infdis/jiaf358","DOIUrl":"10.1093/infdis/jiaf358","url":null,"abstract":"<p><strong>Background: </strong>Patients with recalcitrant enterococcal bloodstream infections are at greater risk of adverse outcomes. We identified patients in the 2016-2022 Vancomycin-Resistant Enterococcal Bacteremia Outcomes Study (VENOUS) cohort experiencing recalcitrant bloodstream infections for further clinical and genomic characterization.</p><p><strong>Methods: </strong>Bacteremia episodes were considered \"persistent\" if there was a lack of clearance on day four while receiving ≥ 48 hours of active therapy and recurrent if there was clearance during hospitalization with a subsequent positive culture (collectively, \"recalcitrant\" bacteremia). A matched comparison group of non-recalcitrant bacteremia patients was chosen in a 2:1 control:case ratio. Isolates were subjected to short- and long-read whole-genome sequencing. Hybrid assemblies were created using a custom pipeline.</p><p><strong>Findings: </strong>A total of 46 recalcitrant infections from 41 patients were identified. Patients with persistent bacteremia were more often admitted to the ICU upon admission relative to controls. E. faecalis strains causing persistent infections had a significantly higher proportion of genes associated with carbohydrate utilization relative to controls. Representation of functional groups associated with mutated genes was disparate between E. faecium and E. faecalis index and persistent isolates, suggesting species-specific adaptation.</p><p><strong>Discussion: </strong>Enterococcal isolates causing recalcitrant bacteremia were genomically diverse, indicating that strain-specific signatures are not drivers of persistence. However, comparisons of index vs. persistent isolates revealed that E. faecium may be genetically pre-adapted to cause persistent infection, and site-specific structural variation during infection suggests the role of differential gene expression in adaptation and persistence. This data lays groundwork for future studies to define signatures of enterococcal adaptation during bacteremia.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hygromycin A treatment of Borrelia burgdorferi-infected Peromyscus leucopus suggests potential as a reservoir-targeted antibiotic.","authors":"Stephanie S You, Muskan Shrestha, Jeffrey S Bourgeois, Luke H Clendenen, Nadja Leimer, Kim Lewis, Sam R Telford, Linden T Hu","doi":"10.1093/infdis/jiaf363","DOIUrl":"https://doi.org/10.1093/infdis/jiaf363","url":null,"abstract":"<p><p>Lyme disease spirochetes are maintained in natural reservoirs before spilling over into human populations. Targeting these reservoirs with vaccinations or antibiotics could impact the B. burgdorferi enzootic cycle and reduce the risk of human Lyme disease. In this work we report that the narrow spectrum antibiotic hygromycin A is sufficient to disrupt B. burgdorferi transmission from the main eastern U.S. reservoir, Peromyscus leucopus, to ticks. Additionally, hygromycin A-containing baits can clear B. burgdorferi from P. leucopus. These studies lay the foundation for the use of hygromycin A as a reservoir-targeted antibiotic to eradicate B. burgdorferi in the wild.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secreted chorismate mutase: A novel prognostic factor in Mycobacterium intracellulare pulmonary disease.","authors":"Juye Bae, Ju-Young Lee, Hyejun Seo, Jake Whang, Joong-Yub Kim, Jae-Joon Yim, Bum-Joon Kim, Nakwon Kwak","doi":"10.1093/infdis/jiaf360","DOIUrl":"https://doi.org/10.1093/infdis/jiaf360","url":null,"abstract":"<p><strong>Objectives: </strong>Secreted chorismate mutase (S-CM) is known to act as a virulence factor in mycobacterial infections by inhibiting macrophage apoptosis. This study aims to investigate genetic variations in S-CM among Mycobacterium intracellulare strains and evaluate their influence on the clinical progression of M. intracellulare-pulmonary disease (PD).</p><p><strong>Methods: </strong>Patients diagnosed with M. intracellulare-PD who received treatment between January 1, 2020, and December 31, 2023, at Seoul National University Hospital were included. Clinical isolates collected at treatment initiation were assessed for subspecies classification and S-CM genetic variations. Treatment outcomes were analyzed based on subspecies and S-CM mutation status. J774A.1 murine macrophages were infected with type strains (ATCC13950T) carrying S-CM expression plasmids and clinical isolates. Macrophage apoptosis and bacterial colony-forming units (CFUs) were quantified.</p><p><strong>Results: </strong>Among the 118 isolates, 57 were identified as M. intracellulare subspecies intracellulare (Typical M. intracellulare, TMI), 53 as M. paraintracellulare, and eight as other subspecies. A C276A mutation causing S-CM truncation was detected in 24 isolates (20.3%), all belonging to TMI. TMI strains with S-CM truncation demonstrated a higher rate of culture conversion than those with intact S-CM (adjusted hazard ratio: 2.17, 95% confidence interval: 1.08-4.34, P = 0.029). In murine macrophages, TMI strains with truncated S-CM induced higher levels of apoptosis and lower CFUs, whereas expressing intact S-CM in a type strain with naturally truncated S-CM reduced apoptosis and increased bacterial burden.</p><p><strong>Conclusions: </strong>S-CM truncation in M. intracellulare enhances macrophage apoptosis, yielding reduced bacterial burden, decreased pathogenicity, and improved treatment responses.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated suPAR levels, organ dysfunction and death in children hospitalized with malaria: considerations for use as a risk stratification tool.","authors":"Charles Ssuuna, Hridesh Mishra, Michael T Hawkes, Veselina Stefanova, Aleksandra Leligdowicz, Michael Lintner-Rivera, Anthony Batte, Kathleen Zhong, Sophie Namasopo, Robert O Opoka, Kevin C Kain, Andrea L Conroy","doi":"10.1093/infdis/jiaf327","DOIUrl":"https://doi.org/10.1093/infdis/jiaf327","url":null,"abstract":"<p><p>Soluble urokinase-type plasminogen activator receptor (suPAR) is an emerging critical illness biomarker. Circulating suPAR levels are elevated in severe malaria and are associated with mortality. The present study evaluated clinical predictors of elevated plasma suPAR (≥15ng/mL). Elevated suPAR occurred in 22.1% of 1226 Ugandan children with severe malaria, and was independently associated with severe acute kidney injury, hyperlactatemia, and coma as well as biomarkers of immune and endothelial activation. An optimized clinical decision algorithm that prioritizes suPAR testing for children with clinical danger signs, including coma and kidney injury could improve the identification of children at highest risk of mortality.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One Hundred Days, Incalculable Losses.","authors":"Emily J Erbelding","doi":"10.1093/infdis/jiaf317","DOIUrl":"https://doi.org/10.1093/infdis/jiaf317","url":null,"abstract":"","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytolethal Distending Toxin-increased DNA damage and ploidy involve the YAP/TAZ-TEAD signaling pathway.","authors":"Ruxue Jia, Lamia Azzi-Martin, Mariana Saraiva, Elodie Sifré, Pierre Dubus, Christine Varon, Armelle Ménard","doi":"10.1093/infdis/jiaf312","DOIUrl":"https://doi.org/10.1093/infdis/jiaf312","url":null,"abstract":"<p><strong>Background: </strong>Bacterial genotoxins, CDT and colibactin, cause severe DNA damage in host cells and impair the DNA-damage response, leading to genomic instability. Some phenotypes induced by these genotoxins (actin cytoskeleton remodeling, stress fibers accumulation, disturbance of focal adhesion, cell-cell junctions' disassembly, increased ploidy and genome instability, endoreplication) are known to involve the Hippo signaling pathway, suggesting a link between some effects induced by these toxins and Hippo pathway.</p><p><strong>Methods: </strong>We investigated the Hippo signaling pathway in normal and cancer-derived epithelial intestinal and hepatic cell lines following intoxication with CDT/CdtB and colibactin.</p><p><strong>Results: </strong>We have shown that active CdtB subunit of CDT modulates the expression of transcripts and proteins of the Hippo downstream central transcriptional coactivators YAP/TAZ. CdtB exposure drove increased TEAD-mediated transcription confirmed by the upregulation of direct TEAD target genes. Inhibition of the YAP/TAZ binding to TEADs (verteporfin and K-975) dampened the effects of CdtB, particularly DNA damage and repair, and increased ploidy. These findings suggest that YAP/TAZ-TEAD signaling is involved in increased ploidy in cells surviving the DNA damage induced by CDT/CdtB. In addition, exposure to colibactin, a genotoxic metabolite produced by Escherichia coli, induced similar effects.</p><p><strong>Conclusions: </strong>Overall, these data show that infection with genotoxin-producing bacteria involves the YAP/TAZ-TEAD signaling pathway to control ploidy following DNA damage in epithelial cells.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial DNA Haplogroups, Biomarkers of Inflammation and Immune Activation, and Risk of Diabetes in Veterans with and without HIV.","authors":"Aiwei Yan, Suman Kundu, David C Samuels, Samuel Bailin, Ke Xu, Kaku So-Armah, Adeel A Butt, Mariana Gerschenson, Matthew Bidwell Goetz, Margaret Doyle, Russell Tracy, Vincent C Marconi, Amy Justice, Matthew Freiberg, John R Koethe, Todd Hulgan","doi":"10.1093/infdis/jiaf304","DOIUrl":"https://doi.org/10.1093/infdis/jiaf304","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (DM) is common among people with HIV (PWH). We previously reported that DM risk was greater in women of African ancestry with HIV who had mitochondrial DNA (mtDNA) haplogroup L3. We examined haplogroup associations with DM and selected soluble and cellular immune biomarkers among PWH and those without HIV in the Veterans Aging Cohort Study (VACS) Biomarker Cohort.</p><p><strong>Methods: </strong>VACS participants had mtDNA haplogroups determined from genome-wide genotyping and adjudicated DM outcomes. Serum IL-6, D-dimer, and soluble CD14 were quantified, and cellular phenotyping performed by flow cytometry, on blood collected 2005-2007. Analyses included logistic and Cox regression of prevalent and incident DM, stratified by self-reported ancestry and HIV status, and adjusted for selected covariates.</p><p><strong>Results: </strong>mtDNA haplogroups, soluble and/or cellular biomarkers, and DM outcomes were available for 2019 participants (65% with HIV; 68% non-Hispanic Black; 95% male). Among 781 Black PWH, mtDNA haplogroup L3 (40%) was associated with incident DM (HR 1.56; 95% CI 1.01-2.40) adjusting for covariates including senescent (CD28-negative) CD4+ T-cells, which were lower in Black PWH having haplogroup L3 vs. other African haplogroups (p=0.05). No other haplogroups were associated with DM. There were no significant associations observed in Veterans without HIV, although the effect size was similar.</p><p><strong>Conclusion: </strong>mtDNA haplogroup L3 was associated with incident DM in predominantly male non-Hispanic Black PWH, replicating an association reported previously. This haplogroup was associated with fewer senescent CD4+ T-cells, but the association with DM was independent of T-cell phenotype.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}