Antibiotic prophylaxis for spontaneous bacterial peritonitis (SBPPr) in patients with cirrhosis has been considered standard of care since the 1990s and is currently recommended by several major gastroenterological societies. However, the evidence supporting this practice is weak and there is no clear mortality benefit. The unintended consequences of this strategy are not insignificant, both at the patient and population level. Recent evidence suggests that SBPPr may even cause harm. Since the widespread implementation of SBPPr three decades ago, our overall approach to antibiotic use has shifted. We now recognize the growing threat of antimicrobial resistance (AMR), the potential harms of antibiotics, and the vital role of antimicrobial stewardship. In light recent developments and evidence, there is an urgent need for infectious disease, antimicrobial stewardship, and hepatology leaders to collaborate to develop an updated and cohesive approach to SBPPr.
{"title":"Rethinking Antibiotic Prophylaxis for Spontaneous Bacterial Peritonitis in Patients with Cirrhosis: First, Do No Harm.","authors":"J Daniel Markley, Jasmohan S Bajaj","doi":"10.1093/cid/ciaf047","DOIUrl":"https://doi.org/10.1093/cid/ciaf047","url":null,"abstract":"<p><p>Antibiotic prophylaxis for spontaneous bacterial peritonitis (SBPPr) in patients with cirrhosis has been considered standard of care since the 1990s and is currently recommended by several major gastroenterological societies. However, the evidence supporting this practice is weak and there is no clear mortality benefit. The unintended consequences of this strategy are not insignificant, both at the patient and population level. Recent evidence suggests that SBPPr may even cause harm. Since the widespread implementation of SBPPr three decades ago, our overall approach to antibiotic use has shifted. We now recognize the growing threat of antimicrobial resistance (AMR), the potential harms of antibiotics, and the vital role of antimicrobial stewardship. In light recent developments and evidence, there is an urgent need for infectious disease, antimicrobial stewardship, and hepatology leaders to collaborate to develop an updated and cohesive approach to SBPPr.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078787","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}
Ethan A Smith, Ginny M Javier, Ashrit Multani, Omer Eugene Beaird, Pryce Gaynor, Lauren Yanagimoto-Ogawa, Joanna Schaenman, Paul Allyn, George Alfarhat, Tara Vijayan, Alyssa Ziman, Omai Garner
Given declining COVID convalescent plasma (CCP) collection and increasing scarcity, we compared anti-SARS-CoV-2 IgG antibody titers between CCP, intravenous immunoglobulin (IVIG) and fresh frozen plasma (FFP). Herein, we report comparative anti-SARS-CoV-2 IgG antibody titers between five lots of each blood product, using the DiaSorin Liaison® SARS-CoV-2 TrimericS IgG assay.
{"title":"Anti-SARS-CoV-2 IgG Antibody Titers in Cotemporary lots of Intravenous Immune Globulin and Fresh Frozen Plasma Compared to COVID Convalescent Plasma.","authors":"Ethan A Smith, Ginny M Javier, Ashrit Multani, Omer Eugene Beaird, Pryce Gaynor, Lauren Yanagimoto-Ogawa, Joanna Schaenman, Paul Allyn, George Alfarhat, Tara Vijayan, Alyssa Ziman, Omai Garner","doi":"10.1093/cid/ciaf045","DOIUrl":"https://doi.org/10.1093/cid/ciaf045","url":null,"abstract":"<p><p>Given declining COVID convalescent plasma (CCP) collection and increasing scarcity, we compared anti-SARS-CoV-2 IgG antibody titers between CCP, intravenous immunoglobulin (IVIG) and fresh frozen plasma (FFP). Herein, we report comparative anti-SARS-CoV-2 IgG antibody titers between five lots of each blood product, using the DiaSorin Liaison® SARS-CoV-2 TrimericS IgG assay.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078782","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}
Heli Harvala, Katy Davison, Mhairi Webster, Claire Reynolds, Graham P Taylor
Background HTLV is associated with adult T-cell leukaemia/lymphoma and myelopathy. Here we present virological and epidemiological data on HTLV screening of blood donations in England between 2002 and 2021, implemented to prevent its transmission via blood transfusion. Methods Data on HTLV testing of blood donations was reviewed; it was initially conducted in pools (2002-2012) and subsequently using individual samples (all donors, 2013-2016; first-time donors and non-leucodepleted component donors, 2017-2021). Data included annual number of donations screened, initial and repeat reactives as well as confirmed positives. Further information, such as likely source of infection, was obtained for HTLV-positives. Results Over the 20-year study period, a total of 30,679,741 blood donations were screened for HTLV in England. Under pooled screening strategy, the annual rate of repeat reactive donations remained <5:100,000. However, this rate increased to 51:100,000 with individual screening and further to 123:100,000 with selective screening. A total of 5032 samples were repeat reactive, of which 278 were confirmed HTLV-positives. Although the specificity under each scenario exceeded 99.9%, the rate of repeat reactives was around 50-fold higher in individual compared to pooled screening. Most HTLV infected were UK-born, most likely acquired their infection unknowingly through breast feeding or heterosexual intercourse with an individual associated with an HTLV-endemic country. Conclusions These data highlight that pooled testing can be advantageous in low-prevalence settings due to its high specificity and reduced non-specific reactivity. Whether pooling is an applicable strategy to tackle the burden of HTLV infection in resource poor, HTLV-endemic countries requires further investigations.
{"title":"HTLV screening of blood donations in England between 2002 and 2021 – Comparison of screening strategies","authors":"Heli Harvala, Katy Davison, Mhairi Webster, Claire Reynolds, Graham P Taylor","doi":"10.1093/cid/ciaf053","DOIUrl":"https://doi.org/10.1093/cid/ciaf053","url":null,"abstract":"Background HTLV is associated with adult T-cell leukaemia/lymphoma and myelopathy. Here we present virological and epidemiological data on HTLV screening of blood donations in England between 2002 and 2021, implemented to prevent its transmission via blood transfusion. Methods Data on HTLV testing of blood donations was reviewed; it was initially conducted in pools (2002-2012) and subsequently using individual samples (all donors, 2013-2016; first-time donors and non-leucodepleted component donors, 2017-2021). Data included annual number of donations screened, initial and repeat reactives as well as confirmed positives. Further information, such as likely source of infection, was obtained for HTLV-positives. Results Over the 20-year study period, a total of 30,679,741 blood donations were screened for HTLV in England. Under pooled screening strategy, the annual rate of repeat reactive donations remained &lt;5:100,000. However, this rate increased to 51:100,000 with individual screening and further to 123:100,000 with selective screening. A total of 5032 samples were repeat reactive, of which 278 were confirmed HTLV-positives. Although the specificity under each scenario exceeded 99.9%, the rate of repeat reactives was around 50-fold higher in individual compared to pooled screening. Most HTLV infected were UK-born, most likely acquired their infection unknowingly through breast feeding or heterosexual intercourse with an individual associated with an HTLV-endemic country. Conclusions These data highlight that pooled testing can be advantageous in low-prevalence settings due to its high specificity and reduced non-specific reactivity. Whether pooling is an applicable strategy to tackle the burden of HTLV infection in resource poor, HTLV-endemic countries requires further investigations.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"24 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077491","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}
Clinical science in the field of infectious diseases moved at a rapid pace in 2024. Among the highlights were multiple trials of new antibiotics and new approaches to prevent infections. Concerning trends, with outbreaks of dengue, measles, mpox, and highly pathogenic avian influenza A in 2024, demonstrate the importance of infectious diseases and the continued need for further advances through clinical science. This review highlights some of the most important trials and clinical trends in infectious diseases over the past year.
{"title":"What’s Hot This Year in ID Clinical Science","authors":"Jeffrey A Freiberg, Patty W Wright","doi":"10.1093/cid/ciaf037","DOIUrl":"https://doi.org/10.1093/cid/ciaf037","url":null,"abstract":"Clinical science in the field of infectious diseases moved at a rapid pace in 2024. Among the highlights were multiple trials of new antibiotics and new approaches to prevent infections. Concerning trends, with outbreaks of dengue, measles, mpox, and highly pathogenic avian influenza A in 2024, demonstrate the importance of infectious diseases and the continued need for further advances through clinical science. This review highlights some of the most important trials and clinical trends in infectious diseases over the past year.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"57 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072491","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}
Troy Grennan,Saira Mohammed,Joshua Edward,Tessa Tattersall,Amit K Gupta,Joyce Seto,Michelle Dennehy,Marc G Romney,Wendy Zhang,Jenny Li,Jason Trigg,Viviane D Lima,Stephen Juwono,Jason Wong,Guijun Zhang,Julio S G Montaner,Mark W Hull
BACKGROUNDMen who have sex with men (MSM) and transgender women experience high sexually transmitted infection (STI) rates. This study evaluated the feasibility of doxycycline pre-exposure prophylaxis (doxyPrEP) for STI prevention in these key populations.METHODSSexually-active MSM and transgender women without HIV with prior syphilis were recruited. Participants initiated HIV PrEP with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) daily for 48 weeks, and were randomized 1:1 to daily doxyPrEP for 48 weeks (immediate arm), or doxyPrEP initiated at 24 weeks (deferred arm). Primary outcomes included adherence, measured using questionnaires, along with tolerability; STI incidence (chlamydia, gonorrhea, syphilis) was a secondary outcome. Nasal carriage of S. aureus was assessed serially for doxycycline resistance.RESULTSFifty-two participants were enrolled into the immediate (n=26) and deferred (n=26) arms. At 48 weeks, self-reported adherence (≥95%) was 75.0% vs. 66.7% (p=0.538) for TDF/FTC, and 70.8% vs. 61.9% (p=0.526) for doxycycline in the immediate vs. deferred arms, respectively. No doxyPrEP-related serious adverse events occurred. Incidence of any STI at 24 weeks was reduced in the immediate vs. deferred arms, and over 48 weeks, being on doxycycline (vs. being off; i.e. first 24 weeks of deferred arm) was associated with STI reduction (adjusted odds ratio [aOR] 0.36; 95 % confidence interval [CI] 0.15-0.89). Emergent doxycycline-resistant S. aureus was identified in six individuals, with five in the immediate arm (p=0.077).CONCLUSIONSDual HIV/doxyPrEP is feasible and associated with a significant reduction in incident STI. Further evaluation of dosing strategies, efficacy and impact on antimicrobial resistance is warranted.
{"title":"A pilot, randomized controlled trial of Dual Daily HIV and sexually transmitted infection pre-exposure prophylaxis using tenofovir disoproxil fumarate/emtricitabine and doxycycline in gay, bisexual and other men who have sex with men and transgender women: The DuDHS Study.","authors":"Troy Grennan,Saira Mohammed,Joshua Edward,Tessa Tattersall,Amit K Gupta,Joyce Seto,Michelle Dennehy,Marc G Romney,Wendy Zhang,Jenny Li,Jason Trigg,Viviane D Lima,Stephen Juwono,Jason Wong,Guijun Zhang,Julio S G Montaner,Mark W Hull","doi":"10.1093/cid/ciaf043","DOIUrl":"https://doi.org/10.1093/cid/ciaf043","url":null,"abstract":"BACKGROUNDMen who have sex with men (MSM) and transgender women experience high sexually transmitted infection (STI) rates. This study evaluated the feasibility of doxycycline pre-exposure prophylaxis (doxyPrEP) for STI prevention in these key populations.METHODSSexually-active MSM and transgender women without HIV with prior syphilis were recruited. Participants initiated HIV PrEP with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) daily for 48 weeks, and were randomized 1:1 to daily doxyPrEP for 48 weeks (immediate arm), or doxyPrEP initiated at 24 weeks (deferred arm). Primary outcomes included adherence, measured using questionnaires, along with tolerability; STI incidence (chlamydia, gonorrhea, syphilis) was a secondary outcome. Nasal carriage of S. aureus was assessed serially for doxycycline resistance.RESULTSFifty-two participants were enrolled into the immediate (n=26) and deferred (n=26) arms. At 48 weeks, self-reported adherence (≥95%) was 75.0% vs. 66.7% (p=0.538) for TDF/FTC, and 70.8% vs. 61.9% (p=0.526) for doxycycline in the immediate vs. deferred arms, respectively. No doxyPrEP-related serious adverse events occurred. Incidence of any STI at 24 weeks was reduced in the immediate vs. deferred arms, and over 48 weeks, being on doxycycline (vs. being off; i.e. first 24 weeks of deferred arm) was associated with STI reduction (adjusted odds ratio [aOR] 0.36; 95 % confidence interval [CI] 0.15-0.89). Emergent doxycycline-resistant S. aureus was identified in six individuals, with five in the immediate arm (p=0.077).CONCLUSIONSDual HIV/doxyPrEP is feasible and associated with a significant reduction in incident STI. Further evaluation of dosing strategies, efficacy and impact on antimicrobial resistance is warranted.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"36 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062082","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}
Peyman Banooni, Bernard Gonik, Cristina Epalza, Osvaldo Reyes, Shabir A Madhi, Grace Devota Gomez-Go, Khalequ Zaman, Conrado Juan Llapur, Eduardo López-Medina, Thorsten Stanley, Anu Kantele, Li-Min Huang, Marisa Márcia Mussi-Pinhata, Jonas Dewulf, Joanne M Langley, Claudia Seidl, Martin Ota, Martha Kirabo, Bruno Anspach, Ilse Dieussaert, Ouzama Henry, Joon Hyung Kim, Marta Picciolato
Background: In this phase 3 trial of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine (RSVPreF3-Mat), a higher rate of preterm birth was observed in the vaccine (6.8%) versus the placebo group (4.9%). Trial enrollment and vaccination were stopped. Results of investigations into this safety signal were reported previously. Here, we describe end-of-trial efficacy, immunogenicity, and safety results.
Methods: Women 18-49 years old were randomized 2:1 to receive one dose of RSVPreF3-Mat (n=3557) or placebo (n=1771) at 240/7-340/7 weeks' gestation. Primary outcomes were any and severe medically assessed RSV-associated lower respiratory tract disease (MA-RSV-LRTD) in infants until 6 months post-birth and safety until 12 months post-birth. Other efficacy outcomes were evaluated, along with immunogenicity (until 6 months post-partum/birth) and safety in mothers and infants.
Results: Efficacy in infants until 6 months post-birth was 65.5% (95% credible interval: 37.5-82.0) against any MA-RSV-LRTD, 69.0% (33.0-87.6) against severe MA-RSV-LRTD, and 50.1% (-3.6-75.8) against RSV hospitalization; it waned over time thereafter. Efficacy against MA-RSV-LRTD was 47.8% (-25.8-77.3) in low- and middle-income and 75.9% (46.1-91.5) in high-income countries. RSVPreF3-Mat induced a substantial increase in RSV-A neutralization titers in mothers, with efficient transplacental transfer of antibodies that persisted in infants until at least 6 months post-birth.
Conclusion: Consistent with the high titers of transplacentally transferred antibodies, this trial suggests a reduced risk of any/severe MA-RSV-LRTD and RSV hospitalization until 6 months post-birth in infants born to mothers immunized with RSVPreF3-Mat during pregnancy. However, vaccine development was terminated due to an identified preterm birth risk.
{"title":"Efficacy, immunogenicity, and safety of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine.","authors":"Peyman Banooni, Bernard Gonik, Cristina Epalza, Osvaldo Reyes, Shabir A Madhi, Grace Devota Gomez-Go, Khalequ Zaman, Conrado Juan Llapur, Eduardo López-Medina, Thorsten Stanley, Anu Kantele, Li-Min Huang, Marisa Márcia Mussi-Pinhata, Jonas Dewulf, Joanne M Langley, Claudia Seidl, Martin Ota, Martha Kirabo, Bruno Anspach, Ilse Dieussaert, Ouzama Henry, Joon Hyung Kim, Marta Picciolato","doi":"10.1093/cid/ciaf033","DOIUrl":"https://doi.org/10.1093/cid/ciaf033","url":null,"abstract":"<p><strong>Background: </strong>In this phase 3 trial of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine (RSVPreF3-Mat), a higher rate of preterm birth was observed in the vaccine (6.8%) versus the placebo group (4.9%). Trial enrollment and vaccination were stopped. Results of investigations into this safety signal were reported previously. Here, we describe end-of-trial efficacy, immunogenicity, and safety results.</p><p><strong>Methods: </strong>Women 18-49 years old were randomized 2:1 to receive one dose of RSVPreF3-Mat (n=3557) or placebo (n=1771) at 240/7-340/7 weeks' gestation. Primary outcomes were any and severe medically assessed RSV-associated lower respiratory tract disease (MA-RSV-LRTD) in infants until 6 months post-birth and safety until 12 months post-birth. Other efficacy outcomes were evaluated, along with immunogenicity (until 6 months post-partum/birth) and safety in mothers and infants.</p><p><strong>Results: </strong>Efficacy in infants until 6 months post-birth was 65.5% (95% credible interval: 37.5-82.0) against any MA-RSV-LRTD, 69.0% (33.0-87.6) against severe MA-RSV-LRTD, and 50.1% (-3.6-75.8) against RSV hospitalization; it waned over time thereafter. Efficacy against MA-RSV-LRTD was 47.8% (-25.8-77.3) in low- and middle-income and 75.9% (46.1-91.5) in high-income countries. RSVPreF3-Mat induced a substantial increase in RSV-A neutralization titers in mothers, with efficient transplacental transfer of antibodies that persisted in infants until at least 6 months post-birth.</p><p><strong>Conclusion: </strong>Consistent with the high titers of transplacentally transferred antibodies, this trial suggests a reduced risk of any/severe MA-RSV-LRTD and RSV hospitalization until 6 months post-birth in infants born to mothers immunized with RSVPreF3-Mat during pregnancy. However, vaccine development was terminated due to an identified preterm birth risk.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT04605159.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063967","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}
Janvier Serumondo, Peter Barebwanuwe, Ephrem Daniel Sheferaw, Jeannette Iyonizera, Charles Berabose, Sabine Umuraza, Calliope Ntuyenabo, Kelly Reine Kwizera, Donatha Dushimiyimana, Justine Umutesi, Jean Damascene Kabakambira, Bobo Buya, Amy Azania, Caroline E Boeke, Alida Ngwije, Christian B Ramers, Gallican Rwibasira
Sofosbuvir/velpatasvir/voxilaprevir is recommended for hepatitis C virus (HCV) retreatment in those who fail initial treatment but is unavailable in resource-limited settings. We describe a government sofosbuvir/velpatasvir + ribavirin (SOF/VEL + RBV) × 24 weeks retreatment program in Rwanda (November 2021–October 2022). Of 231 participants, 174 were cured (75.3% intention-to-treat analysis). SOF/VEL + RBV may be considered for HCV retreatment in resource-limited settings.
{"title":"Introducing Sofosbuvir/Velpatasvir + Ribavirin as a Generic Retreatment Regimen for Hepatitis C: Evaluation of a Government Program in Rwanda","authors":"Janvier Serumondo, Peter Barebwanuwe, Ephrem Daniel Sheferaw, Jeannette Iyonizera, Charles Berabose, Sabine Umuraza, Calliope Ntuyenabo, Kelly Reine Kwizera, Donatha Dushimiyimana, Justine Umutesi, Jean Damascene Kabakambira, Bobo Buya, Amy Azania, Caroline E Boeke, Alida Ngwije, Christian B Ramers, Gallican Rwibasira","doi":"10.1093/cid/ciae637","DOIUrl":"https://doi.org/10.1093/cid/ciae637","url":null,"abstract":"Sofosbuvir/velpatasvir/voxilaprevir is recommended for hepatitis C virus (HCV) retreatment in those who fail initial treatment but is unavailable in resource-limited settings. We describe a government sofosbuvir/velpatasvir + ribavirin (SOF/VEL + RBV) × 24 weeks retreatment program in Rwanda (November 2021–October 2022). Of 231 participants, 174 were cured (75.3% intention-to-treat analysis). SOF/VEL + RBV may be considered for HCV retreatment in resource-limited settings.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"1 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056616","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}
Roy F Chemaly, Tali Shafat, Anna Wald, Camille N Kotton, Genovefa Papanicolaou, Michelle K Yong, Veronica Miller, Takashi E Komatsu, Charu Mullick, Aimee C Hodowanec, Gabriel Westman, Fareed Khawaja, Alexander Birkmann, Per Ljungman
Herpes simplex virus (HSV) infection is one of the most prevalent viral infections worldwide. In general, host immunity is sufficient to clear viral shedding and recurrences, although it is insufficient to prevent subsequent virologic reactivations. In immunocompromised patients, prolonged and difficult-to-treat HSV infections may develop. The diagnosis of refractory HSV infection is based on the lack of clinical response to nucleoside analogs. Antiviral resistance is confirmed via genotypic and/or phenotypic testing. To provide consensus definitions of refractory and/or resistant (R/R) HSV mucocutaneous infections for clinical trial use, the HSV Resistance Working Group of the Transplant Associated Viral Infections Forum, which includes international clinicians, scientists, industry representatives, and regulatory officials, conducted a literature review of previously published data related to R/R HSV infections in immunocompromised patients. We propose definitions of R/R HSV mucocutaneous infections, which will be subject to re-evaluation and revision based on forthcoming data and future studies.
{"title":"Refractory and Resistant Herpes Simplex Virus Mucocutaneous Infections in Immunocompromised Patients: Literature Review and Proposed Definitions for Use in Clinical Trials","authors":"Roy F Chemaly, Tali Shafat, Anna Wald, Camille N Kotton, Genovefa Papanicolaou, Michelle K Yong, Veronica Miller, Takashi E Komatsu, Charu Mullick, Aimee C Hodowanec, Gabriel Westman, Fareed Khawaja, Alexander Birkmann, Per Ljungman","doi":"10.1093/cid/ciae638","DOIUrl":"https://doi.org/10.1093/cid/ciae638","url":null,"abstract":"Herpes simplex virus (HSV) infection is one of the most prevalent viral infections worldwide. In general, host immunity is sufficient to clear viral shedding and recurrences, although it is insufficient to prevent subsequent virologic reactivations. In immunocompromised patients, prolonged and difficult-to-treat HSV infections may develop. The diagnosis of refractory HSV infection is based on the lack of clinical response to nucleoside analogs. Antiviral resistance is confirmed via genotypic and/or phenotypic testing. To provide consensus definitions of refractory and/or resistant (R/R) HSV mucocutaneous infections for clinical trial use, the HSV Resistance Working Group of the Transplant Associated Viral Infections Forum, which includes international clinicians, scientists, industry representatives, and regulatory officials, conducted a literature review of previously published data related to R/R HSV infections in immunocompromised patients. We propose definitions of R/R HSV mucocutaneous infections, which will be subject to re-evaluation and revision based on forthcoming data and future studies.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"26 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056617","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}
Susan L Ford,Franco Felizarta,Kelong Han,Kehui Wang,Herta Crauwels,Anna Dari,Mar Masia,Miguel Garcia Deltoro,Olaf Degen,Jonathan B Angel,Chiu-Bin Hsiao,Carolina Acuipil,Irina Kolobova,Conn Harrington,Kelly Rimler,William Spreen,Ronald D'Amico
BACKGROUNDCabotegravir + rilpivirine (CAB + RPV) administered via intramuscular gluteal injections is the first complete long-acting regimen for maintaining human immunodeficiency virus type 1 (HIV-1) virologic suppression. We present substudy results on short-term repeat intramuscular CAB + RPV long-acting thigh injections in participants with ≥3 years of experience with gluteal administration during the ATLAS-2M study.METHODSSubstudy phases included screening, thigh injection (day 1-week 16), and return to gluteal injection (week 16-week 24). The injection schedule was unchanged from the main study. Outcomes included pharmacokinetics, safety, tolerability, efficacy, and patient-reported outcomes. Pharmacokinetic parameters were determined using noncompartmental analysis and mixed-effects modeling. Population pharmacokinetic simulations were performed.RESULTSThere were 118 participants. In the arm that received injections every 2 months (Q2M), first CAB thigh injection including area under the concentration-time curve and maximum observed concentration (Cmax) and first RPV thigh injection Cmax and all last RPV thigh injection parameters were statistically higher vs gluteal injections (paired comparison). No significant differences occurred with once-monthly (QM) dosing. No participants had HIV-1 RNA ≥50 copies/mL after thigh injections. Overall, 4%-7% of injection site reactions (ISRs) were grade 3. Five participants withdrew due to an ISR or injection intolerability. Overall, 30% preferred thigh vs gluteal injections. Simulations demonstrated the potential for chronic/continuous QM or ≤2 consecutive Q2M thigh injections.CONCLUSIONSThese data demonstrate the potential use of chronic/continuous QM and rotational/short-term QM or Q2M (≤4 months of continuous dosing), CAB + RPV long-acting intramuscular thigh administration for HIV-1 treatment.
{"title":"Thigh Injections of Cabotegravir + Rilpivirine in Virally Suppressed Adults With Human Immunodeficiency Virus Type 1: A Substudy of the Phase 3b ATLAS-2M Study.","authors":"Susan L Ford,Franco Felizarta,Kelong Han,Kehui Wang,Herta Crauwels,Anna Dari,Mar Masia,Miguel Garcia Deltoro,Olaf Degen,Jonathan B Angel,Chiu-Bin Hsiao,Carolina Acuipil,Irina Kolobova,Conn Harrington,Kelly Rimler,William Spreen,Ronald D'Amico","doi":"10.1093/cid/ciae620","DOIUrl":"https://doi.org/10.1093/cid/ciae620","url":null,"abstract":"BACKGROUNDCabotegravir + rilpivirine (CAB + RPV) administered via intramuscular gluteal injections is the first complete long-acting regimen for maintaining human immunodeficiency virus type 1 (HIV-1) virologic suppression. We present substudy results on short-term repeat intramuscular CAB + RPV long-acting thigh injections in participants with ≥3 years of experience with gluteal administration during the ATLAS-2M study.METHODSSubstudy phases included screening, thigh injection (day 1-week 16), and return to gluteal injection (week 16-week 24). The injection schedule was unchanged from the main study. Outcomes included pharmacokinetics, safety, tolerability, efficacy, and patient-reported outcomes. Pharmacokinetic parameters were determined using noncompartmental analysis and mixed-effects modeling. Population pharmacokinetic simulations were performed.RESULTSThere were 118 participants. In the arm that received injections every 2 months (Q2M), first CAB thigh injection including area under the concentration-time curve and maximum observed concentration (Cmax) and first RPV thigh injection Cmax and all last RPV thigh injection parameters were statistically higher vs gluteal injections (paired comparison). No significant differences occurred with once-monthly (QM) dosing. No participants had HIV-1 RNA ≥50 copies/mL after thigh injections. Overall, 4%-7% of injection site reactions (ISRs) were grade 3. Five participants withdrew due to an ISR or injection intolerability. Overall, 30% preferred thigh vs gluteal injections. Simulations demonstrated the potential for chronic/continuous QM or ≤2 consecutive Q2M thigh injections.CONCLUSIONSThese data demonstrate the potential use of chronic/continuous QM and rotational/short-term QM or Q2M (≤4 months of continuous dosing), CAB + RPV long-acting intramuscular thigh administration for HIV-1 treatment.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":"74 1","pages":""},"PeriodicalIF":11.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057059","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}
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