{"title":"Beyond Transplantation: Cytomegalovirus Viremia as a Therapeutic Target in Non-Cytomegalovirus Syndromes.","authors":"Ghady Haidar","doi":"10.1093/infdis/jiaf648","DOIUrl":"https://doi.org/10.1093/infdis/jiaf648","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145971882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background & Aims Limited research exists on immune checkpoint inhibitors (ICIs)’ antiviral efficacy in HBV-related hepatocellular carcinoma (HCC). This study aimed to evaluate the impact of ICIs on multiple HBV markers and its correlation with HCC prognosis. Methods A retrospective cohort study was performed on 318 HBV-related HCC patients, including 268 who received ICIs (with/without targeted therapy; ICI group) and 50 who received targeted therapy alone (non-ICI group). Levels of quantitative HBsAg (qHBsAg), HBV DNA, HBV RNA and HBcrAg were monitored. Tumor response was evaluated using RECIST 1.1. Results Over a median 8.1-month follow-up, the ICI group showed a significantly greater decrease in all HBV markers. At week 96, the ICI group showed significantly higher cumulative incidences of HBsAg response (loss or ≥0.5 Log10 decline) (41.6% vs. 14.9%, p=0.006) and HBcrAg response (negativity or ≥1 Log10 decline) (46.3% vs. 18.1%, p=0.007) than non-ICI group, and a significantly faster achievement rate of HBV RNA response (negativity or ≥0.5 Log10 decline) (HR: 1.80, 95% CI: 1.08-2.99, p=0.021). Notably, the PD-1 inhibitors showed significantly better virological response efficacy than PD-L1 inhibitors (HR=2.04-5.43). The patients with lower levels of HBV markers at enrollment demonstrated significantly better overall survival (OS). Moreover, patients achieving virological response were associated with significantly better survival outcomes and tumor response, with HR ranging 1.64-8.06. Conclusions ICIs demonstrate dual therapeutic effects in HBV-related HCC, significantly reducing multiple HBV markers while concurrently enhancing prognosis in combination with antiviral therapy, emphasizing the importance of sustained virological suppression for optimal HCC outcomes.
{"title":"Immune checkpoint inhibitor-induced rapid decline in HBV markers improves the prognosis of HBV-related hepatocellular carcinoma patients","authors":"Yujie Ran, Minghui Zhu, Kunyuan Wang, Ying Xia, Yun Zhu, Mengya Zang, Shuai Kang, Qi Li, Xiaoyun Hu, Ying Wang, Fang Liu, Xiaowei Chen, Qian Zhao, Hongyan Liu, Dingli Liu, Huaiyu Chen, Jinzhang Chen, Yabing Guo, Rong Fan","doi":"10.1093/infdis/jiag036","DOIUrl":"https://doi.org/10.1093/infdis/jiag036","url":null,"abstract":"Background & Aims Limited research exists on immune checkpoint inhibitors (ICIs)’ antiviral efficacy in HBV-related hepatocellular carcinoma (HCC). This study aimed to evaluate the impact of ICIs on multiple HBV markers and its correlation with HCC prognosis. Methods A retrospective cohort study was performed on 318 HBV-related HCC patients, including 268 who received ICIs (with/without targeted therapy; ICI group) and 50 who received targeted therapy alone (non-ICI group). Levels of quantitative HBsAg (qHBsAg), HBV DNA, HBV RNA and HBcrAg were monitored. Tumor response was evaluated using RECIST 1.1. Results Over a median 8.1-month follow-up, the ICI group showed a significantly greater decrease in all HBV markers. At week 96, the ICI group showed significantly higher cumulative incidences of HBsAg response (loss or ≥0.5 Log10 decline) (41.6% vs. 14.9%, p=0.006) and HBcrAg response (negativity or ≥1 Log10 decline) (46.3% vs. 18.1%, p=0.007) than non-ICI group, and a significantly faster achievement rate of HBV RNA response (negativity or ≥0.5 Log10 decline) (HR: 1.80, 95% CI: 1.08-2.99, p=0.021). Notably, the PD-1 inhibitors showed significantly better virological response efficacy than PD-L1 inhibitors (HR=2.04-5.43). The patients with lower levels of HBV markers at enrollment demonstrated significantly better overall survival (OS). Moreover, patients achieving virological response were associated with significantly better survival outcomes and tumor response, with HR ranging 1.64-8.06. Conclusions ICIs demonstrate dual therapeutic effects in HBV-related HCC, significantly reducing multiple HBV markers while concurrently enhancing prognosis in combination with antiviral therapy, emphasizing the importance of sustained virological suppression for optimal HCC outcomes.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sumanth Cherukumilli,Adama M Keita,William Still,Kuangyi Charles Wei,Jane Juma,Hamidou Diallo,Allaye Traore,Oumar Coulibaly,Boubacar Togo,Mark A Holmes,Kate S Baker,J Kristie Johnson,Milagritos D Tapia,Samba O Sow,Karen L Kotloff
BACKGROUNDDespite data demonstrating the high prevalence of third-generation cephalosporin resistant gram-negative Enterobacterales (GNE) among children in sub-Saharan Africa, longitudinal descriptions of resistance among these pathogens from Francophone West Africa remain rare.METHODSWe conducted a retrospective analysis of pathogen-positive children 0-15 years old included in an invasive bacterial infection study at l'Hôpital Gabriel Touré (in Bamako, Mali) from 2005-2023. We aimed to describe changes in pathogen burden and non-Salmonella GNE resistance over time and compare in-hospital mortality between patients with and without non-Salmonella GNE pathogens. Isolates from 2021-2023 underwent whole genome sequencing to identify genes conferring antimicrobial resistance.RESULTSOf 3,803 pathogen-positive patients, 392 grew at least one non-Salmonella GNE pathogen. The proportion of pathogen-positive patients with non-Salmonella GNE increased (6% vs. 38%) from 2005-2023. Third-generation cephalosporin and multidrug resistance among non-Salmonella GNE increased from 30% and 55%, respectively, in 2005-2009, to 93% (both) by 2021-2023. Children 0-2 months old from outside Bamako and 3 months-15 years old from and from outside Bamako with non-Salmonella GNE had higher mortality odds (3.17, 95% CI 1.69-5.95; 2.13, 95% CI 1.44-3.14; and 2.25, 95% CI 1.38-3.66, respectively) than similar patients with other pathogens. Sequencing confirmed the presence of the emerging pathogen Pantoea dispersa and revealed genes conferring multidrug resistance.CONCLUSIONSData from this large pediatric referral center in Mali show a high and rising burden of multidrug-resistant gram-negative Enterobacterales. These patterns reflect concerns increasingly reported across sub-Saharan Africa, highlighting the urgency of strengthening antimicrobial access, diagnostics, and stewardship strategies in similar settings.
背景：尽管数据显示撒哈拉以南非洲儿童中第三代耐头孢菌素革兰氏阴性肠杆菌（GNE）的流行率很高，但西非法语区这些病原体的耐药性的纵向描述仍然很少。方法回顾性分析2005-2023年在l'Hôpital Gabriel tour（位于马里巴马科）进行的一项侵袭性细菌感染研究中0-15岁的病原体阳性儿童。我们的目的是描述病原体负担和非沙门氏菌GNE耐药性随时间的变化，并比较有和没有非沙门氏菌GNE病原体的患者的住院死亡率。对2021-2023株分离株进行全基因组测序，以确定赋予抗菌素耐药性的基因。结果3803例病原菌阳性患者中，392例至少有一种非沙门氏菌GNE病原菌。2005-2023年，非沙门氏菌GNE的病原体阳性患者比例增加（6%对38%）。第三代头孢菌素和非沙门氏菌GNE的多药耐药性分别从2005-2009年的30%和55%增加到2021-2023年的93%。巴马科城外0-2个月大的儿童和巴马科城外3 -15个月大的非沙门氏菌GNE患儿的死亡率高于其他病原体的类似患者（分别为3.17,95% CI 1.69-5.95; 2.13, 95% CI 1.44-3.14; 2.25, 95% CI 1.38-3.66）。测序证实了新出现的病原体泛菌的存在，并揭示了赋予多药耐药的基因。结论：来自马里这个大型儿科转诊中心的数据显示，多重耐药革兰氏阴性肠杆菌的负担很高，而且还在不断上升。这些模式反映了撒哈拉以南非洲各地越来越多报告的关切，突出了在类似环境中加强抗微生物药物获取、诊断和管理战略的紧迫性。
{"title":"Longitudinal Trends in Pediatric Non-Salmonella Gram-negative Enterobacterales Infections at a Tertiary Care Center in West Africa, 2005-2023.","authors":"Sumanth Cherukumilli,Adama M Keita,William Still,Kuangyi Charles Wei,Jane Juma,Hamidou Diallo,Allaye Traore,Oumar Coulibaly,Boubacar Togo,Mark A Holmes,Kate S Baker,J Kristie Johnson,Milagritos D Tapia,Samba O Sow,Karen L Kotloff","doi":"10.1093/infdis/jiag027","DOIUrl":"https://doi.org/10.1093/infdis/jiag027","url":null,"abstract":"BACKGROUNDDespite data demonstrating the high prevalence of third-generation cephalosporin resistant gram-negative Enterobacterales (GNE) among children in sub-Saharan Africa, longitudinal descriptions of resistance among these pathogens from Francophone West Africa remain rare.METHODSWe conducted a retrospective analysis of pathogen-positive children 0-15 years old included in an invasive bacterial infection study at l'Hôpital Gabriel Touré (in Bamako, Mali) from 2005-2023. We aimed to describe changes in pathogen burden and non-Salmonella GNE resistance over time and compare in-hospital mortality between patients with and without non-Salmonella GNE pathogens. Isolates from 2021-2023 underwent whole genome sequencing to identify genes conferring antimicrobial resistance.RESULTSOf 3,803 pathogen-positive patients, 392 grew at least one non-Salmonella GNE pathogen. The proportion of pathogen-positive patients with non-Salmonella GNE increased (6% vs. 38%) from 2005-2023. Third-generation cephalosporin and multidrug resistance among non-Salmonella GNE increased from 30% and 55%, respectively, in 2005-2009, to 93% (both) by 2021-2023. Children 0-2 months old from outside Bamako and 3 months-15 years old from and from outside Bamako with non-Salmonella GNE had higher mortality odds (3.17, 95% CI 1.69-5.95; 2.13, 95% CI 1.44-3.14; and 2.25, 95% CI 1.38-3.66, respectively) than similar patients with other pathogens. Sequencing confirmed the presence of the emerging pathogen Pantoea dispersa and revealed genes conferring multidrug resistance.CONCLUSIONSData from this large pediatric referral center in Mali show a high and rising burden of multidrug-resistant gram-negative Enterobacterales. These patterns reflect concerns increasingly reported across sub-Saharan Africa, highlighting the urgency of strengthening antimicrobial access, diagnostics, and stewardship strategies in similar settings.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Danuta M Skowronski, Charlene Ranadheera, Samantha E Kaweski, Suzana Sabaiduc, Lea Separovic, Gaby Makowski, Johnny Ung, Romina C Reyes, Bonnie Henry, Arianne Albert, Felicity Clemens, Darwyn Kobasa, Nathalie Bastien
Background Pre-existing immunity to emerging influenza viruses informs pandemic risk assessment. We compared cross-reactive neuraminidase (NA) antibody levels against avian influenza A(H5N1) by age and birth (imprinting) cohorts defined by periods of human influenza A subtype (H1N1, H2N2 or H3N2) circulation over the past century. Methods We used anonymized, residual sera collected from ten age groups spanning one to >80 years during an August 2024 cross-sectional serosurvey conducted in British Columbia, Canada. We assessed NA inhibition antibody titres by enzyme-linked lectin assay against clade 2.3.4.4b H5N1, and 2009 H1N1pdm09 and 1968 H3N2 pandemic strains Results Among 575 participants with median age 32 (IQR: 15-62) years, 404 (70%) had detectable anti-N1 titres >10 against H5N1, with 260 (45%), 182 (32%) and 98 (17%) having titres >40, >80 and >160, respectively. Anti-N1 titres against 2009 H1N1pdm09 and H5N1 were strongly correlated (r=0.86; 95%CI: 0.82-0.89), with both highest among young adults born 1997-2003 who were school-aged children during the 2009 H1N1 pandemic (427.9, 100.8), lowest among the youngest and least influenza-experienced pediatric cohorts born 2015-2023 (20.7, 6.8) and middle-aged adults born during the 1957-1967 H2N2 era (25.1, 10.7), thereafter increasing toward a similar secondary peak among the oldest cohorts born during the pre-1947 H1N1 era (387.3, 81.0). Conclusions A substantial proportion of the population has pre-existing anti-N1 against H5N1, with age-related variation reflecting H1N1 imprinting and exposure opportunities. Through heightened attack rates and shifts in immunological hierarchies, historic pandemics shape and expand the immune repertoire with implications for pre-immunity to emerging zoonotic threats.
{"title":"Cross-reactive H5N1 neuraminidase antibodies by age and influenza A imprinting cohorts of the past century: population-based serosurvey, British Columbia, Canada","authors":"Danuta M Skowronski, Charlene Ranadheera, Samantha E Kaweski, Suzana Sabaiduc, Lea Separovic, Gaby Makowski, Johnny Ung, Romina C Reyes, Bonnie Henry, Arianne Albert, Felicity Clemens, Darwyn Kobasa, Nathalie Bastien","doi":"10.1093/infdis/jiag030","DOIUrl":"https://doi.org/10.1093/infdis/jiag030","url":null,"abstract":"Background Pre-existing immunity to emerging influenza viruses informs pandemic risk assessment. We compared cross-reactive neuraminidase (NA) antibody levels against avian influenza A(H5N1) by age and birth (imprinting) cohorts defined by periods of human influenza A subtype (H1N1, H2N2 or H3N2) circulation over the past century. Methods We used anonymized, residual sera collected from ten age groups spanning one to >80 years during an August 2024 cross-sectional serosurvey conducted in British Columbia, Canada. We assessed NA inhibition antibody titres by enzyme-linked lectin assay against clade 2.3.4.4b H5N1, and 2009 H1N1pdm09 and 1968 H3N2 pandemic strains Results Among 575 participants with median age 32 (IQR: 15-62) years, 404 (70%) had detectable anti-N1 titres >10 against H5N1, with 260 (45%), 182 (32%) and 98 (17%) having titres >40, >80 and >160, respectively. Anti-N1 titres against 2009 H1N1pdm09 and H5N1 were strongly correlated (r=0.86; 95%CI: 0.82-0.89), with both highest among young adults born 1997-2003 who were school-aged children during the 2009 H1N1 pandemic (427.9, 100.8), lowest among the youngest and least influenza-experienced pediatric cohorts born 2015-2023 (20.7, 6.8) and middle-aged adults born during the 1957-1967 H2N2 era (25.1, 10.7), thereafter increasing toward a similar secondary peak among the oldest cohorts born during the pre-1947 H1N1 era (387.3, 81.0). Conclusions A substantial proportion of the population has pre-existing anti-N1 against H5N1, with age-related variation reflecting H1N1 imprinting and exposure opportunities. Through heightened attack rates and shifts in immunological hierarchies, historic pandemics shape and expand the immune repertoire with implications for pre-immunity to emerging zoonotic threats.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tanya E Libby, Angela Karani, Kirkby D Tickell, Donald Akech, Benson Singa, Doreen Rwigi, Kevin Kariuki, Nancy Onamu, Derrick Ounga, James A Berkley, Judd L Walson, J Anthony G Scott, Patricia B Pavlinac
Background Mass azithromycin distribution reduces child mortality in some settings, potentially through reductions in nasopharyngeal carriage of Streptococcus pneumoniae, but has been associated with increased antimicrobial resistance. Individual-level data are lacking on the impact of azithromycin on antimicrobial resistance over time. Methods We analyzed data from a double-blind, randomized placebo-controlled trial (ClinicalTrials.gov; NCT02414399) which followed 1,398 hospitalized Kenyan children to evaluate the impact of a 5-day course of oral azithromycin at discharge from hospital on pneumococcal carriage and the proportion of isolates (among a random sample) resistant to azithromycin. Randomization to azithromycin or placebo (1:1) was stratified by enrollment county (Kisii or Homa Bay). Using generalized estimating equations, we calculated prevalence ratios (PRs) and 95% confidence intervals for the intervention, adjusting for enrollment site. Results Overall, 1,253/1398 (89.6%) enrolled children received antibiotics during their hospitalization. Pneumococcal carriage at discharge was similar among children randomized to the azithromycin group (158/702 [22.5%]) compared to the placebo group (171/696 [24.6%]; p = 0.4) and did not differ at month 3 (65.6% vs 67.0%; PR:0.98[0.90, 1.06]) or month 6 (66.7% vs 66.5%; PR:1.00[0.92, 1.08]). At discharge, 15.7% of isolates were resistant to azithromycin and there was no difference between azithromycin-treated and placebo groups at month 3 (35/266 [13.2%] vs 32/256 [12.5%]; PR:1.06[0.86, 1.66]) or month 6 (41/245 [16.7%] vs 43/243 [17.6%]; PR:1.01[0.69,1.49]). Conclusions Azithromycin treatment did not effect pneumococcal carriage or antimicrobial resistance 3- or 6-months post-randomization. High inpatient antibiotic use in this recently discharged population may have reduced any further impact of azithromycin.
{"title":"The effect of a 5-day course of azithromycin on Streptococcus pneumoniae carriage and antimicrobial resistance among Kenyan children discharged from hospital","authors":"Tanya E Libby, Angela Karani, Kirkby D Tickell, Donald Akech, Benson Singa, Doreen Rwigi, Kevin Kariuki, Nancy Onamu, Derrick Ounga, James A Berkley, Judd L Walson, J Anthony G Scott, Patricia B Pavlinac","doi":"10.1093/infdis/jiag028","DOIUrl":"https://doi.org/10.1093/infdis/jiag028","url":null,"abstract":"Background Mass azithromycin distribution reduces child mortality in some settings, potentially through reductions in nasopharyngeal carriage of Streptococcus pneumoniae, but has been associated with increased antimicrobial resistance. Individual-level data are lacking on the impact of azithromycin on antimicrobial resistance over time. Methods We analyzed data from a double-blind, randomized placebo-controlled trial (ClinicalTrials.gov; NCT02414399) which followed 1,398 hospitalized Kenyan children to evaluate the impact of a 5-day course of oral azithromycin at discharge from hospital on pneumococcal carriage and the proportion of isolates (among a random sample) resistant to azithromycin. Randomization to azithromycin or placebo (1:1) was stratified by enrollment county (Kisii or Homa Bay). Using generalized estimating equations, we calculated prevalence ratios (PRs) and 95% confidence intervals for the intervention, adjusting for enrollment site. Results Overall, 1,253/1398 (89.6%) enrolled children received antibiotics during their hospitalization. Pneumococcal carriage at discharge was similar among children randomized to the azithromycin group (158/702 [22.5%]) compared to the placebo group (171/696 [24.6%]; p = 0.4) and did not differ at month 3 (65.6% vs 67.0%; PR:0.98[0.90, 1.06]) or month 6 (66.7% vs 66.5%; PR:1.00[0.92, 1.08]). At discharge, 15.7% of isolates were resistant to azithromycin and there was no difference between azithromycin-treated and placebo groups at month 3 (35/266 [13.2%] vs 32/256 [12.5%]; PR:1.06[0.86, 1.66]) or month 6 (41/245 [16.7%] vs 43/243 [17.6%]; PR:1.01[0.69,1.49]). Conclusions Azithromycin treatment did not effect pneumococcal carriage or antimicrobial resistance 3- or 6-months post-randomization. High inpatient antibiotic use in this recently discharged population may have reduced any further impact of azithromycin.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
James Kennedy, Sarah A Cooley, June Roman Fox, Kalen J Petersen, Elizabeth Westerhaus, Pat Reid, Linet Lopez, Beau M Ances
Background As persons with HIV (PWH) live longer, interactions between HIV, aging, and structural brain integrity become increasingly vital for understanding cognitive disorders. This study analyzed the effects of aging, HIV serostatus, and viral load on cognition and brain volumes in a large cohort of persons without HIV (PWoH), PWH with undetectable virus (PWHU) (≤50 copies/mL), and PWH with detectable virus (PHWD) (>50 copies/mL). Cross-sectional and longitudinal data were included. Methods Cognitive composites (NPZ4) and brain volumes were obtained from 259 PWoH, 264 PWHU and 84 PWHD with a total of 841 sessions. A series of generalized additive mixed models explored group differences in the relationship between age and cognition, age and regional brain volumes, and interactions between age and brain volumes on cognition. Results PWoH and PWHU exhibited similar change in cognitive performance with age, while PWHD exhibited a steeper decline compared to both. While both PWH groups had significantly smaller regional brain volumes compared to PWoH, the slopes of volume loss with age were similar across all groups except in the lentiform regions. Smaller brain volumes and increased age interacted for greater cognitive decline in PWHD. Conclusion PWH who achieve viral suppression do not exhibit accelerated decline in cognition or brain volumes compared to PWoH, while PWHD may be at an increased risk for accelerated cognitive decline. These findings highlight the clinical importance of managing viral load in aging PWH and suggest that once viral suppression is achieved, changes to brain integrity are not accelerated compared to PWoH.
{"title":"Longitudinal changes in cognition and brain imaging in persons with HIV","authors":"James Kennedy, Sarah A Cooley, June Roman Fox, Kalen J Petersen, Elizabeth Westerhaus, Pat Reid, Linet Lopez, Beau M Ances","doi":"10.1093/infdis/jiag029","DOIUrl":"https://doi.org/10.1093/infdis/jiag029","url":null,"abstract":"Background As persons with HIV (PWH) live longer, interactions between HIV, aging, and structural brain integrity become increasingly vital for understanding cognitive disorders. This study analyzed the effects of aging, HIV serostatus, and viral load on cognition and brain volumes in a large cohort of persons without HIV (PWoH), PWH with undetectable virus (PWHU) (≤50 copies/mL), and PWH with detectable virus (PHWD) (>50 copies/mL). Cross-sectional and longitudinal data were included. Methods Cognitive composites (NPZ4) and brain volumes were obtained from 259 PWoH, 264 PWHU and 84 PWHD with a total of 841 sessions. A series of generalized additive mixed models explored group differences in the relationship between age and cognition, age and regional brain volumes, and interactions between age and brain volumes on cognition. Results PWoH and PWHU exhibited similar change in cognitive performance with age, while PWHD exhibited a steeper decline compared to both. While both PWH groups had significantly smaller regional brain volumes compared to PWoH, the slopes of volume loss with age were similar across all groups except in the lentiform regions. Smaller brain volumes and increased age interacted for greater cognitive decline in PWHD. Conclusion PWH who achieve viral suppression do not exhibit accelerated decline in cognition or brain volumes compared to PWoH, while PWHD may be at an increased risk for accelerated cognitive decline. These findings highlight the clinical importance of managing viral load in aging PWH and suggest that once viral suppression is achieved, changes to brain integrity are not accelerated compared to PWoH.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tess E Peterson,Virginia S Hahn,Ruin Moaddel,Min Zhu,Jinshui Fan,Supriyo De,Sabina A Haberlen,Frank J Palella,Michael Plankey,Joel S Bader,Joao A C Lima,Robert E Gerszten,Jerome I Rotter,Gregory D Kirk,Damani A Piggott,Luigi Ferrucci,Joseph B Margolick,Todd T Brown,Wendy S Post,Katherine C Wu
BACKGROUNDPeople with HIV (PWH) are at higher risk of myocardial fibrosis and subsequent heart failure (HF) compared to people without HIV (PWOH). Mechanisms underlying this risk and its specificity to PWH are unclear.METHODSWe measured 2594 proteins in plasma obtained concurrently with cardiovascular magnetic resonance imaging among 342 PWH and PWOH. We estimated associations with HIV serostatus and myocardial fibrosis (elevated extracellular volume fraction, ECV ≥30% among women, ≥28% among men) using multivariable regression. Among an independent community-based cohort, we estimated associations between the identified signature and time to incident HF.RESULTSParticipants were age 55±6 years, 25% female, 61% PWH (88% on antiretroviral therapy, 74% undetectable HIV RNA), and 52% had elevated ECV. We identified 39 proteins and one cluster of 42 proteins that were higher among PWH vs. PWOH and positively associated with elevated ECV, independent of risk factors (FDR<0.05). Among an independent cohort of 3223 PWOH (age 68±9 years; 52% female; 118 incident HF cases over 9.8±1.4 years), we found this protein cluster and 34 of 39 individual proteins were associated with time to incident HF. This signature was statistically enriched for T cell activation, TNF signaling, ephrin signaling, and tissue maintenance and repair.CONCLUSIONWe identified an HIV-related proteomic signature associated with myocardial fibrosis regardless of HIV serostatus and that predicted incident HF among the general population. Our results identify several novel associations related to specific immune processes that may contribute to risk of myocardial fibrosis and subsequent HF among both PWH and PWOH.
{"title":"HIV-Associated Proteomic Signature of Myocardial Fibrosis and Incident Heart Failure.","authors":"Tess E Peterson,Virginia S Hahn,Ruin Moaddel,Min Zhu,Jinshui Fan,Supriyo De,Sabina A Haberlen,Frank J Palella,Michael Plankey,Joel S Bader,Joao A C Lima,Robert E Gerszten,Jerome I Rotter,Gregory D Kirk,Damani A Piggott,Luigi Ferrucci,Joseph B Margolick,Todd T Brown,Wendy S Post,Katherine C Wu","doi":"10.1093/infdis/jiag013","DOIUrl":"https://doi.org/10.1093/infdis/jiag013","url":null,"abstract":"BACKGROUNDPeople with HIV (PWH) are at higher risk of myocardial fibrosis and subsequent heart failure (HF) compared to people without HIV (PWOH). Mechanisms underlying this risk and its specificity to PWH are unclear.METHODSWe measured 2594 proteins in plasma obtained concurrently with cardiovascular magnetic resonance imaging among 342 PWH and PWOH. We estimated associations with HIV serostatus and myocardial fibrosis (elevated extracellular volume fraction, ECV ≥30% among women, ≥28% among men) using multivariable regression. Among an independent community-based cohort, we estimated associations between the identified signature and time to incident HF.RESULTSParticipants were age 55±6 years, 25% female, 61% PWH (88% on antiretroviral therapy, 74% undetectable HIV RNA), and 52% had elevated ECV. We identified 39 proteins and one cluster of 42 proteins that were higher among PWH vs. PWOH and positively associated with elevated ECV, independent of risk factors (FDR<0.05). Among an independent cohort of 3223 PWOH (age 68±9 years; 52% female; 118 incident HF cases over 9.8±1.4 years), we found this protein cluster and 34 of 39 individual proteins were associated with time to incident HF. This signature was statistically enriched for T cell activation, TNF signaling, ephrin signaling, and tissue maintenance and repair.CONCLUSIONWe identified an HIV-related proteomic signature associated with myocardial fibrosis regardless of HIV serostatus and that predicted incident HF among the general population. Our results identify several novel associations related to specific immune processes that may contribute to risk of myocardial fibrosis and subsequent HF among both PWH and PWOH.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Edward N Kankaka,Stephen Tomusange,Taddeo Kityamuweesi,Gabriel Quiros,Nicholas DiRico,Adam A Capoferri,Owen Baker,Erin E Brown,Jernelle Miller,Sharada Saraf,Charles Kirby,Briana Lynch,Jada Hackman,Craig Martens,Thomas C Quinn,Eileen P Scully,Amjad Khan,Art F Y Poon,Jessica L Prodger,Ronald M Galiwango,Steven J Reynolds,Andrew D Redd
BACKGROUNDAccurate estimation of HIV viremic time is valuable for understanding reservoir dynamics, and informing cure trials. Traditional approaches rely on serological assays or CD4 counts, which can lack quantitative precision. Sequence-based estimates using diversity in pre-treatment plasma RNA address this limitation, but are increasingly limited in the era of immediate ART initiation.METHODSWe developed Bayesian models to predict viremic time using sequence diversity from HIV reservoir sequences in two cohorts from Rakai, Uganda and Sweden. We computed six diversity metrics for gp41, RT, and matrix p17 regions. We fitted 36 Bayesian models per region using slope-fitting and weighting strategies, and evaluated them based on predictive accuracy and model diagnostics. The best-performing models were validated on participants with known diagnosis dates, but unknown seroconversion dates.RESULTSReservoir diversity increased with viremic time across all metrics. Models based on diversity from unique RT and gp41 sequences performed well, with improved predictions when combined, particularly using simple diversity metrics such as nucleotide diversity and mean TN93 distances. In validation, these models produced estimates and credible intervals that aligned with known HIV diagnosis dates; and inclusion of weights using log-transformed sequence counts increased the precision of prediction. Models using matrix p17, complex diversity metrics, or identical sequences showed weaker performance.CONCLUSIONSWe present a new Bayesian approach to estimate HIV viremic time from reservoir sequences with associated uncertainty estimates. Our prediction approach works across subtypes and chronic infection, uses simple diversity metrics, and may support research on HIV reservoir dynamics and cure.
{"title":"Estimating HIV-1 Viremic Time from Reservoir Sequence Diversity with Uncertainty Quantification.","authors":"Edward N Kankaka,Stephen Tomusange,Taddeo Kityamuweesi,Gabriel Quiros,Nicholas DiRico,Adam A Capoferri,Owen Baker,Erin E Brown,Jernelle Miller,Sharada Saraf,Charles Kirby,Briana Lynch,Jada Hackman,Craig Martens,Thomas C Quinn,Eileen P Scully,Amjad Khan,Art F Y Poon,Jessica L Prodger,Ronald M Galiwango,Steven J Reynolds,Andrew D Redd","doi":"10.1093/infdis/jiag020","DOIUrl":"https://doi.org/10.1093/infdis/jiag020","url":null,"abstract":"BACKGROUNDAccurate estimation of HIV viremic time is valuable for understanding reservoir dynamics, and informing cure trials. Traditional approaches rely on serological assays or CD4 counts, which can lack quantitative precision. Sequence-based estimates using diversity in pre-treatment plasma RNA address this limitation, but are increasingly limited in the era of immediate ART initiation.METHODSWe developed Bayesian models to predict viremic time using sequence diversity from HIV reservoir sequences in two cohorts from Rakai, Uganda and Sweden. We computed six diversity metrics for gp41, RT, and matrix p17 regions. We fitted 36 Bayesian models per region using slope-fitting and weighting strategies, and evaluated them based on predictive accuracy and model diagnostics. The best-performing models were validated on participants with known diagnosis dates, but unknown seroconversion dates.RESULTSReservoir diversity increased with viremic time across all metrics. Models based on diversity from unique RT and gp41 sequences performed well, with improved predictions when combined, particularly using simple diversity metrics such as nucleotide diversity and mean TN93 distances. In validation, these models produced estimates and credible intervals that aligned with known HIV diagnosis dates; and inclusion of weights using log-transformed sequence counts increased the precision of prediction. Models using matrix p17, complex diversity metrics, or identical sequences showed weaker performance.CONCLUSIONSWe present a new Bayesian approach to estimate HIV viremic time from reservoir sequences with associated uncertainty estimates. Our prediction approach works across subtypes and chronic infection, uses simple diversity metrics, and may support research on HIV reservoir dynamics and cure.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marc J T Blaauw,Adriana Navas,Victoria Rios Vásquez,Nadira Vadaq,Marvin A H Berrevoets,Twan Otten,Wilhelm A J W Vos,Louise E van Eekeren,Albert L Groenendijk,Gert Weijers,Esther Lutgens,Hans J P M Koenen,Marien I de Jonge,Mihai G Netea,Joost H W Rutten,Andre J A M van der Ven,Niels P Riksen
BACKGROUNDPeople living with HIV (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD), but the immunological mechanisms driving plaque formation remain unclear. This study investigated the association between peripheral immune cell subsets and carotid atherosclerotic plaques in PLHIV without prior clinical ASCVD.METHODSIn this multi-center cross-sectional study, virally suppressed PLHIV receiving antiretroviral therapy were enrolled from two Dutch cohorts: a discovery cohort (n= 994) and a validation cohort (n= 200). Between November 2019 and October 2021, participants underwent carotid ultrasound imaging to assess plaques using standardized criteria. Immune profiling was performed using high-dimensional flow cytometry of 355 immune cell populations. Associations with plaque were analyzed using linear regression adjusted for relevant confounders, and key findings were validated in the second cohort. Transcriptomic profiles of main cell populations were evaluated using deconvoluted bulk RNA sequencing to identify differential expression and pathway enrichment.RESULTSCarotid plaques were present in 584 participants (49%) - 502 of 994 (51%) in the discovery and 82 of 200 (41%) in the validation cohort. Plaques were associated with higher counts of several CD8+ T cell subsets, particularly PD-1-expressing cytotoxic T cells with an interferon secretion profile (CD8TC1PD1+). Transcriptomic analysis of CD8+ T cells revealed downregulated mitochondrial function and upregulated type 1 interferon and epidermal growth factor receptor (EGFR) signaling, indicating a senescent phenotype.CONCLUSIONSCD8+ T cell senescence may contribute to early atherosclerotic plaque formation in PLHIV. Targeting immune senescence could offer a novel strategy for cardiovascular risk reduction in this population.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT03994835.
{"title":"Functional and transcriptional senescence profiles of CD8+ T cells associate with the presence of carotid plaques in people living with HIV.","authors":"Marc J T Blaauw,Adriana Navas,Victoria Rios Vásquez,Nadira Vadaq,Marvin A H Berrevoets,Twan Otten,Wilhelm A J W Vos,Louise E van Eekeren,Albert L Groenendijk,Gert Weijers,Esther Lutgens,Hans J P M Koenen,Marien I de Jonge,Mihai G Netea,Joost H W Rutten,Andre J A M van der Ven,Niels P Riksen","doi":"10.1093/infdis/jiag018","DOIUrl":"https://doi.org/10.1093/infdis/jiag018","url":null,"abstract":"BACKGROUNDPeople living with HIV (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD), but the immunological mechanisms driving plaque formation remain unclear. This study investigated the association between peripheral immune cell subsets and carotid atherosclerotic plaques in PLHIV without prior clinical ASCVD.METHODSIn this multi-center cross-sectional study, virally suppressed PLHIV receiving antiretroviral therapy were enrolled from two Dutch cohorts: a discovery cohort (n= 994) and a validation cohort (n= 200). Between November 2019 and October 2021, participants underwent carotid ultrasound imaging to assess plaques using standardized criteria. Immune profiling was performed using high-dimensional flow cytometry of 355 immune cell populations. Associations with plaque were analyzed using linear regression adjusted for relevant confounders, and key findings were validated in the second cohort. Transcriptomic profiles of main cell populations were evaluated using deconvoluted bulk RNA sequencing to identify differential expression and pathway enrichment.RESULTSCarotid plaques were present in 584 participants (49%) - 502 of 994 (51%) in the discovery and 82 of 200 (41%) in the validation cohort. Plaques were associated with higher counts of several CD8+ T cell subsets, particularly PD-1-expressing cytotoxic T cells with an interferon secretion profile (CD8TC1PD1+). Transcriptomic analysis of CD8+ T cells revealed downregulated mitochondrial function and upregulated type 1 interferon and epidermal growth factor receptor (EGFR) signaling, indicating a senescent phenotype.CONCLUSIONSCD8+ T cell senescence may contribute to early atherosclerotic plaque formation in PLHIV. Targeting immune senescence could offer a novel strategy for cardiovascular risk reduction in this population.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT03994835.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"82 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dan-Yu Lin, Melissa A Mischell, Xinyu Zhang, Katie R Mollan, Ning Zhang, Dinelka Nanyakkara, Jessica R Keys, Becky Straub, David Wohl, William Fischer
In a prospective cohort study of 2,960 non-hospitalized adults with acute SARS-CoV-2 infection, older age, female sex, rural residence, high BMI, greater acute infection severity, chronic lung disease, and poorer general health at baseline were associated with higher risk and severity of postacute sequelae. Recent vaccination was associated with lower postacute sequelae risk and severity, while antiviral therapy was not.
{"title":"Incidence and Severity of Postacute Sequelae of SARS-CoV-2 Infection in the Omicron Era: A Prospective Cohort Study","authors":"Dan-Yu Lin, Melissa A Mischell, Xinyu Zhang, Katie R Mollan, Ning Zhang, Dinelka Nanyakkara, Jessica R Keys, Becky Straub, David Wohl, William Fischer","doi":"10.1093/infdis/jiag026","DOIUrl":"https://doi.org/10.1093/infdis/jiag026","url":null,"abstract":"In a prospective cohort study of 2,960 non-hospitalized adults with acute SARS-CoV-2 infection, older age, female sex, rural residence, high BMI, greater acute infection severity, chronic lung disease, and poorer general health at baseline were associated with higher risk and severity of postacute sequelae. Recent vaccination was associated with lower postacute sequelae risk and severity, while antiviral therapy was not.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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