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Virologic failure and emergent integrase strand transfer inhibitor drug resistance with long acting cabotegravir for HIV treatment: A meta-analysis
IF 11.8 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-26 DOI: 10.1093/cid/ciae631
Andrea Perez Navarro, Cameron T Nutt, Mark J Siedner, Suzanne M McCluskey, Andrew Hill
Background The long-acting injectable regimen of cabotegravir plus rilpivirine (CAB/RPV) emerged as an alternative to oral standard of care integrase strand transfer inhibitor (INSTI)-based regimens for individuals with adherence challenges or preference for reduced dosing schedules. Although oral INSTI regimens have a high barrier to emergent resistance, less is known about the potency and durability of CAB/RPV. Methods We reviewed clinical trial registries, PubMed, EMBASE, and conference abstract databases to identify published reports of CAB/RPV for HIV therapy. We abstracted data on virologic failure (VF) and treatment-emergent INSTI resistance at 48 weeks (range 24-52 weeks). We used single-proportion meta-analysis to summarize outcomes in three populations: 1) antiretroviral (ART)-naïve individuals initiating CAB/RPV following suppression on oral ART, 2) ART-experienced individuals switched to CAB/RPV with virologic suppression, and 3) ART-experienced individuals switched to CAB/RPV with detectable viremia. Cochrane’s RoB2.0 and ROBINS-1 tools assessed risk of bias. PROSPERO registration CRD42024543919. Results Thirty-three studies (N=9224) reported VF prevalence. Nineteen studies (N=5662) reported resistance data. VF prevalence was 1% (95% confidence intervals [CI] 1-3%) in induction-maintenance studies, 1% (CI 1-2%) in switch-suppressed studies, and 5% (CI 3-10%) in switch-viraemic studies. INSTI resistance prevalence among successfully genotyped participants at failure was 71% (CI 25-95%), 61% (CI 44-75%), and 41% (CI 20-65%) respectively. Dolutegravir cross-resistance was common (64% of those with emergent resistance). Discussion Although VF rates with CAB/RPV were low, INSTI resistance emerged in approximately 40-70% of individuals experiencing VF. These rates are significantly higher than those for oral INSTI-based regimens. Both individual-level and broader resistance surveillance may be warranted in individuals and populations with expanding CAB/RPV use.
{"title":"Virologic failure and emergent integrase strand transfer inhibitor drug resistance with long acting cabotegravir for HIV treatment: A meta-analysis","authors":"Andrea Perez Navarro, Cameron T Nutt, Mark J Siedner, Suzanne M McCluskey, Andrew Hill","doi":"10.1093/cid/ciae631","DOIUrl":"https://doi.org/10.1093/cid/ciae631","url":null,"abstract":"Background The long-acting injectable regimen of cabotegravir plus rilpivirine (CAB/RPV) emerged as an alternative to oral standard of care integrase strand transfer inhibitor (INSTI)-based regimens for individuals with adherence challenges or preference for reduced dosing schedules. Although oral INSTI regimens have a high barrier to emergent resistance, less is known about the potency and durability of CAB/RPV. Methods We reviewed clinical trial registries, PubMed, EMBASE, and conference abstract databases to identify published reports of CAB/RPV for HIV therapy. We abstracted data on virologic failure (VF) and treatment-emergent INSTI resistance at 48 weeks (range 24-52 weeks). We used single-proportion meta-analysis to summarize outcomes in three populations: 1) antiretroviral (ART)-naïve individuals initiating CAB/RPV following suppression on oral ART, 2) ART-experienced individuals switched to CAB/RPV with virologic suppression, and 3) ART-experienced individuals switched to CAB/RPV with detectable viremia. Cochrane’s RoB2.0 and ROBINS-1 tools assessed risk of bias. PROSPERO registration CRD42024543919. Results Thirty-three studies (N=9224) reported VF prevalence. Nineteen studies (N=5662) reported resistance data. VF prevalence was 1% (95% confidence intervals [CI] 1-3%) in induction-maintenance studies, 1% (CI 1-2%) in switch-suppressed studies, and 5% (CI 3-10%) in switch-viraemic studies. INSTI resistance prevalence among successfully genotyped participants at failure was 71% (CI 25-95%), 61% (CI 44-75%), and 41% (CI 20-65%) respectively. Dolutegravir cross-resistance was common (64% of those with emergent resistance). Discussion Although VF rates with CAB/RPV were low, INSTI resistance emerged in approximately 40-70% of individuals experiencing VF. These rates are significantly higher than those for oral INSTI-based regimens. Both individual-level and broader resistance surveillance may be warranted in individuals and populations with expanding CAB/RPV use.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"638 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunogenicity, Reactogenicity, and Safety of a Pentavalent Meningococcal ABCWY Vaccine in Adolescents and Young Adults who had Previously Received a Meningococcal ACWY Vaccine: Phase 3, Randomized, Controlled Clinical Study.
IF 11.8 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-26 DOI: 10.1093/cid/ciae622
Terry Nolan,Chiranjiwi Bhusal,Alejandro Hoberman,Conrado J Llapur,Olga Voloshyna,Ezekiel Fink,Angela Gentile,Garry Wallace,Peter C Richmond,Joseph B Domachowske,Thembile Mzolo,Maria Lattanzi,Daniela Toneatto,
BACKGROUNDA MenABCWY vaccine containing 4CMenB and MenACWY-CRM vaccine components has been developed to protect against the five meningococcal serogroups that cause most invasive disease cases.METHODSIn this phase 3 study (NCT04707391), healthy participants aged 15-25 years, who had received MenACWY vaccination ≥4 years previously, were randomized (1:1) to receive two MenABCWY doses six months apart or one MenACWY-CRM dose. Primary objectives were to demonstrate the non-inferiority of MenABCWY 1 month post-vaccination versus MenACWY-CRM, with a lower limit of 2-sided 95% confidence interval above -10% for group differences in 4-fold rise in human serum bactericidal antibody (hSBA) titers against serogroups ACWY, and to evaluate reactogenicity and safety. Secondary endpoints included percentages of participants with hSBA titers ≥lower limit of quantitation (LLOQ) against serogroups ACWY and vaccine antigen-specific serogroup B (MenB) indicator strains.RESULTSNon-inferiority of MenABCWY versus MenACWY-CRM was demonstrated following each MenABCWY dose. Percentages of participants with hSBA titers ≥LLOQ for serogroups ACWY were 97.9-98.9% and 99.5-100% following one and two MenABCWY doses, respectively, and 96.8-99.0% following one MenACWY-CRM dose. After two MenABCWY doses, 75.6-96.3% of participants had hSBA titers ≥LLOQ against MenB indicator strains. The MenABCWY vaccine was well tolerated in MenACWY-primed individuals with a favorable safety profile.CONCLUSIONSImmune responses against serogroups ACWY following one and two doses of investigational MenABCWY vaccine are non-inferior to those following MenACWY-CRM in MenACWY-primed adolescents and young adults. Robust immune responses were observed against MenB indicator strains after two MenABCWY doses administered 6 months apart.
{"title":"Immunogenicity, Reactogenicity, and Safety of a Pentavalent Meningococcal ABCWY Vaccine in Adolescents and Young Adults who had Previously Received a Meningococcal ACWY Vaccine: Phase 3, Randomized, Controlled Clinical Study.","authors":"Terry Nolan,Chiranjiwi Bhusal,Alejandro Hoberman,Conrado J Llapur,Olga Voloshyna,Ezekiel Fink,Angela Gentile,Garry Wallace,Peter C Richmond,Joseph B Domachowske,Thembile Mzolo,Maria Lattanzi,Daniela Toneatto,","doi":"10.1093/cid/ciae622","DOIUrl":"https://doi.org/10.1093/cid/ciae622","url":null,"abstract":"BACKGROUNDA MenABCWY vaccine containing 4CMenB and MenACWY-CRM vaccine components has been developed to protect against the five meningococcal serogroups that cause most invasive disease cases.METHODSIn this phase 3 study (NCT04707391), healthy participants aged 15-25 years, who had received MenACWY vaccination ≥4 years previously, were randomized (1:1) to receive two MenABCWY doses six months apart or one MenACWY-CRM dose. Primary objectives were to demonstrate the non-inferiority of MenABCWY 1 month post-vaccination versus MenACWY-CRM, with a lower limit of 2-sided 95% confidence interval above -10% for group differences in 4-fold rise in human serum bactericidal antibody (hSBA) titers against serogroups ACWY, and to evaluate reactogenicity and safety. Secondary endpoints included percentages of participants with hSBA titers ≥lower limit of quantitation (LLOQ) against serogroups ACWY and vaccine antigen-specific serogroup B (MenB) indicator strains.RESULTSNon-inferiority of MenABCWY versus MenACWY-CRM was demonstrated following each MenABCWY dose. Percentages of participants with hSBA titers ≥LLOQ for serogroups ACWY were 97.9-98.9% and 99.5-100% following one and two MenABCWY doses, respectively, and 96.8-99.0% following one MenACWY-CRM dose. After two MenABCWY doses, 75.6-96.3% of participants had hSBA titers ≥LLOQ against MenB indicator strains. The MenABCWY vaccine was well tolerated in MenACWY-primed individuals with a favorable safety profile.CONCLUSIONSImmune responses against serogroups ACWY following one and two doses of investigational MenABCWY vaccine are non-inferior to those following MenACWY-CRM in MenACWY-primed adolescents and young adults. Robust immune responses were observed against MenB indicator strains after two MenABCWY doses administered 6 months apart.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"154 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
LVAD versus CIED Infections: Distinct Entities, Distinct Suppression Strategies.
IF 8.2 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-24 DOI: 10.1093/cid/ciae647
Supavit Chesdachai, Larry M Baddour, Daniel C DeSimone

A distinction between infections of left ventricular assist devices (LVADs) and cardiac implantable electronic devices (CIEDs) is warranted as they differ markedly in incidence, microbiologic profiles, clinical presentations, and extraction feasibility. These differences necessitate tailored suppressive antibiotic therapy (SAT) strategies. This commentary highlights the need for device-specific SAT approaches.

{"title":"LVAD versus CIED Infections: Distinct Entities, Distinct Suppression Strategies.","authors":"Supavit Chesdachai, Larry M Baddour, Daniel C DeSimone","doi":"10.1093/cid/ciae647","DOIUrl":"https://doi.org/10.1093/cid/ciae647","url":null,"abstract":"<p><p>A distinction between infections of left ventricular assist devices (LVADs) and cardiac implantable electronic devices (CIEDs) is warranted as they differ markedly in incidence, microbiologic profiles, clinical presentations, and extraction feasibility. These differences necessitate tailored suppressive antibiotic therapy (SAT) strategies. This commentary highlights the need for device-specific SAT approaches.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Current and Future State of Vaccines for Lyme Disease
IF 11.8 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-23 DOI: 10.1093/cid/ciae639
Stanley A Plotkin, Eugene D Shapiro
Lyme disease is caused by Borrelia species that are transmitted by Ixodes ticks prevalent in parts of the United States and Europe. A Lyme vaccine containing the OspA antigens from the single Borrelia species most prevalent in the United States was marketed in the 1990s, but was withdrawn because of unproven concerns about safety, which led to insufficient sales. Since then, the incidence of Lyme disease has increased in the United States owing to the geographical spread of infected ticks. Lyme disease due to multiple different species of Borrelia also is widely prevalent in many European countries. New Lyme vaccines, using OspA antigens from multiple species of American and European Borrelia, are in advanced clinical development, and one such vaccine is in phase 3 trials. When licensed, new vaccines are likely to have an impact in preventing Lyme disease, although the need for periodic boosters remains to be defined.
{"title":"The Current and Future State of Vaccines for Lyme Disease","authors":"Stanley A Plotkin, Eugene D Shapiro","doi":"10.1093/cid/ciae639","DOIUrl":"https://doi.org/10.1093/cid/ciae639","url":null,"abstract":"Lyme disease is caused by Borrelia species that are transmitted by Ixodes ticks prevalent in parts of the United States and Europe. A Lyme vaccine containing the OspA antigens from the single Borrelia species most prevalent in the United States was marketed in the 1990s, but was withdrawn because of unproven concerns about safety, which led to insufficient sales. Since then, the incidence of Lyme disease has increased in the United States owing to the geographical spread of infected ticks. Lyme disease due to multiple different species of Borrelia also is widely prevalent in many European countries. New Lyme vaccines, using OspA antigens from multiple species of American and European Borrelia, are in advanced clinical development, and one such vaccine is in phase 3 trials. When licensed, new vaccines are likely to have an impact in preventing Lyme disease, although the need for periodic boosters remains to be defined.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"64 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Derivation and Validation of an Electronic Health Record Penicillin Allergy De-Labeling Prevalence Measure
IF 11.8 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-20 DOI: 10.1093/cid/ciae641
Kimberly G Blumenthal, Bohang Jiang, Andrew J King, Jushin T Mann, Yuqing Zhang, Alysse G Wurcel
With no standard method to capture penicillin allergy de-labeling prevalence across populations, we developed and validated a simple penicillin allergy de-labeling prevalence measure from electronic health records that achieved perfect sensitivity (100.0%), high specificity (99.4%), and strong agreement with a comprehensive algorithm that included free-text manual review (Kappa=0.997).
{"title":"Derivation and Validation of an Electronic Health Record Penicillin Allergy De-Labeling Prevalence Measure","authors":"Kimberly G Blumenthal, Bohang Jiang, Andrew J King, Jushin T Mann, Yuqing Zhang, Alysse G Wurcel","doi":"10.1093/cid/ciae641","DOIUrl":"https://doi.org/10.1093/cid/ciae641","url":null,"abstract":"With no standard method to capture penicillin allergy de-labeling prevalence across populations, we developed and validated a simple penicillin allergy de-labeling prevalence measure from electronic health records that achieved perfect sensitivity (100.0%), high specificity (99.4%), and strong agreement with a comprehensive algorithm that included free-text manual review (Kappa=0.997).","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"31 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Congenital toxoplasmosis: Fewer clinical signs at 3 years of age over the last 15 years but stable risk of materno-fetal transmission
IF 11.8 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-20 DOI: 10.1093/cid/ciae634
Martine Wallon, Elea Ksiazek, Antoine Journé, Damien Dupont, Jean Menotti, François Peyron, Christine Binquet
Risk and severity of congenital toxoplasmosis were estimated using data from 2,455 consecutive mother/child pairs. Clinical signs at 3 years were halved in the 177 children born since 2009 compared to 1996-2008 (OR=0.49; 95% Confidence interval 0.28-0.85). Maternofetal transmission rates remained stable from 1992 to 2021.
利用 2455 对连续母婴的数据估算了先天性弓形虫病的风险和严重程度。与1996-2008年相比,2009年以来出生的177名儿童3岁时的临床症状减少了一半(OR=0.49;95%置信区间为0.28-0.85)。从1992年到2021年,母婴传播率保持稳定。
{"title":"Congenital toxoplasmosis: Fewer clinical signs at 3 years of age over the last 15 years but stable risk of materno-fetal transmission","authors":"Martine Wallon, Elea Ksiazek, Antoine Journé, Damien Dupont, Jean Menotti, François Peyron, Christine Binquet","doi":"10.1093/cid/ciae634","DOIUrl":"https://doi.org/10.1093/cid/ciae634","url":null,"abstract":"Risk and severity of congenital toxoplasmosis were estimated using data from 2,455 consecutive mother/child pairs. Clinical signs at 3 years were halved in the 177 children born since 2009 compared to 1996-2008 (OR=0.49; 95% Confidence interval 0.28-0.85). Maternofetal transmission rates remained stable from 1992 to 2021.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"86 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Post-COVID Condition Risk Factors and Symptom Clusters and Associations with Return to Pre-COVID Health—Results from a 2021 Multi-State Survey
IF 11.8 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-20 DOI: 10.1093/cid/ciae632
Stacey L Konkle, Reed Magleby, Robert A Bonacci, Hannah E Segaloff, Lina V Dimitrov, Parag Mahale, Bozena Katic, Miriam Nji, Betsy Cadwell, Jean Y Ko, Dena Bushman, Julie Rushmore, Jennifer Cope, Sharon Saydah
Background Little is known about how symptoms or symptom clusters of Post-COVID Conditions (PCC) impact an individual’s return to pre-COVID health. Methods We used four state-level COVID-19 case reporting systems and patient-reported survey data to identify patients with PCC and associations with an individual’s return to pre-COVID health after laboratory-confirmed SARS-CoV-2 infection. Participants had a positive SARS-CoV-2 test between March–December 2020. Weighted regression models were used to 1) estimate prevalence of PCC; 2) identify risk factors associated with developing PCC; and 3) examine associations between PCC symptom clusters and return to pre-COVID health. Factor analysis was used to statistically identify post-COVID symptom clusters. Findings Prevalence of PCC in this population-based sample was 29·9% for persons with SARS-CoV-2 infection, during the pre-delta variant period (March–December 2020); 77·2% of persons experiencing PCC had not returned to pre-COVID health within 8–60 weeks after infection. Female sex, acute COVID-19 illness severity, and number of pre-existing comorbidities were significant risk factors associated with PCC. Myalgic encephalomyelitis/chronic fatigue syndrome-like symptoms, upper-respiratory symptoms, and gastrointestinal symptoms were significantly associated with not returning to pre-COVID health. Interpretation Understanding PCC symptom clustering may provide insight into pathophysiology, severity of PCC, and management for patients who have not returned to their usual state of health after SARS-CoV-2 infection. Tracking PCC can help measure the impact of COVID-19 vaccination and acute COVID-19-specific treatments on reducing PCC in the US.
{"title":"Post-COVID Condition Risk Factors and Symptom Clusters and Associations with Return to Pre-COVID Health—Results from a 2021 Multi-State Survey","authors":"Stacey L Konkle, Reed Magleby, Robert A Bonacci, Hannah E Segaloff, Lina V Dimitrov, Parag Mahale, Bozena Katic, Miriam Nji, Betsy Cadwell, Jean Y Ko, Dena Bushman, Julie Rushmore, Jennifer Cope, Sharon Saydah","doi":"10.1093/cid/ciae632","DOIUrl":"https://doi.org/10.1093/cid/ciae632","url":null,"abstract":"Background Little is known about how symptoms or symptom clusters of Post-COVID Conditions (PCC) impact an individual’s return to pre-COVID health. Methods We used four state-level COVID-19 case reporting systems and patient-reported survey data to identify patients with PCC and associations with an individual’s return to pre-COVID health after laboratory-confirmed SARS-CoV-2 infection. Participants had a positive SARS-CoV-2 test between March–December 2020. Weighted regression models were used to 1) estimate prevalence of PCC; 2) identify risk factors associated with developing PCC; and 3) examine associations between PCC symptom clusters and return to pre-COVID health. Factor analysis was used to statistically identify post-COVID symptom clusters. Findings Prevalence of PCC in this population-based sample was 29·9% for persons with SARS-CoV-2 infection, during the pre-delta variant period (March–December 2020); 77·2% of persons experiencing PCC had not returned to pre-COVID health within 8–60 weeks after infection. Female sex, acute COVID-19 illness severity, and number of pre-existing comorbidities were significant risk factors associated with PCC. Myalgic encephalomyelitis/chronic fatigue syndrome-like symptoms, upper-respiratory symptoms, and gastrointestinal symptoms were significantly associated with not returning to pre-COVID health. Interpretation Understanding PCC symptom clustering may provide insight into pathophysiology, severity of PCC, and management for patients who have not returned to their usual state of health after SARS-CoV-2 infection. Tracking PCC can help measure the impact of COVID-19 vaccination and acute COVID-19-specific treatments on reducing PCC in the US.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"31 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reinfection and resistance associated substitutions following a minimal monitoring approach for HCV treatment in MINMON trial.
IF 8.2 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-20 DOI: 10.1093/cid/ciae627
Win Min Han, Sunil Solomon, Laura Smeaton, Anchalee Avihingsanon, Sandra Wagner-Cardoso, Jiani Li, Aiyappa Parvangada, Mark Sulkowski, Susanna Naggie, Ross Martin, Hongmei Mo, Evguenia Maiorova, David Wyles

Background: Simplified approaches to HCV treatment delivery are needed to meet elimination goals. However, the impact of low-touch strategies on individuals at higher risk due to treatment failure or reinfection is unknown. We estimated HCV reinfection rates, and the impact of resistance associated substitutions (RASs) on response in the ACTG A5360 (MINMON) trial.

Methods: HCV RNA evaluations were scheduled at weeks 0, 24 (sustained viral response [SVR] visit), 48 and 72. Participants with post-entry HCV RNA ≥ lower limit of quantification (LLoQ) had deep sequencing of NS5A and NS5B genes performed. Phylogenetic analysis distinguished between reinfection and treatment failure. Reinfection rates per 100 person-years (PYS) were calculated with 95%CI constructed using Poisson distribution.

Results: Of 397 participants with post-entry HCV RNA, 29 had ≥LLoQ and available sequencing data. Of those 29, 5 participants initially designated as non-SVR, and 12 participants initially attaining SVR (evaluated at week-24) were determined to have reinfections (total 17 reinfections) (reinfection rate 3.9/100 PYS [95%CI 2.4-6.2]). All 17 participants with HCV reinfection were male (13 MSM and 15 with HIV). Of 29 had ≥LLoQ, 12 were identified as treatment failure. SVR (excluding reinfections) in presence and absence of baseline RAS was 93.5% (43/46) and 97% (337/346), respectively, with an overall SVR rate of 97.0% [95%CI 94.8-98.3] (385/397).

Conclusions: Accounting for reinfections, SVR in MINMON was 97.0% further supporting simplified HCV treatment. No significant difference in SVR was found by baseline velpatasvir RAS. The high reinfection rate, especially among MSM with HIV, underscores the need to scale-up evidence-based interventions to reduce reinfection.

{"title":"Reinfection and resistance associated substitutions following a minimal monitoring approach for HCV treatment in MINMON trial.","authors":"Win Min Han, Sunil Solomon, Laura Smeaton, Anchalee Avihingsanon, Sandra Wagner-Cardoso, Jiani Li, Aiyappa Parvangada, Mark Sulkowski, Susanna Naggie, Ross Martin, Hongmei Mo, Evguenia Maiorova, David Wyles","doi":"10.1093/cid/ciae627","DOIUrl":"https://doi.org/10.1093/cid/ciae627","url":null,"abstract":"<p><strong>Background: </strong>Simplified approaches to HCV treatment delivery are needed to meet elimination goals. However, the impact of low-touch strategies on individuals at higher risk due to treatment failure or reinfection is unknown. We estimated HCV reinfection rates, and the impact of resistance associated substitutions (RASs) on response in the ACTG A5360 (MINMON) trial.</p><p><strong>Methods: </strong>HCV RNA evaluations were scheduled at weeks 0, 24 (sustained viral response [SVR] visit), 48 and 72. Participants with post-entry HCV RNA ≥ lower limit of quantification (LLoQ) had deep sequencing of NS5A and NS5B genes performed. Phylogenetic analysis distinguished between reinfection and treatment failure. Reinfection rates per 100 person-years (PYS) were calculated with 95%CI constructed using Poisson distribution.</p><p><strong>Results: </strong>Of 397 participants with post-entry HCV RNA, 29 had ≥LLoQ and available sequencing data. Of those 29, 5 participants initially designated as non-SVR, and 12 participants initially attaining SVR (evaluated at week-24) were determined to have reinfections (total 17 reinfections) (reinfection rate 3.9/100 PYS [95%CI 2.4-6.2]). All 17 participants with HCV reinfection were male (13 MSM and 15 with HIV). Of 29 had ≥LLoQ, 12 were identified as treatment failure. SVR (excluding reinfections) in presence and absence of baseline RAS was 93.5% (43/46) and 97% (337/346), respectively, with an overall SVR rate of 97.0% [95%CI 94.8-98.3] (385/397).</p><p><strong>Conclusions: </strong>Accounting for reinfections, SVR in MINMON was 97.0% further supporting simplified HCV treatment. No significant difference in SVR was found by baseline velpatasvir RAS. The high reinfection rate, especially among MSM with HIV, underscores the need to scale-up evidence-based interventions to reduce reinfection.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Performance of diagnostic algorithms in patients with invasive pulmonary aspergillosis.
IF 8.2 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-20 DOI: 10.1093/cid/ciae633
Stefan Hatzl, Christina Geiger, Lisa Kriegl, Laura Scholz, Alexander C Reisinger, Philipp Kreuzer, Sonja Fruhwald, Albert Wölfler, Andreas Reinisch, Dirk von Lewinski, Gernot Schilcher, Martin Hoenigl, Philipp Eller, Robert Krause

Background: Invasive pulmonary aspergillosis (IPA), once limited to immunocompromised patients, is now a severe complication in critically ill ICU patients without classic risk factors. Due to the difficulty of obtaining histological evidence, its diagnosis relies on poorly tested algorithms in real-world settings.

Methods: We conducted a retrospective multicenter (n=9) cohort study including 202 patients with IPA. Patients were classified using a multistep process based on the European Organization for the Research and Treatment of Cancer/Mycosis Study Group (EORTC-MSG), Invasive-Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU), Aspergillus ICU (Asp-ICU), and Asp-ICU with biomarkers (Asp-ICU-BM) criteria. We then evaluated the predictive performance of these criteria against the clinical cohort and histologically proven cases.

Results: Among 202 patients, 78 had EORTC-MSG host factors and were classified accordingly, with the EORTC-MSG criteria achieving 100% agreement in identifying clinical and histologically proven cases. In 112 ICU patients without EORTC-MSG host factors, overall agreement was 53% for FUNDICU, 4% for Asp-ICU, and 26% for Asp-ICU-BM compared to the clinical cohort. Validation against histologically proven cases showed FUNDICU had 44% sensitivity and 75% specificity, Asp-ICU 6% sensitivity and 100% specificity, and Asp-ICU-BM 28% sensitivity and 63% specificity. Adding acute respiratory distress syndrome (ARDS) and post-cardiac surgery to the FUNDICU criteria improved sensitivity to 97% with a specificity of 63%. The remaining 12 patients lacked EORTC-MSG host factors and were not in the ICU, highlighting a novel classification system.

Conclusion: EORTC-MSG and FUNDICU IPA classification systems are useful for the assignment of most patients with IPA. Incorporating post-operative complications after cardiac surgery and ARDS enhanced the diagnostic accuracy of FUNDICU.

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引用次数: 0
Time to Staphylococcus aureus Blood Culture Positivity as a risk marker of Infective Endocarditis: A Retrospective Cohort Study 作为感染性心内膜炎风险标志的金黄色葡萄球菌血培养阳性时间:回顾性队列研究
IF 11.8 1区 医学 Q1 IMMUNOLOGY Pub Date : 2024-12-19 DOI: 10.1093/cid/ciae628
Martin Strömdahl, Karl Hagman, Karolina Hedman, Anna Westman, Magnus Hedenstierna, Johan Ursing
Background Endocarditis occurs in approximately 10-15% of patients with Staphylococcus aureus bacteremia. Short time to positivity (TTP) in blood culture flasks has been linked to endocarditis in smaller studies. This study evaluated the association between TTP and endocarditis in S. aureus bacteremia in a large cohort. Methods Adult patients with ≥1 S. aureus positive blood culture treated at a tertiary level, 500-bed hospital in Stockholm, Sweden between 2011-2021 were retrospectively identified. The primary outcome was the presence of infective endocarditis. Results A total of 1703 episodes of S. aureus bacteremia (23/1703 MRSA) in 1610 patients were included. Median age was 75 years (interquartile range [IQR] 63-84) and median Charlson comorbidity index was 2 (IQR 1-3). Echocardiography was performed in 1102/1703 (65%). Thirty-day mortality was 406/1703 (24%) and endocarditis was found in 154/1703 (9%). Median TTP was shorter in patients with endocarditis (9 [IQR 7-12] hours) compared to patients without endocarditis (13 [IQR 10-18] hours, p&lt;0.001). The risk of endocarditis decreased with 11% per hour (OR 0.89 [95% CI 0.54-0.92] p&lt;0.001) in a univariate analysis using TTP as a continuous variable. In multivariate analysis TTP&lt;13 hours (the median) was independently associated with endocarditis (OR 3.59, [95% CI 2.35-5.3] p&lt;0.001). The negative predictive value of TTP&gt;13 hours for endocarditis was 96% (95% CI 95-97). Conclusions Short TTP was associated with endocarditis. The negative predictive value of &gt;95% suggests that TTP&gt;13 hours can be used to risk stratify patients with S. aureus bacteremia.
{"title":"Time to Staphylococcus aureus Blood Culture Positivity as a risk marker of Infective Endocarditis: A Retrospective Cohort Study","authors":"Martin Strömdahl, Karl Hagman, Karolina Hedman, Anna Westman, Magnus Hedenstierna, Johan Ursing","doi":"10.1093/cid/ciae628","DOIUrl":"https://doi.org/10.1093/cid/ciae628","url":null,"abstract":"Background Endocarditis occurs in approximately 10-15% of patients with Staphylococcus aureus bacteremia. Short time to positivity (TTP) in blood culture flasks has been linked to endocarditis in smaller studies. This study evaluated the association between TTP and endocarditis in S. aureus bacteremia in a large cohort. Methods Adult patients with ≥1 S. aureus positive blood culture treated at a tertiary level, 500-bed hospital in Stockholm, Sweden between 2011-2021 were retrospectively identified. The primary outcome was the presence of infective endocarditis. Results A total of 1703 episodes of S. aureus bacteremia (23/1703 MRSA) in 1610 patients were included. Median age was 75 years (interquartile range [IQR] 63-84) and median Charlson comorbidity index was 2 (IQR 1-3). Echocardiography was performed in 1102/1703 (65%). Thirty-day mortality was 406/1703 (24%) and endocarditis was found in 154/1703 (9%). Median TTP was shorter in patients with endocarditis (9 [IQR 7-12] hours) compared to patients without endocarditis (13 [IQR 10-18] hours, p&amp;lt;0.001). The risk of endocarditis decreased with 11% per hour (OR 0.89 [95% CI 0.54-0.92] p&amp;lt;0.001) in a univariate analysis using TTP as a continuous variable. In multivariate analysis TTP&amp;lt;13 hours (the median) was independently associated with endocarditis (OR 3.59, [95% CI 2.35-5.3] p&amp;lt;0.001). The negative predictive value of TTP&amp;gt;13 hours for endocarditis was 96% (95% CI 95-97). Conclusions Short TTP was associated with endocarditis. The negative predictive value of &amp;gt;95% suggests that TTP&amp;gt;13 hours can be used to risk stratify patients with S. aureus bacteremia.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"14 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Clinical Infectious Diseases
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