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Peer AD, Price JC. Update on hepatitis C virus management. Curr Opin Gastroenterol 2025:00001574-990000000-00190. [PMID: 40227981 DOI: 10.1097/mog.0000000000001098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/16/2025]
Abstract
PURPOSE OF REVIEW Despite the efficacy of direct-acting antiviral (DAA) therapy, hepatitis C virus (HCV) remains a significant contributor to liver-related morbidity and mortality. This review summarizes the approach to HCV treatment, the simplified treatment algorithm for most patients, the management of special populations, and future directions for HCV interventions. RECENT FINDINGS Pan genotypic DAA regimens have high cure rates and can be managed by nonspecialist providers, and the simplified treatment approach provides a clear algorithm for workup and treatment decisions among treatment-naive patients without decompensated cirrhosis. Additionally, advancements in point of care diagnostics have the potential to further expand access to screening and linkage to care. Despite these breakthroughs, barriers to accessing care and the stigmatization of high-risk populations continue to undercut progress towards HCV elimination. Continued implementation of innovative screening and treatment strategies are required to overcome rising HCV prevalence. SUMMARY HCV cure is achievable for nearly all patients, but reaching HCV elimination goals will require a comprehensive approach that increases screening, expands access to simplified treatment, and avoids stigmatization of at-risk populations. Targeting healthcare disparities and removing barriers to treatment uptake are crucial to achieving elimination targets.
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Affiliation(s)
- Austin D Peer
- Department of Medicine, University of California, San Francisco, San Francisco, California, USA
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2
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Ma J, Nance RM, Cachay E, Ruderman SA, Kitahata M, Falade-Nwulia O, Chander G, Drumright LN, Hurt CB, Yendewa GA, Pettit A, Moore RD, Fredericksen RJ, Lloyd A, Bamford L, Napravnik S, Fleming J, Christopoulos K, Burkholder G, Keruly J, Delaney JAC, Crane H, Kim HN. Prevalence and Correlates of Hepatitis C Viremia Among People With Human Immunodeficiency Virus in the Direct-Acting Antiviral Era. Open Forum Infect Dis 2025; 12:ofaf030. [PMID: 39896988 PMCID: PMC11786118 DOI: 10.1093/ofid/ofaf030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 01/16/2025] [Indexed: 02/04/2025] Open
Abstract
Background National US data on the burden and risks for hepatitis C virus (HCV) infection in people with human immunodeficiency virus (HIV) during the direct-acting antiviral (DAA) era are limited. These data are important to understand current progress and guide future efforts toward HCV microelimination. Methods We evaluated (1) HCV prevalence (2011-2013, 2014-2017, 2018-2022) using a serial cross-sectional design and (2) correlates for HCV viremia (2018-2022) in adult people with HIV (PWH) within the Centers for AIDS Research Network of Integrated Clinic Systems (CNICS) cohort using multivariable adjusted relative risk regression. The most recent data from each time period were used for calculations and models. Results In the CNICS cohort, HCV viremia prevalence was 8.7% in 2011-2013, 10.5% in 2014-2017, and 4.8% in 2018-2022. Disparities in prevalence across demographic groups defined by age, gender, and race/ethnicity were smaller in 2018-2022 than earlier time periods. In relative risk regression, female gender, detectable HIV RNA, higher proportion of missed visits (last 18 months), higher FIB-4 score, higher depressive symptom severity, and current use of methamphetamine and illicit opioids were associated with HCV viremia in 2018-2022. Conclusions The prevalence of HCV viremia during the DAA era in this US-based national cohort of PWH improved over time and across demographic subgroups but remains higher than those without HIV. Our findings highlight the continued importance of prioritizing HCV care in all PWH, especially in certain key, less-reached groups. Proactive, comprehensive efforts to care engagement, substance use, mental health, and other social determinants will be crucial to improve reach, prevention, and treatment to achieve HCV elimination goals.
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Affiliation(s)
- Jimmy Ma
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Robin M Nance
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Edward Cachay
- Department of Medicine, University of California, San Diego, San Diego, California, USA
| | | | - Mari Kitahata
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Oluwaseun Falade-Nwulia
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Geetanjali Chander
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Lydia N Drumright
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Christopher B Hurt
- Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - George A Yendewa
- Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
| | - April Pettit
- Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA
| | - Richard D Moore
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Rob J Fredericksen
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Audrey Lloyd
- Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Laura Bamford
- Department of Medicine, University of California, San Diego, San Diego, California, USA
| | - Sonia Napravnik
- Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Julia Fleming
- The Fenway Institute, Fenway Health, Boston, Massachusetts, USA
| | - Katerina Christopoulos
- Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Greer Burkholder
- Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Jeanne Keruly
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Joseph A C Delaney
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - Heidi Crane
- Department of Medicine, University of Washington, Seattle, Washington, USA
| | - H Nina Kim
- Department of Medicine, University of Washington, Seattle, Washington, USA
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Harney BL, Sacks‐Davis R, van Santen DK, Stewart AC, Matthews GV, Carson JM, Klein MB, Lacombe K, Wittkop L, Salmon D, Leleux O, Merchadou L, van der Valk M, Smit C, Prins M, Boyd A, Berenguer J, Jarrin I, Rauch A, Hellard ME, Doyle JS. Unsuccessful Direct Acting Antiviral Hepatitis C Treatment Among People With HIV: Findings From an International Cohort. Liver Int 2025; 45:1-13. [PMID: 39656170 PMCID: PMC11629931 DOI: 10.1111/liv.16203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 10/29/2024] [Accepted: 11/26/2024] [Indexed: 12/12/2024]
Abstract
BACKGROUND Historically, hepatitis C virus (HCV) was difficult to treat among people with HIV. However, treatment with direct-acting antivirals (DAAs) results in 90%-95% of people being cured. There is a need to understand why a proportion of people are not cured. We aimed to examine characteristics that may indicate an increased probability of unsuccessful DAA HCV treatment. METHODS Data were from the International Collaboration on Hepatitis C Elimination in HIV Cohorts. People who commenced DAA HCV treatment between 2014 and 2019 were included. Unsuccessful treatment was defined as a positive HCV RNA test at a person's first RNA test at least 4 weeks (SVR4+) following the end of treatment. Multivariable mixed-effects logistic regression was used to examine characteristics associated with unsuccessful treatment. RESULTS Of 4468 people who commenced DAA treatment, 4098 (91.7%) had an SVR test 4+ weeks following the end of treatment, 207 (5%) of whom were unsuccessfully treated. Compared to a CD4+ cell count > 500 cells/mm3, cell counts < 200 (aOR 1.81, 95%CI 1.00-3.29) and between 200 and 349 (aOR 1.95, 95%CI 1.30-2.93) were associated with increased odds of unsuccessful treatment. Among 1921 people with data on injection drug use in the 12 months prior to treatment, there was some evidence that recent injection drug use was associated with increased odds of unsuccessful treatment; however, this was not statistically significant (aOR 1.67, 95%CI 0.99-2.82). CONCLUSIONS The overwhelming majority of people were successfully treated for HCV. Overall, 5% of those with an SVR4+ test were unsuccessfully treated; this was more likely among people with evidence of immunodeficiency and those who reported recently injecting drugs.
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Affiliation(s)
- Brendan L. Harney
- Disease Elimination ProgramBurnet InstituteMelbourneAustralia
- School of Public Health and Preventive MedicineMonash UniversityMelbourneAustralia
- Department of Infectious DiseasesAlfred Health and Monash UniversityMelbourneAustralia
| | - Rachel Sacks‐Davis
- Disease Elimination ProgramBurnet InstituteMelbourneAustralia
- School of Public Health and Preventive MedicineMonash UniversityMelbourneAustralia
- School of Population and Global HealthUniversity of MelbourneMelbourneAustralia
| | - Daniela K. van Santen
- Disease Elimination ProgramBurnet InstituteMelbourneAustralia
- Department of Infectious Diseases, Research and PreventionPublic Health Service of AmsterdamAmsterdamThe Netherlands
| | - Ashleigh C. Stewart
- Disease Elimination ProgramBurnet InstituteMelbourneAustralia
- School of Public Health and Preventive MedicineMonash UniversityMelbourneAustralia
| | - Gail V. Matthews
- The Kirby Institute UNSWSydneyAustralia
- St Vincent's HospitalSydneyAustralia
| | | | - Marina B. Klein
- Division of Infectious Diseases and Chronic Viral Illness Service, Department of MedicineMcGill University Health CentreMontrealCanada
| | - Karine Lacombe
- Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé PubliqueParisFrance
- Service de Maladies InfectieusesHôpital Saint‐Antoine APHPParisFrance
| | - Linda Wittkop
- CHU Bordeaux, Service d'information médicaleBordeauxFrance
- University of Bordeaux, INSERM, Bordeaux Population Health Research Centre U1219, CIC‐ECBordeauxFrance
- INRIA SISTM TeamTalenceFrance
| | - Dominque Salmon
- Université Paris Descartes, Service Maladies Infectieuses et Tropicales, AP‐HP, Hôpital CochinParisFrance
| | - Olivier Leleux
- University of Bordeaux, INSERM, Bordeaux Population Health Research Centre U1219, CIC‐ECBordeauxFrance
| | - Laurence Merchadou
- University of Bordeaux, INSERM, Bordeaux Population Health Research Centre U1219, CIC‐ECBordeauxFrance
| | - Marc van der Valk
- Department of Infectious DiseasesAmsterdam University Medical Centers, University of AmsterdamAmsterdamNetherlands
- Amsterdam Infection & Immunity Institute, Amsterdam University Medical Centers, University of AmsterdamAmsterdamThe Netherlands
- Stichting HIV MonitoringAmsterdamThe Netherlands
| | - Colette Smit
- Stichting HIV MonitoringAmsterdamThe Netherlands
| | - Maria Prins
- Department of Infectious Diseases, Research and PreventionPublic Health Service of AmsterdamAmsterdamThe Netherlands
- Department of Infectious DiseasesAmsterdam University Medical Centers, University of AmsterdamAmsterdamNetherlands
- Amsterdam Infection & Immunity Institute, Amsterdam University Medical Centers, University of AmsterdamAmsterdamThe Netherlands
| | - Anders Boyd
- Department of Infectious Diseases, Research and PreventionPublic Health Service of AmsterdamAmsterdamThe Netherlands
- Amsterdam Infection & Immunity Institute, Amsterdam University Medical Centers, University of AmsterdamAmsterdamThe Netherlands
- Stichting HIV MonitoringAmsterdamThe Netherlands
| | - Juan Berenguer
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC)MadridSpain
- Infectious Diseases, Hospital General Universitario Gregorio Marañón (IsSGM)MadridSpain
- Instituto de Salud Carlos IIIMadridSpain
| | - Inmaculada Jarrin
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC)MadridSpain
- Infectious Diseases, Hospital General Universitario Gregorio Marañón (IsSGM)MadridSpain
- Instituto de Salud Carlos IIIMadridSpain
| | - Andri Rauch
- Department of Infectious DiseasesInselspital, Bern University Hospital, University of BernBernSwitzerland
| | - Margaret E. Hellard
- Disease Elimination ProgramBurnet InstituteMelbourneAustralia
- School of Public Health and Preventive MedicineMonash UniversityMelbourneAustralia
- Department of Infectious DiseasesAlfred Health and Monash UniversityMelbourneAustralia
- Doherty Institute and School of Population and Global HealthUniversity of MelbourneMelbourneAustralia
| | - Joseph S. Doyle
- Disease Elimination ProgramBurnet InstituteMelbourneAustralia
- School of Public Health and Preventive MedicineMonash UniversityMelbourneAustralia
- Department of Infectious DiseasesAlfred Health and Monash UniversityMelbourneAustralia
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Fierer DS, Carollo JR, Rodriguez-Caprio G, Radix A, Vail R, Chavez R, Bungay KJ, Dillon SM. Hepatitis C Virus Reinfection Among Men Who Have Sex With Men With HIV in New York City. Clin Infect Dis 2024; 79:1420-1427. [PMID: 39023296 DOI: 10.1093/cid/ciae297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Indexed: 07/20/2024] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) reinfection rates are substantially higher than primary infection rates among men who have sex with men (MSM) with human immunodeficiency virus (HIV) in European cohorts. The behaviors mediating this high rate of transmission among MSM are poorly characterized. METHODS We performed a prospective cohort study in New York City (NYC) of MSM with HIV who cleared HCV to determine the incidence of and risk factors for HCV reinfection. We assessed the risk behaviors for primary HCV in NYC: receipt of semen in the rectum, and sexualized methamphetamine use, along with route of use. Multivariable analysis was performed with Andersen-Gill extension of the Cox proportional hazards model. RESULTS From 2000 through 2018, among 304 MSM with HIV who cleared HCV, 42 reinfections occurred over 898 person-years, for an incidence rate of 4.7 per 100 person-years. Assessing 1245 postclearance visits, only receipt of semen into the rectum was associated with reinfection (hazard ratio, 9.7 [95% confidence interval: 3.3-28.3], P < .001); methamphetamine use was not. CONCLUSIONS The high HCV reinfection rate over almost 2 decades demonstrates that sexual transmission of HCV is not inefficient or unusual and that direct-acting antiviral treatment is not sufficient for HCV elimination among MSM in NYC. The contrasts between both the rates of and risk factors for primary and HCV reinfection suggest that HCV prevalence is highly heterogenous among sexual networks and that sexualized methamphetamine use, rather than mediating transmission, is instead a surrogate marker for the highest HCV prevalence networks. As neither condoms nor treatment have been successful strategies for HCV prevention in NYC, novel interventions are needed to stem this sexually transmitted HCV epidemic.
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Affiliation(s)
- Daniel S Fierer
- Icahn School of Medicine at Mount Sinai, Department of Medicine, Division of Infectious Diseases, New York, New York, USA
| | - Jesse R Carollo
- Icahn School of Medicine at Mount Sinai, Department of Medicine, Division of Infectious Diseases, New York, New York, USA
| | - Gabriela Rodriguez-Caprio
- Icahn School of Medicine at Mount Sinai, Department of Medicine, Division of Infectious Diseases, New York, New York, USA
| | - Asa Radix
- Callen-Lorde Community Health Center, Department of Medicine, New York, New York, USA
| | - Rona Vail
- Callen-Lorde Community Health Center, Department of Medicine, New York, New York, USA
| | - Robert Chavez
- NYU Grossman School of Medicine, Department of Medicine, New York, New York, USA
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Shabil M, Yadav A, Shamim MA, Ahmed M, Satapathy P, Zaidan AA, Khatib MN, Gaidhane S, Zahiruddin QS, Rabaan AA, Al Kaabi NA, Almosa FAM, AlSihati J, Sah R. Prevalence of hepatitis B and C infections among HIV-positive men who have sex with men: A systematic review and meta-analysis. Health Sci Rep 2024; 7:e2206. [PMID: 38933421 PMCID: PMC11199987 DOI: 10.1002/hsr2.2206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2023] [Revised: 05/10/2024] [Accepted: 06/06/2024] [Indexed: 06/28/2024] Open
Abstract
Background Human immunodeficiency virus (HIV) infection is highly prevalent and often coexists with other infectious diseases, especially Hepatitis B virus (HBV) and Hepatitis C virus (HCV). Men who have sex with men (MSM) represent a vulnerable population in terms of HIV infection. We aimed to determine the prevalence of HCV, HBV among HIV-infected MSM. Methods This systematic review and meta-analysis searched PubMed, Cochrane, Scopus, Web of Science, and ProQuest up-to 2023/04/22. All studies reporting the prevalence of HBV or HCV infection in MSM PLHIV were included. Meta-analysis used random effect model for synthesis and I 2 along with prediction interval for heterogeneity. Subgroup analysis based on continent and meta-regression for study size, average age and year of publication were used to explore heterogeneity. Modified Newcastle-Ottawa Scale was used to evaluate the quality of studies according to the protocol (PROSPERO: CRD42023428764). Results Fifty-six of 5948 studies are included. In 53 studies with 3,07,589 participants, a pooled prevalence of 7% (95% confidence interval [CI]: 5-10) was found for HCV among MSM PLHIV, while a 9% (95% CI: 4-18) prevalence was found for HBV infection from five studies which included 5641 MSM PLHIV. Asia reported the lowest pooled prevalence at 5.84% (95% CI: 2.98-11.13) for HCV while Europe reported the highest pooled prevalence at 7.76% (95% CI: 4.35-13.45). Baujat plot and influence diagnostic identified contributors to influence and between-study heterogeneity. Sensitivity analyses omitting these studies result in considerably more precise estimates. Another sensitivity analysis as leave-one-out meta-analysis did not change any pooled estimate significantly. Conclusion There is a significant burden of HCV and HBV among MSM PLHIV worldwide, with varying prevalence rates. Future studies should focus on these multimorbidity clusters and investigate factors influencing disease burden, long-term outcomes, optimal testing strategies, and tailored interventions.
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Affiliation(s)
- Muhammed Shabil
- Evidence of Policy and LearningGlobal Center for Evidence SynthesisChandigarhIndia
| | - Aarti Yadav
- Evidence of Policy and LearningGlobal Center for Evidence SynthesisChandigarhIndia
| | - Muhammed A. Shamim
- Department of PharmacologyAll India Institute of Medical SciencesJodhpurIndia
| | - Mohammed Ahmed
- School of Medical SciencesUniversity of HyderabadHyderabadIndia
| | - Prakasini Satapathy
- Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical SciencesSaveetha UniversityChennaiIndia
- Medical Laboratories Techniques DepartmentAL‐Mustaqbal UniversityHillahBabilIraq
| | - Ali A. Zaidan
- Gastroenterology DepartmentKing Fahad Armed Forces HospitalJeddahSaudi Arabia
| | - Mahalaqua N. Khatib
- Division of Evidence Synthesis, Global Consortium of Public Health and ResearchDatta Meghe Institute of Higher EducationWardhaIndia
| | - Shilpa Gaidhane
- One Health Centre (COHERD), Jawaharlal Nehru Medical CollegeDatta Meghe Institute of Higher EducationWardhaIndia
| | - Quazi S. Zahiruddin
- Global Health Academy, Division of Evidence Synthesis, School of Epidemiology and Public Health and Research, Jawaharlal Nehru Medical CollegeInstitute of Higher education and ResearchWardhaIndia
| | - Ali A. Rabaan
- Molecular Diagnostic LaboratoryJohns Hopkins Aramco HealthcareDhahranSaudi Arabia
- College of MedicineAlfaisal UniversityRiyadhSaudi Arabia
- Department of Public Health and NutritionThe University of HaripurHaripurPakistan
| | - Nawal A. Al Kaabi
- College of Medicine and Health ScienceKhalifa UniversityAbu DhabiUnited Arab Emirates
- Sheikh Khalifa Medical CityAbu Dhabi Health Services Company (SEHA)Abu DhabiUnited Arab Emirates
| | - Fadel A. M. Almosa
- Gastroenterology Unit, Department of Internal Medicine, Qatif Central HospitalMinistry of HealthQatifSaudi Arabia
| | - Jehad AlSihati
- Internal Medicine Department, Gastroenterology SectionKing Fahad Specialist HospitalDammamSaudi Arabia
| | - Ranjit Sah
- Department of MicrobiologyTribhuvan University Teaching HospitalKathmanduNepal
- Department of Clinical Microbiology, DY Patil Medical College, Hospital and Research CentreDY Patil VidyapeethPuneMaharashtraIndia
- Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and HospitalDr. D.Y. Patil VidyapeethPuneMaharashtraIndia
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Basyte-Bacevice V, Kupcinskas L. Viral Hepatitis C: From Unraveling the Nature of Disease to Cure and Global Elimination. Dig Dis 2024; 42:486-495. [PMID: 38718765 DOI: 10.1159/000539210] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 04/23/2024] [Indexed: 06/13/2024]
Abstract
BACKGROUND The discovery of the hepatitis C virus (HCV) and direct-acting antiviral (DAA) drugs is one of the major milestones in the last 3 decades of medicine. These discoveries encouraged the World Health Organization (WHO) to set an ambitious goal to eliminate HCV by 2030, meaning "a 90% reduction in new cases of chronic HCV, a 65% reduction in HCV deaths, and treatment of 80% of eligible people with HCV infections." SUMMARY This review summarizes the key achievements from the discovery of HCV to the development of effective treatment and global elimination strategies. A better understanding of HCV structure, enzymes, and lifecycle led to the introduction of new drug targets and the discovery of DAA. Massive public health interventions are required, such as screening, access to care, treatment, and post-care follow-up, to make the most of DAA's potential. Screening must be supported by fast, accessible, sensitive, specific HCV diagnostic tests and noninvasive methods to determine the stage of liver disease. Linkage to care and treatment access are critical components of a comprehensive HCV elimination program, and decentralization plays a key role in ensuring their effectiveness. KEY MESSAGES Effective and simple screening strategies, rapid diagnostic tools, linkage to health care, and accessible treatment are key elements to achieving the WHO's goal. Incorporating treatment as prevention strategies into elimination programs together with preventive education and harm reduction interventions can have a profound and lasting impact on reducing both the incidence and prevalence of HCV. However, WHO's goal can be challenging to implement because of the need for high financial resources and strong political commitment.
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Affiliation(s)
| | - Limas Kupcinskas
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
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Chromy D, Mandorfer M. Are reinfections undermining HCV elimination efforts? Lancet HIV 2024; 11:e68-e69. [PMID: 38224709 DOI: 10.1016/s2352-3018(23)00309-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Accepted: 11/20/2023] [Indexed: 01/17/2024]
Affiliation(s)
- David Chromy
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna 1090, Austria; Department of Dermatology, Medical University of Vienna, Vienna 1090, Austria
| | - Mattias Mandorfer
- Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna 1090, Austria.
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Chen P, Simonetto DA, Paul S, Patel A. Health disparities experienced by sexual and gender minority individuals living with or at risk of chronic liver disease. Clin Liver Dis (Hoboken) 2023; 22:152-156. [PMID: 37908866 PMCID: PMC10615390 DOI: 10.1097/cld.0000000000000073] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 04/28/2023] [Indexed: 11/02/2023] Open
Affiliation(s)
- Phillip Chen
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Douglas A. Simonetto
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Sonali Paul
- Department of Gastroenterology, Hepatology, and Nutrition, Center for Liver Diseases, The University of Chicago Medicine, Chicago, Illinois, USA
| | - Arpan Patel
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
- Department of Gastroenterology, Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
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Tsai WC, Chiang HC, Chiu YC, Chien SC, Cheng PN, Chiu HC. Chronic Hepatitis C Virus Infection: An Ongoing Challenge in Screening and Treatment. Life (Basel) 2023; 13:1964. [PMID: 37895346 PMCID: PMC10608250 DOI: 10.3390/life13101964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 09/22/2023] [Accepted: 09/23/2023] [Indexed: 10/29/2023] Open
Abstract
With the advent of direct-acting antiviral agents (DAA) in the recent few years, hepatitis C virus (HCV) infection has become a curable infectious disease. Successful clearance of HCV could lead to improvement of both hepatic and extrahepatic outcomes, such as complications of cirrhosis, hepatocellular carcinoma, cardiovascular diseases, and incident diabetes. However, challenges persist in reaching the HCV elimination goals of the World Health Organization by 2030. Among these challenges are identifying those already infected or undiagnosed subjects, re-linking to the care of known but untreated HCV-infected subjects, and developing strategies to enhance treatment rates and compliance in specific or high-risk populations. In addition, issues of post-DAA viral clearance, including avoiding or preventing reinfection in high-risk populations and surveillance of hepatocellular carcinoma, are important to consolidate the treatment's short- and long-term efficacies. In the current DAA era, treatment is the most effective prevention strategy not only in its excellent efficacy and safety but also in preventing HCV spread. All of the surveillance or measures should center on DAA treatment in clinical practice.
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Affiliation(s)
| | | | | | | | - Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; (W.-C.T.); (H.-C.C.); (Y.-C.C.); (S.-C.C.)
| | - Hung-Chih Chiu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan; (W.-C.T.); (H.-C.C.); (Y.-C.C.); (S.-C.C.)
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10
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Martinello M, Solomon SS, Terrault NA, Dore GJ. Hepatitis C. Lancet 2023; 402:1085-1096. [PMID: 37741678 DOI: 10.1016/s0140-6736(23)01320-x] [Citation(s) in RCA: 66] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 05/30/2023] [Accepted: 06/22/2023] [Indexed: 09/25/2023]
Abstract
Hepatitis C virus (HCV) is a hepatotropic RNA virus that can cause acute and chronic hepatitis, with progressive liver damage resulting in cirrhosis, decompensated liver disease, and hepatocellular carcinoma. In 2016, WHO called for the elimination of HCV infection as a public health threat by 2030. Despite some progress, an estimated 57 million people were living with HCV infection in 2020, and 300 000 HCV-related deaths occur per year. The development of direct-acting antiviral therapy has revolutionised clinical care and generated impetus for elimination, but simplified and broadened HCV screening, enhanced linkage to care, and higher coverage of treatment and primary prevention strategies are urgently required.
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Affiliation(s)
- Marianne Martinello
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia; Department of Infectious Diseases, Prince of Wales Hospital, Sydney, NSW, Australia.
| | - Sunil S Solomon
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Norah A Terrault
- Division of Gastrointestinal and Liver Diseases, University of Southern California, Los Angeles, CA, USA
| | - Gregory J Dore
- Viral Hepatitis Clinical Research Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia; Department of Infectious Diseases, St Vincent's Hospital, Sydney, NSW, Australia
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11
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Huang CF, Chen GJ, Hung CC, Yu ML. HCV Microelimination for High-risk Special Populations. J Infect Dis 2023; 228:S168-S179. [PMID: 37703340 DOI: 10.1093/infdis/jiac446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/15/2023] Open
Abstract
The World Health Organization has set tremendous goals to eliminate viral hepatitis by 2030. However, most countries are currently off the track for achieving these goals. Microelimination is a more effective and practical approach that breaks down national elimination targets into goals for smaller and more manageable key populations. These key populations share the characteristics of being highly prevalent for and vulnerable to hepatitis C virus (HCV) infection. Microelimination allows for identifying HCV-infected people and linking them to care more cost-effectively and efficiently. In this review, we discuss the current obstacles to and progress in HCV microelimination in special populations, including uremic patients undergoing hemodialysis, people who inject drugs, incarcerated people, people living in hyperendemic areas, men who have sex with men with or without human immunodeficiency virus (HIV) infection, transgender and gender-diverse populations, and sex workers. Scaling up testing and treatment uptake to achieve HCV microelimination may facilitate global HCV elimination by 2030.
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Affiliation(s)
- Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital and College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- PhD Program in Translational Medicine, College of Medicine, Kaohsiung Medical University, Academia Sinica, Kaohsiung, Taiwan
- Faculty of Internal Medicine and Hepatitis Research Center, College of Medicine, and Center for Cohort Study, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Guan-Jhou Chen
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College Medicine, Taipei, Taiwan
- Min-Sheng General Hospital, Taoyuan, Taiwan
| | - Chien-Ching Hung
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College Medicine, Taipei, Taiwan
- Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
- Department of Medicine, China Medical University, Taichung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital and College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
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12
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Bhattacharya D, Aronsohn A, Price J, Lo Re V. Hepatitis C Guidance 2023 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection. Clin Infect Dis 2023:ciad319. [PMID: 37229695 DOI: 10.1093/cid/ciad319] [Citation(s) in RCA: 84] [Impact Index Per Article: 42.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 05/11/2023] [Accepted: 05/23/2023] [Indexed: 05/27/2023] Open
Abstract
The Infectious Diseases Society of America and the American Association for the Study of Liver Diseases have collaboratively developed evidence-based guidance regarding the diagnosis, management, and treatment of hepatitis C virus (HCV) infection since 2013. A panel of clinicians and investigators with extensive infectious diseases or hepatology expertise specific to HCV infection periodically review evidence from the field and update existing recommendations or introduce new recommendations as evidence warrants. This update focuses on changes to the guidance since the previous 2020 published update, including ongoing emphasis on recommended universal screening; management recommendations for incomplete treatment adherence; expanded eligibility for simplified chronic HCV infection treatment in adults with minimal monitoring; updated treatment and retreatment recommendations for children as young as 3 years old; management and treatment recommendations in the transplantation setting; and screening, treatment, and management recommendations for unique and key populations.
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Affiliation(s)
- Debika Bhattacharya
- Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine at UCLA
| | - Andrew Aronsohn
- Department of Medicine, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago
| | - Jennifer Price
- Division of Medicine, Department of Gastroenterology and Hepatology, University of California, San Francisco
| | - Vincent Lo Re
- Department of Medicine, Division of Infectious Diseases and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine
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13
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Isfordink CJ, Boyd A, Sacks-Davis R, van Santen DK, Smit C, Martinello M, Stoove M, Berenguer J, Wittkop L, Klein MB, Rauch A, Salmon D, Lacombe K, Stewart A, Schinkel J, Doyle JS, Hellard M, van der Valk M, Matthews GV. Reasons for not commencing direct-acting antiviral treatment despite unrestricted access for individuals with HIV and hepatitis C virus: a multinational, prospective cohort study. Lancet Public Health 2023; 8:e294-e304. [PMID: 36965984 DOI: 10.1016/s2468-2667(23)00056-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 01/23/2023] [Accepted: 02/27/2023] [Indexed: 03/27/2023]
Abstract
BACKGROUND Individuals with HIV and hepatitis C virus (HCV) who remain untreated with direct-acting antivirals can contribute to HCV transmission and HCV-related mortality. We aimed to compare rates of uptake of direct-acting antivirals following unrestricted access to this treatment in high-income countries and examine factors associated with remaining untreated. METHODS This multinational, prospective cohort study used data from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC). We analysed data from nine observational cohorts participating in the InCHEHC, including data from six high-income countries (Australia, Canada, France, the Netherlands, Spain, and Switzerland). We included individuals aged 18 years and older, with HIV and HCV (ie, HCV-RNA positive without evidence of spontaneous clearance) during unrestricted access to interferon-free direct-acting antiviral treatment in each country. We calculated the cumulative proportion of participants who remained untreated with direct-acting antivirals, with follow-up starting after the date of unrestricted access or cohort inclusion, whichever occurred most recently. Factors associated with the commencement rate of direct-acting antiviral treatment were assessed using competing-risks regression with the Fine-Gray method. FINDINGS The date of unrestricted access to direct-acting antiviral treatment for people with HIV ranged from Nov 1, 2014, in France to Nov 1, 2017, in Switzerland. We included 4552 individuals with HIV-HCV, mainly men who have sex with men (MSM; n=2156 [47%]) and people who inject or have injected drugs (n=1453 [32%]). 1365 (30%) of 4552 participants remained untreated with direct-acting antivirals. For individuals treated with direct-acting antivirals, median time from start of follow-up to treatment was 5 months (IQR 2-12). For individuals who were not treated with direct-acting antivirals, median follow-up was 22 months (8-30). Being linked to care in Australia, France, or the Netherlands, on antiretroviral therapy, having undetectable HIV RNA, and shorter duration since first positive HCV test were independently associated with higher commencement rate of direct-acting antiviral treatment. Compared with MSM, male heterosexuals and females with unknown or other routes of HIV transmission (ie, neither injection drug use nor heterosexual transmission) had lower rates of commencement. INTERPRETATION Despite unrestricted access, almost a third of individuals with HIV-HCV remained untreated with direct-acting antivirals during follow-up, with variation in commencement rate of HCV treatment between countries and key populations. Increased efforts are required to reach the remaining individuals with HIV who are HCV-viraemic to achieve HIV-HCV micro-elimination. FUNDING None.
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Affiliation(s)
- Cas J Isfordink
- Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
| | - Anders Boyd
- Stichting HIV Monitoring, Amsterdam, Netherlands; Department of Infectious Diseases, Research, and Prevention, Public Health Service of Amsterdam, Amsterdam, Netherlands
| | - Rachel Sacks-Davis
- Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Doherty Institute and School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia
| | - Daniela K van Santen
- Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands; Department of Infectious Diseases, Research, and Prevention, Public Health Service of Amsterdam, Amsterdam, Netherlands; Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia
| | - Colette Smit
- Stichting HIV Monitoring, Amsterdam, Netherlands
| | | | - Mark Stoove
- Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia; School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia
| | - Juan Berenguer
- Infectious Diseases, Hospital General Universitario Gregorio Marañón (IiSGM), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain
| | - Linda Wittkop
- University of Bordeaux, INSERM, Institut Bergonié, BPH, U1219, CIC-EC 1401, Bordeaux, France; INRIA, Talence, France; CHU de Bordeaux, Service d'Information Médicale, INSERM, Institut Bergonié, CIC-EC 1401, Bordeaux, France
| | - Marina B Klein
- Division of Infectious Diseases and Chronic Viral Illness Service, Department of Medicine, McGill University Health Centre, Montreal, QC, Canada
| | - Andri Rauch
- Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Dominique Salmon
- Service Maladies Infectieuses et Tropicales, AP-HP Centre, Hôspital Cochin Hôtel Dieu, Paris, France
| | - Karine Lacombe
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, IPLESP, Paris, France
| | - Ashleigh Stewart
- Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia
| | - Janke Schinkel
- Department of Medical Microbiology and Infection Prevention, Section of Clinical Virology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands
| | - Joseph S Doyle
- Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia; Department of Infectious Diseases, The Alfred Hospital, Melbourne, VIC, Australia
| | - Margaret Hellard
- Disease Elimination Program, Burnet Institute, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Doherty Institute and School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia; Department of Infectious Diseases, The Alfred Hospital, Melbourne, VIC, Australia
| | - Marc van der Valk
- Department of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands; Stichting HIV Monitoring, Amsterdam, Netherlands.
| | - Gail V Matthews
- Kirby Institute, University of New South Wales, Sydney, NSW, Australia
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14
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Maasoumy B, Ingiliz P, Spinner CD, Cordes C, Stellbrink HJ, Schulze zur Wiesch J, Schneeweiß SM, Deterding K, Müller T, Kahlhöfer J, Dörge P, von Karpowitz M, Manns MP, Wedemeyer H, Cornberg M. Sofosbuvir plus velpatasvir for 8 weeks in patients with acute hepatitis C: The HepNet acute HCV-V study. JHEP Rep 2023; 5:100650. [PMID: 36852107 PMCID: PMC9957891 DOI: 10.1016/j.jhepr.2022.100650] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 12/01/2022] [Accepted: 12/05/2022] [Indexed: 12/23/2022] Open
Abstract
Background & Aims EASL guidelines recommend 8 weeks of treatment with sofosbuvir plus velpatasvir (SOF/VEL) for the treatment of acute or recently acquired HCV infection, but only 6- and 12-week data are available. Therefore, the aim of this study was to evaluate the safety and efficacy of a shortened 8-week SOF/VEL treatment for acute HCV monoinfection. Methods In this investigator-initiated, prospective, multicentre, single-arm study, we recruited 20 adult patients with acute HCV monoinfection from nine centers in Germany. Patients received SOF/VEL (400/100 mg) as a fixed-dose combination tablet once daily for 8 weeks. The primary efficacy endpoint was the proportion of patients with sustained virological response 12 weeks after the end of treatment (SVR12). Results The median HCV RNA viral load at baseline was 104,307 IU/ml; the distribution of HCV genotypes was as follows: GT1a/1b/2/3/4: n = 12/1/1/3/3. Thirteen (65%) of the 20 patients were taking medication for HIV pre-exposure prophylaxis. SVR12 was achieved in all patients who complied with the study protocol (n = 18/18 [100%], per protocol analysis), but the primary endpoint was not met in the intention-to-treat analysis (n = 18/20 [90%]) because two patients were lost to follow-up. One serious adverse event (unrelated to study drug) occurred during 12 weeks of post-treatment follow-up. Conclusions The 8-week treatment with SOF/VEL was well tolerated and highly effective in all adherent patients with acute HCV monoinfection. Early treatment of hepatitis C might effectively prevent the spread of HCV in high-risk groups. Clinical Trial Number NCT03818308. Impact and implications The HepNet acute HCV-V study (NCT03818308), an investigator-initiated, single-arm, multicenter pilot study, demonstrates the efficacy and safety of 8 weeks of daily treatment with the fixed-dose combination sofosbuvir/velpatasvir (400/100 mg) in patients with acute hepatitis C virus (HCV) infection. All patients who completed therapy and were followed-up achieved sustained virologic response. Thus, early treatment with SOF/VEL which might effectively prevent the spread of HCV in high-risk groups can be recommended for patients with acute HCV monoinfection.
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Affiliation(s)
- Benjamin Maasoumy
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany
- German Center for Infection Research (DZIF), HepNet Study-House, Hannover, Germany
- German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany
| | - Patrick Ingiliz
- Zentrum für Infektiologie Berlin-Prenzlauer Berg, Berlin, Germany
- University Hospital Henri-Mondor, INSERM U955, Créteil, France
| | - Christoph D. Spinner
- Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Department of Internal Medicine II, Munich, Germany
| | | | | | - Julian Schulze zur Wiesch
- Medical Department, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany
| | | | - Katja Deterding
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany
- Department of Gastroenterology and Hepatology, University Hospital Essen, 45147 Essen, Germany
| | - Tobias Müller
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
| | - Julia Kahlhöfer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany
- German Center for Infection Research (DZIF), HepNet Study-House, Hannover, Germany
| | - Petra Dörge
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany
- German Center for Infection Research (DZIF), HepNet Study-House, Hannover, Germany
| | | | - Michael P. Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany
| | - Markus Cornberg
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany
- German Center for Infection Research (DZIF), HepNet Study-House, Hannover, Germany
- German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany
- Center for Individualized Infection Medicine (CiiM), Hannover, Germany
| | - for the HepNet Acute HCV-V Study Group
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany
- German Center for Infection Research (DZIF), HepNet Study-House, Hannover, Germany
- German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany
- Zentrum für Infektiologie Berlin-Prenzlauer Berg, Berlin, Germany
- University Hospital Henri-Mondor, INSERM U955, Créteil, France
- Technical University of Munich, School of Medicine, University Hospital Rechts der Isar, Department of Internal Medicine II, Munich, Germany
- Praxis Dr. Cordes, Berlin, Germany
- ICH Study Center Hamburg, Hamburg, Germany
- Medical Department, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany
- Praxis Hohenstaufenring, Köln, Germany
- Department of Gastroenterology and Hepatology, University Hospital Essen, 45147 Essen, Germany
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
- Institute for Biometry, Hannover Medical School, Germany
- Center for Individualized Infection Medicine (CiiM), Hannover, Germany
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15
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Pilewski KA, Wall S, Richardson SI, Manamela NP, Clark K, Hermanus T, Binshtein E, Venkat R, Sautto GA, Kramer KJ, Shiakolas AR, Setliff I, Salas J, Mapengo RE, Suryadevara N, Brannon JR, Beebout CJ, Parks R, Raju N, Frumento N, Walker LM, Fechter EF, Qin JS, Murji AA, Janowska K, Thakur B, Lindenberger J, May AJ, Huang X, Sammour S, Acharya P, Carnahan RH, Ross TM, Haynes BF, Hadjifrangiskou M, Crowe JE, Bailey JR, Kalams S, Morris L, Georgiev IS. Functional HIV-1/HCV cross-reactive antibodies isolated from a chronically co-infected donor. Cell Rep 2023; 42:112044. [PMID: 36708513 PMCID: PMC10372200 DOI: 10.1016/j.celrep.2023.112044] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 09/30/2022] [Accepted: 01/13/2023] [Indexed: 01/28/2023] Open
Abstract
Despite prolific efforts to characterize the antibody response to human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) mono-infections, the response to chronic co-infection with these two ever-evolving viruses is poorly understood. Here, we investigate the antibody repertoire of a chronically HIV-1/HCV co-infected individual using linking B cell receptor to antigen specificity through sequencing (LIBRA-seq). We identify five HIV-1/HCV cross-reactive antibodies demonstrating binding and functional cross-reactivity between HIV-1 and HCV envelope glycoproteins. All five antibodies show exceptional HCV neutralization breadth and effector functions against both HIV-1 and HCV. One antibody, mAb688, also cross-reacts with influenza and coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We examine the development of these antibodies using next-generation sequencing analysis and lineage tracing and find that somatic hypermutation established and enhanced this reactivity. These antibodies provide a potential future direction for therapeutic and vaccine development against current and emerging infectious diseases. More broadly, chronic co-infection represents a complex immunological challenge that can provide insights into the fundamental rules that underly antibody-antigen specificity.
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Affiliation(s)
- Kelsey A Pilewski
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Steven Wall
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Simone I Richardson
- National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa
| | - Nelia P Manamela
- National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa
| | - Kaitlyn Clark
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Tandile Hermanus
- National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa
| | - Elad Binshtein
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Rohit Venkat
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Giuseppe A Sautto
- Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA
| | - Kevin J Kramer
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Andrea R Shiakolas
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Ian Setliff
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Jordan Salas
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Rutendo E Mapengo
- National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa
| | - Naveen Suryadevara
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - John R Brannon
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Connor J Beebout
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Rob Parks
- Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA
| | - Nagarajan Raju
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Nicole Frumento
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Lauren M Walker
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | | | - Juliana S Qin
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Amyn A Murji
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | | | - Bhishem Thakur
- Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA
| | | | - Aaron J May
- Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA
| | - Xiao Huang
- Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA
| | - Salam Sammour
- Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA
| | - Priyamvada Acharya
- Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA; Department of Biochemistry, Duke University, Durham, NC 27710, USA; Department of Surgery, Duke University, Durham, NC 27710, USA
| | - Robert H Carnahan
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Ted M Ross
- Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA; Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA
| | - Barton F Haynes
- Departments of Medicine and Immunology, Duke University, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA
| | - Maria Hadjifrangiskou
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - James E Crowe
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Justin R Bailey
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Spyros Kalams
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Lynn Morris
- National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa
| | - Ivelin S Georgiev
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Computer Science, Vanderbilt University, Nashville, TN 37232, USA; Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA; Program in Computational Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
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16
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Huang MH, Chen GJ, Sun HY, Chen YT, Su LH, Ho SY, Chang SY, Huang SH, Huang YC, Liu WD, Lin KY, Huang YS, Su YC, Liu WC, Hung CC. Risky sexual practices and hepatitis C viremia among HIV-positive men who have sex with men in Taiwan. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2023:S1684-1182(23)00006-3. [PMID: 36702644 DOI: 10.1016/j.jmii.2023.01.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 12/23/2022] [Accepted: 01/09/2023] [Indexed: 01/19/2023]
Abstract
BACKGROUND Understanding the risk behaviors associated with sexually-transmitted hepatitis C virus (HCV) infection among men who have sex with men (MSM) may inform the public health policies and interventions aiming to achieve HCV microelimination. METHODS HIV-positive MSM who had one of the following conditions were enrolled to undergo face-to-face questionnaire interviews to collect information on their sexual practices in the past 12 months: (1) elevation of aminotransferases in the past 6 months; (2) acquisition of sexually transmitted infections in the past 6 months; and (3) previous HCV infections. Plasma HCV RNA were tested at enrolment and every 3 months during follow-up. Baseline characteristics and risky behaviors were compared to identify factors associated with HCV viremia between HCV-viremic MSM and HCV-aviremic MSM in multivariate analysis. RESULTS Among 781 MSM with a median age of 36 years, 57 (7.3%) had HCV viremia and 724 (92.7%) no HCV viremia during follow-up. A high proportion (38.9%) of the participants reported having used recreational drugs in the past 12 months, with 34.4% of them having slamming, but only 4.8% reported having shared their injection equipment. In multivariate analysis, use of recreational drugs (adjusted odds ratio [aOR], 2.14; 95% CI, 1.16-3.96), having participated in group sex (aOR, 2.35; 95% CI 1.24-4.40) and having had condomless receptive anal intercourse (aOR, 1.97; 95% CI 1.07-3.62) were significantly associated with HCV viremia. CONCLUSION Among high-risk HIV-positive MSM, use of recreational drugs and risky sexual contacts were associated with HCV viremia, suggesting the mucosal contacts as the major route of HCV transmission.
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Affiliation(s)
- Miao-Hui Huang
- Department of Internal Medicine, Hualien Tzu Chi Hospital and Tzu Chi University, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Guan-Jhou Chen
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College Medicine, Taipei, Taiwan; Min-Sheng General Hospital, Taoyuan, Taiwan
| | - Hsin-Yun Sun
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College Medicine, Taipei, Taiwan
| | - Yi-Ting Chen
- Center of Infection Control, National Taiwan University Hospital, Taipei, Taiwan
| | - Li-Hsin Su
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College Medicine, Taipei, Taiwan
| | - Shu-Yuan Ho
- Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College Medicine, Taipei, Taiwan
| | - Sui-Yuan Chang
- Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College Medicine, Taipei, Taiwan; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Sung-Hsi Huang
- Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan; Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Chia Huang
- Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Wang-Da Liu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College Medicine, Taipei, Taiwan; Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Kuan-Yin Lin
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College Medicine, Taipei, Taiwan; Center of Infection Control, National Taiwan University Hospital, Taipei, Taiwan
| | - Yu-Shan Huang
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College Medicine, Taipei, Taiwan
| | - Yi-Ching Su
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College Medicine, Taipei, Taiwan
| | - Wen-Chun Liu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College Medicine, Taipei, Taiwan
| | - Chien-Ching Hung
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College Medicine, Taipei, Taiwan; Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; China Medical University, Taichung, Taiwan.
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17
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Chen GJ, Ho SY, Su LH, Chang SY, Hsieh SM, Sheng WH, Liu WD, Huang YS, Lin KY, Chen YT, Su YC, Liu WC, Sun HY, Hung CC. Hepatitis C microelimination among people living with HIV in Taiwan. Emerg Microbes Infect 2022; 11:1664-1671. [PMID: 35608049 PMCID: PMC9225706 DOI: 10.1080/22221751.2022.2081620] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
To reach the WHO target of hepatitis C virus (HCV) elimination by 2025, Taiwan started to implement free-of-charge direct-acting antiviral (DAA) treatment programme in 2017. Evaluating the progress of HCV microelimination among people living with HIV (PLWH) is a critical step to identify the barriers to HCV elimination. PLWH seeking care at a major hospital designated for HIV care in Taiwan between January 2011 and December 2021 were retrospectively included. For PLWH with HCV-seropositive or HCV seroconversion during the study period, serial HCV RNA testing was performed using archived samples to confirm the presence of HCV viremia and estimate the prevalence and incidence of HCV viremia. Overall, 4199 PLWH contributed to a total of 27,258.75 person-years of follow-up (PYFU). With the reimbursement of DAAs and improvement of access to treatments, the prevalence of HCV viremia has declined from its peak of 6.21% (95% CI, 5.39–7.12%) in 2018 to 2.09% (95% CI, 1.60–2.77%) in 2021 (decline by 66.4% [95% CI, 55.4–74.7%]); the incidence has declined from 25.94 per 1000 PYFU (95% CI, 20.44–32.47) in 2019 to 12.15% per 1000 PYFU (95% CI, 8.14–17.44) (decline by 53.2% [95% CI, 27.3–70.6%]). However, the proportion of HCV reinfections continued to increase and accounted for 82.8% of incident HCV infections in 2021. We observed significant declines of HCV viremia among PLWH with the expansion of the DAA treatment programme in Taiwan. Further improvement of the access to DAA retreatments is warranted to achieve the goal of HCV microelimination.
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Affiliation(s)
- Guan-Jhou Chen
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.,Min-Sheng General Hospital, Taoyuan, Taiwan
| | - Shu-Yuan Ho
- Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Li-Hsin Su
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Sui-Yuan Chang
- Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Szu-Min Hsieh
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wang-Huei Sheng
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wang-Da Liu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Yu-Shan Huang
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Kuan-Yin Lin
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Ting Chen
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Ching Su
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wen-Chun Liu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Hsin-Yun Sun
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chien-Ching Hung
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan
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18
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Chen GJ, Sun HY, Chang SY, Su LH, Chen YT, Hsieh SM, Liu WD, Sheng WH, Huang YS, Lin KY, Su YC, Liu WC, Hung CC. Sexually-transmitted hepatitis C virus reinfections among people living with HIV in Taiwan: the emerging role of genotype 6. Emerg Microbes Infect 2022; 11:1227-1235. [PMID: 35412439 PMCID: PMC9067974 DOI: 10.1080/22221751.2022.2065933] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Hepatitis C virus (HCV) reinfections after successful treatment with direct-acting antivirals (DAAs) pose a significant challenge to HCV elimination, especially among high-risk people living with HIV (PLWH). In this study, PLWH who had achieved HCV viral clearance with DAAs were included between January 2018 and June 2021. PLWH having acquired HCV infections after 2017 were classified as "recent-infection group," and those before 2017 as "remote-infection group," and the incidences of HCV reinfection were compared between two groups. Clinical and behavioural characteristics were evaluated to identify associated factors with HCV reinfection. A total of 284 PLWH were included: 179 in the recent-infection group and 105 in the remote-infection group. After a median follow-up of 2.32 years (interquartile range [IQR], 0.13-3.94), the overall incidence of HCV reinfection was 5.8 per 100 person-years of follow-up (PYFU). The incidence in the recent-infection group was significantly higher than that in the remote-infection group (9.8 vs. 0.4 per 100 PYFU, p < 0.001). The leading HCV genotypes before DAA treatment were genotypes 2 (31.0%), 1b (26.8%), and 6 (21.8%); however, genotype 6 (58.8%) became predominant upon reinfection. Younger age (adjusted odds ratio [aOR] per 1-year increase, 0.95; 95% CI, 0.90-0.99), condomless receptive anal sex (aOR, 14.5; 95% CI, 2.37-88.8), rimming (aOR, 3.87; 95% CI, 1.14-13.1), and recent syphilis (aOR, 2.73; 95% CI, 1.26-5.91) were linked to HCV reinfections. In conclusion, PLWH acquiring HCV after 2017 had a significantly higher risk for sexually-transmitted HCV reinfections. The predominance of HCV genotype 6 reinfections suggests possible on-going clustered HCV infections among at-risk PLWH.
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Affiliation(s)
- Guan-Jhou Chen
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.,Min-Sheng General Hospital, Taoyuan, Taiwan
| | - Hsin-Yun Sun
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Sui-Yuan Chang
- Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Li-Hsin Su
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Ting Chen
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Szu-Min Hsieh
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wan-Da Liu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wang-Huei Sheng
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yu-Shan Huang
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Kuan-Yin Lin
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Ching Su
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wen-Chun Liu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chien-Ching Hung
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.,China Medical University, Taichung, Taiwan
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19
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Burgui C, San Miguel R, Goñi-Esarte S, Juanbeltz R, Úriz-Otano JI, Reparaz J, Sarobe M, Zozaya JM, Castilla J. Effectiveness of hepatitis C antiviral treatment and feasibility of hepatitis C elimination goal. Postgrad Med 2022; 135:352-360. [PMID: 36305320 DOI: 10.1080/00325481.2022.2141499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
OBJECTIVES Second-generation direct-acting antivirals (DAAs) have shown high efficacy in the treatment of chronic hepatitis C virus (HCV) infections in clinical trials. This study aimed to estimate the effectiveness in real-life conditions and their capacity to eliminate HCV infection in the general population. METHODS In this observational cohort study, patients with active HCV infection who commenced DAA treatment between 2015 and 2020 in Navarre, Spain, were studied. Sustained virological response (SVR), defined as an undetectable viral load 12 weeks after the end of treatment, was evaluated until the end of 2021. RESULTS Of a total 1366 HCV-infected patients that commenced treatment, 19.3% (n = 263) were HIV-coinfected. After the first DAA treatment, SVR was achieved in 96.6% (n = 1320/1366) of patients and in 97.7% (95% confidence interval [CI] 96.6%-98.3%) of those who completed treatment (per-protocol analysis; n = 1320/1351). SVR was achieved in 97.9% (n = 1066/1089) and 96.9% (n = 254/262) of mono-infected and HIV-coinfected patients, respectively. Thirty-one patients had virological failure due to non-response (n = 19), poor compliance (n = 9), and with adverse events (n = 3). Of 27 patients that received a second treatment, 24 attained SVR (one after a third treatment), two died, and one that did not achieve SVR declined a third treatment. Three patients were re-infected, re-treated, and achieved SVR. At the end of the study, 1344 patients (98.4%, 95% CI 97.6%-98.9%) had achieved SVR, and only 1.8% needed more than one course of treatment. All patients who completed the treatment and were followed-up achieved SVR. CONCLUSION With DAAs, SVR was achieved in all patients with active HCV infection who completed follow-up, and a second course of treatment was only necessary in a small proportion of patients. Adherence to treatment is essential for HCV infection elimination.
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Affiliation(s)
- Cristina Burgui
- Instituto de Salud Pública de Navarra, Pamplona, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Spain
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Ramón San Miguel
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Servicio de Farmacia Hospitalaria, Hospital Universitario de Navarra, Pamplona, Spain
| | - Silvia Goñi-Esarte
- Servicio de Digestivo, Hospital Universitario de Navarra, Pamplona, Spain
| | - Regina Juanbeltz
- CIBER Epidemiología y Salud Pública (CIBERESP), Spain
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Servicio de Farmacia Hospitalaria, Hospital Universitario de Navarra, Pamplona, Spain
| | - Juan Isidro Úriz-Otano
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Servicio de Digestivo, Hospital Universitario de Navarra, Pamplona, Spain
| | - Jesús Reparaz
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Servicio de Medicina Interna, Hospital Universitario de Navarra, Pamplona, Spain
| | - Maite Sarobe
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Servicio de Farmacia Hospitalaria, Hospital Universitario de Navarra, Pamplona, Spain
| | - José Manuel Zozaya
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
- Servicio de Digestivo, Hospital Universitario de Navarra, Pamplona, Spain
| | - Jesús Castilla
- Instituto de Salud Pública de Navarra, Pamplona, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Spain
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
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20
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Abiodun OE, Adebimpe O, Ndako JA, Oludoun O, Aladeitan B, Adeniyi M. Mathematical modeling of HIV-HCV co-infection model: Impact of parameters on reproduction number. F1000Res 2022; 11:1153. [PMID: 36636470 PMCID: PMC9817180 DOI: 10.12688/f1000research.124555.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/08/2022] [Indexed: 09/19/2023] Open
Abstract
Background: Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) are both as classified blood-borne viruses since they are transmitted through contact with contaminated blood. Approximately 1.3 million of the 2.75 million global HIV/HCV carriers inject drugs (PWID). HIV co-infection has a harmful effect on the progression of HCV, resulting in greater rates of HCV persistence after acute infection, higher viral levels, and accelerated progression of liver fibrosis and end-stage liver disease. In this study, we developed and investigated a mathematical model for the dynamical behavior of HIV/AIDS and HCV co-infection, which includes therapy for both diseases, vertical transmission in HIV cases, unawareness and awareness of HIV infection, inefficient HIV treatment follow-up, and efficient condom use. Methods: Positivity and boundedness of the model under investigation were established using well-known theorems. The equilibria were demonstrated by bringing all differential equations to zero. The associative reproduction numbers for mono-infected and dual-infected models were calculated using the next-generation matrix approach. The local and global stabilities of the models were validated using the linearization and comparison theorem and the negative criterion techniques of bendixson and dulac, respectively. Results: The growing prevalence of HIV treatment dropout in each compartment of the HIV model led to a reduction in HIV on treatment compartments while other compartments exhibited an increase in populations . In dually infected patients, treating HCV first reduces co-infection reproduction number R ech , which reduces liver cancer risk. Conclusions: From the model's results, we infer various steps that policymakers could take to reduce the number of mono-infected and co-infected individuals.
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Affiliation(s)
| | - Olukayode Adebimpe
- Mathematics and Statistics, First Technical University, Ibadan, Oyo, Nigeria
| | - James A. Ndako
- Physical Sciences, Landmark University, Omu Aran, State, 251101, Nigeria
| | - Olajumoke Oludoun
- Physical Sciences, Landmark University, Omu Aran, State, 251101, Nigeria
| | | | - Michael Adeniyi
- Mathematics and Statistics, Lagos State Polytechnic, Lagos, Lagos, Nigeria
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21
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Abiodun OE, Adebimpe O, Ndako JA, Oludoun O, Aladeitan B, Adeniyi M. Mathematical modeling of HIV-HCV co-infection model: Impact of parameters on reproduction number. F1000Res 2022; 11:1153. [PMID: 36636470 PMCID: PMC9817180 DOI: 10.12688/f1000research.124555.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/30/2022] [Indexed: 12/23/2022] Open
Abstract
Background: Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) are both classified as blood-borne viruses since they are transmitted through contact with contaminated blood. Approximately 1.3 million of the 2.75 million global HIV/HCV carriers are people who inject drugs (PWID). HIV co-infection has a harmful effect on the progression of HCV, resulting in greater rates of HCV persistence after acute infection, higher viral levels, and accelerated progression of liver fibrosis and end-stage liver disease. In this study, we developed and investigated a mathematical model for the dynamical behavior of HIV/AIDS and HCV co-infection, which includes therapy for both diseases, vertical transmission in HIV cases, unawareness and awareness of HIV infection, inefficient HIV treatment follow-up, and efficient condom use. Methods: Positivity and boundedness of the model under investigation were established using well-known theorems. The equilibria were demonstrated by bringing all differential equations to zero. The associative reproduction numbers for mono-infected and dual-infected models were calculated using the next-generation matrix approach. The local and global stabilities of the models were validated using the linearization and comparison theorem and the negative criterion techniques of bendixson and dulac, respectively. Results: The growing prevalence of HIV treatment dropout in each compartment of the HIV model led to a reduction in HIV on treatment compartments while other compartments exhibited an increase in populations . In dually infected patients, treating HCV first reduces co-infection reproduction number R ech , which reduces liver cancer risk. Conclusions: From the model's results, we infer various steps (such as: campaigns to warn individuals about the consequences of having multiple sexual partners; distributing more condoms to individuals; continuing treatment for chronic HCV and AIDS) that policymakers could take to reduce the number of mono-infected and co-infected individuals.
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Affiliation(s)
| | - Olukayode Adebimpe
- Mathematics and Statistics, First Technical University, Ibadan, Oyo, Nigeria
| | - James A. Ndako
- Physical Sciences, Landmark University, Omu Aran, State, 251101, Nigeria
| | - Olajumoke Oludoun
- Physical Sciences, Landmark University, Omu Aran, State, 251101, Nigeria
| | | | - Michael Adeniyi
- Mathematics and Statistics, Lagos State Polytechnic, Lagos, Lagos, Nigeria
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22
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Persistent Transmission of HCV among Men Who Have Sex with Men despite Widespread Screening and Treatment with Direct-Acting Antivirals. Viruses 2022; 14:v14091953. [PMID: 36146760 PMCID: PMC9502248 DOI: 10.3390/v14091953] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 08/25/2022] [Accepted: 08/27/2022] [Indexed: 11/21/2022] Open
Abstract
Background: In the Netherlands, unrestricted access to direct-acting antivirals (DAAs) halved the incidence of acute hepatitis C virus (HCV) infections among HIV-infected men who have sex with men (MSM). To develop strategies that can further reduce the spread of HCV, it is important to understand the transmission dynamics of HCV. We used phylogenetic analysis of a dense sample of MSM to provide insight into the impact of unrestricted access to DAAs on HCV transmission in the Netherlands and in Belgium. Methods: We included 89 MSM that were recently infected with HCV genotype 1a in ten Dutch and one Belgian HIV treatment centers. Sequences were generated using next gene sequencing and Sanger sequencing. Maximum likelihood phylogenetic analysis (general time reversible model) was performed on concatenated NS5A and NS5B sequences and a reference set of 389 highly similar control sequences selected from GenBank. A cluster was based on a minimum bootstrap support of 90% and a 3% genetic distance threshold. Results: We found that 78 (88%) of individuals were part of seven major clusters. All clusters included individuals from across the study region, however, different cities were part of different clusters. In three clusters, HIV-negative MSM clustered with sequences from HIV-positive MSM. All clusters that were observed before the introduction of DAAs persisted after unrestricted access to DAAs became available. Conclusion: Recently acquired HCV infections among MSM in the Netherlands and Belgium are strongly clustered and therefore highly suitable for targeted prevention strategies, such as contact tracing and partner notification. Importantly, despite an HCV incidence reduction after high DAA uptake and continuously monitoring, HCV transmission persisted in the same clusters.
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23
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Wan Z, Sun P, Dzakah EE, Huang L, Shuai P, Liu Y. Reinfection rate of hepatitis C in HIV-1 positive men who have sex with men: A systematic review and meta-analysis. Front Public Health 2022; 10:855989. [PMID: 35968434 PMCID: PMC9372531 DOI: 10.3389/fpubh.2022.855989] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 07/07/2022] [Indexed: 12/02/2022] Open
Abstract
Purpose A reduction of 80% in new Hepatitis C virus (HCV) infection is expected by 2030. However, high HCV reinfection rates have been reported among the high-risk population. This meta-analysis aimed to assess the HCV reinfection rate after successful treatment of HIV-1 coinfected MSM populations. Methods Bibliographic databases were searched and a random-effect model was utilized to calculate the pooled HCV reinfection rate. Sub-group and meta-regression were used to explore heterogeneity among selected studies. A funnel plot and Egger's regression test were performed to estimate the publication bias. Results Sixteen studies with 9,017.2 person-years (PY) follow-up were included. The overall HCV reinfection rate following successful treatment among HIV-1-infected MSM was 5.27/100 PY (95% CI, 3.98, 6.96). Lower reinfection rates were observed in developed parts of Europe (5.28/100 PY; 95% CI, 3.73, 6.84) and North America (3.92/100 PY; 95% CI, 1.67, 6.17). Reinfection rates among people with HCV test intervals of fewer than 6 months (7.59/100 PY; 95% CI: 5.15, 10.03) were significantly higher than those with more than 6 months test interval (2.88/100 PY; 95% CI: 2.26, 3.50), with an adjusted RR of 1.86 (95% CI, 1.06, 3.13). The adjusted study factors explained 91.03% the of studies' heterogeneity. Conclusion HCV reinfection rate was high in successfully treated MSM who were coinfected with HIV-1. A shorter HCV test interval may help to explore more HCV reinfections. HCV reinfection rate studies from HIV-1 coinfected MSM in underdeveloped countries are urgently needed. Meta registration PROSPERO: CRD42021285206, URL: https://www.crd.york.ac.uk/prospero/.
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Affiliation(s)
- Zhengwei Wan
- Department of Health Management Center and Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Ping Sun
- Department of Health Management Center and Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Emmanuel Enoch Dzakah
- Department of Molecular Biology and Biotechnology, School of Biological Sciences, College of Agriculture and Natural Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Liping Huang
- Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Ping Shuai
- Department of Health Management Center and Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
- *Correspondence: Ping Shuai
| | - Yuping Liu
- Department of Health Management Center and Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
- Yuping Liu
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24
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Sun HY, Chiang C, Huang SH, Guo WJ, Chuang YC, Huang YC, Yang CJ, Su LH, Chen YT, Chen YW, Hsu FC, Ho SY, Liu WC, Su YC, Chang SY, Hsiao CF, Hung CC, Yu ML. Three-Stage Pooled Plasma Hepatitis C Virus RNA Testing for the Identification of Acute HCV Infections in At-Risk Populations. Microbiol Spectr 2022; 10:e0243721. [PMID: 35499354 PMCID: PMC9241589 DOI: 10.1128/spectrum.02437-21] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 04/11/2022] [Indexed: 01/26/2023] Open
Abstract
Timely diagnosis and treatment of hepatitis C virus (HCV) infection may prevent its transmission. We evaluated the performance and cost reductions of the pooled plasma HCV RNA testing strategy to identify acute HCV infections among people living with HIV (PLWH). PLWH with sexually transmitted infections, elevated aminotransferases within the past 6 months or past HCV infections (high-risk) and those without (low-risk) were enrolled prospectively. Participants underwent three-stage pooled plasma HCV RNA testing every 12 to 24 weeks until detection of HCV RNA or completion of a 48-week follow-up. The three-stage strategy combined 20 individual specimens into a stage 1 pool, 5 individual specimens from the stage 1 pool that tested positive for HCV RNA in the stage 2 mini-pool, followed by testing of individual specimens of the stage 2 mini-pool tested positive for HCV RNA. A simulation was constructed to investigate the cost reductions and pooled sensitivity and specificity under different combinations of HCV prevalence and pool/mini-pool sizes. Between June 25, 2019 and March 31, 2021, 32 cases of incident HCV viremia were identified in 760 high-risk PLWH that were enrolled 834 times, giving an incidence rate of 56.6 per 1000 person-years of follow-up (PYFU). No cases of HCV viremia were identified in 557 low-risk PLWH during a total of 269.2 PYFU. Simulation analysis suggested that this strategy could reduce HCV RNA testing cost by 50% to 86% with HCV viremia prevalence of 1% to 5% and various pooled sizes despite compromised pooled sensitivity. This pooled plasma HCV RNA testing strategy is cost-saving to identify acute HCV infections in high-risk populations with HCV viremia prevalence of 1% to 5%. IMPORTANCE Our three-stage pooled plasma HCV RNA testing successfully identified HCV viremia in high-risk PLWH with a testing cost reduction of 84.5%. Simulation analysis offered detailed information regarding the selection of pool and mini-pool sizes in settings of different HCV epidemiology and the performance of HCV RNA testing to optimize the cost reduction.
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Affiliation(s)
- Hsin-Yun Sun
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chieh Chiang
- Department of Mathematics, Tamkang University, New Taipei City, Taiwan
| | - Sung-Hsi Huang
- Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan
- Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wen-Jin Guo
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
| | - Yu-Chung Chuang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Chia Huang
- Department of Internal Medicine, National Taiwan University Hospital Biomedical Park Branch, Hsin-Chu, Taiwan
| | - Chia-Jui Yang
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Li-Hsin Su
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Ting Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yea-Wen Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Fu-Chiang Hsu
- Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Laboratory Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shu-Yuan Ho
- Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Laboratory Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Wen-Chun Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Ching Su
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Sui-Yuan Chang
- Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Laboratory Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chin-Fu Hsiao
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
| | - Chien-Ching Hung
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
- China Medical University, Taichung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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25
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Sepúlveda-Crespo D, Yélamos MB, Díez C, Gómez J, Hontañón V, Torresano-Felipe F, Berenguer J, González-García J, Ibañez-Samaniego L, Llop E, Olveira A, Martínez J, Resino S, Martínez I. Negative impact of HIV infection on broad-spectrum anti-HCV neutralizing antibody titers in HCV-infected patients with advanced HCV-related cirrhosis. Biomed Pharmacother 2022; 150:113024. [PMID: 35483197 DOI: 10.1016/j.biopha.2022.113024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/20/2022] [Accepted: 04/20/2022] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVES The current study aimed to assess the impact of HIV on the production of anti-HCV antibodies in HCV-infected individuals with advanced HCV-related cirrhosis before and 36 weeks after the sustained virological response (SVR) induced by direct-acting antivirals (DAAs) therapy. METHODS Prospective study on 62 patients (50 HIV/HCV-coinfected and 12 HCV-monoinfected). Plasma anti-E2 and HCV-nAbs were determined respectively by ELISA and microneutralization assays. RESULTS At baseline, the HCV-group had higher anti-E2 levels against Gt1a (p = 0.012), Gt1b (p = 0.023), and Gt4a (p = 0.005) than the HIV/HCV-group. After SVR, anti-E2 titers against Gt1a (p < 0.001), Gt1b (p = 0.001), and Gt4a (p = 0.042) were also higher in the HCV-group than HIV/HCV-group. At 36 weeks post-SVR, plasma anti-E2 titers decreased between 1.3 and 1.9-fold in the HIV/HCV-group (p < 0.001) and between 1.5 and 1.8-fold in the HCV-group (p ≤ 0.001). At baseline, the HCV-group had higher titers of HCV-nAbs against Gt1a (p = 0.022), Gt1b (p = 0.002), Gt2a (p < 0.001), and Gt4a (p < 0.001) than the HIV/HCV-group. After SVR, HCV-nAbs titers against Gt1a (p = 0.014), Gt1b (p < 0.001), Gt2a (p = 0.002), and Gt4a (p = 0.004) were also higher in the HCV-group. At 36 weeks post-SVR, HCV-nAbs decreased between 2.6 and 4.1-fold in the HIV/HCV-group (p < 0.001) and between 1.9 and 4.0-fold in the HCV-group (p ≤ 0.001). CONCLUSIONS HIV/HCV-coinfected patients produced lower levels of broad-spectrum anti-HCV antibodies than HCV-monoinfected patients.
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Affiliation(s)
- Daniel Sepúlveda-Crespo
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - María Belén Yélamos
- Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad Complutense, Madrid, Spain
| | - Cristina Díez
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain; Unidad de Enfermedades Infecciosas/VIH; Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain
| | - Julián Gómez
- Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad Complutense, Madrid, Spain
| | - Víctor Hontañón
- Unidad de VIH; Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid, Spain; Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain
| | - Francisco Torresano-Felipe
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Juan Berenguer
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain; Unidad de Enfermedades Infecciosas/VIH; Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain
| | - Juan González-García
- Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain; Unidad de VIH; Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid, Spain; Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain
| | - Luis Ibañez-Samaniego
- Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain; Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Elva Llop
- Servicio de Aparato Digestivo, Hospital Universitario Puerta de Hierro, Madrid, Spain
| | - Antonio Olveira
- Instituto de Investigación Hospital Universitario La Paz, Madrid, Spain; Servicio de Aparato Digestivo, Hospital Universitario La Paz, Madrid, Spain
| | - Javier Martínez
- Servicio de Aparato Digestivo, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
| | - Isidoro Martínez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
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26
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Hosseini-Hooshyar S, Hajarizadeh B, Bajis S, Law M, Janjua NZ, Fierer DS, Chromy D, Rockstroh JK, Martin TCS, Ingiliz P, Hung CC, Dore GJ, Martinello M, Matthews GV. Risk of hepatitis C reinfection following successful therapy among people living with HIV: a global systematic review, meta-analysis, and meta-regression. THE LANCET HIV 2022; 9:e414-e427. [DOI: 10.1016/s2352-3018(22)00077-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 02/21/2022] [Accepted: 03/14/2022] [Indexed: 12/17/2022]
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27
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Marquez LK, Ingiliz P, Boesecke C, Krznaric I, Schewe K, Lutz T, Mauss S, Christensen S, Rockstroh JK, Jain S, He F, Wertheim JO, Martin NK. Establishing a framework towards monitoring HCV microelimination among men who have sex with men living with HIV in Germany: A modeling analysis. PLoS One 2022; 17:e0267853. [PMID: 35551326 PMCID: PMC9098082 DOI: 10.1371/journal.pone.0267853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 04/16/2022] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Prior to direct-acting antivirals (DAAs), HCV incidence rose among men who have sex with men (MSM) living with HIV infection in Germany despite high hepatitis C virus (HCV) treatment rates. We establish a HCV elimination modeling framework to evaluate whether existing treatment rates can achieve the World Health Organization (WHO) incidence target among MSM living with HIV in Germany. METHODS To evaluate progress towards HCV elimination in Germany, we adapted a previously published HCV transmission model among MSM living with diagnosed HIV. We modelled HCV incidence and prevalence until 2030 (relative to 2015) under existing treatment and DAA scale-up and explored potential impacts of disruptions in treatment and behavioral risk reduction due to the COVID-19 pandemic. RESULTS Continuing current treatment rates will result in stable HCV incidence among MSM living with HIV in Germany between 2015-2030. The WHO HCV incidence target is achievable under DAA scale-up to 100% treatment combined with treatment of those previously diagnosed and untreated (at a rate of 15%/year) and would result in greater reductions with early treatment (3 vs 6 months) reducing incidence from 4.0/100person-years to 0.8/100person-years by 2030. A 12-month disruption to HCV treatment (20% reduction) and risk behaviors (25%,50%,75% reduction) during the COVID-19 pandemic would result in a 15% relative increase in total HCV incidence in 2030 compared to that expected under the status quo. CONCLUSIONS HCV elimination among MSM living with HIV in Germany requires further DAA scale-up among those newly diagnosed combined with efforts to treat those previously diagnosed but untreated. Prospective monitoring will establish whether Germany is on track for HCV microelimination.
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Affiliation(s)
- Lara K Marquez
- Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA, United States of America
| | - Patrick Ingiliz
- Center for Infectiology, Berlin, Germany
- Hepatology Department, Henri-Mondor Hospital, INSERM U955, Créteil, France
| | | | | | | | | | - Stefan Mauss
- Center for HIV and Hepatogastroenterology, Duesseldorf, Germany
| | - Stefan Christensen
- CIM Münster, Münster, Germany
- Department of Gastroenterology and Hepatology, Muenster University Hospital, Muenster, Germany
| | | | - Sonia Jain
- Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, United States of America
| | - Feng He
- Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, United States of America
| | - Joel O Wertheim
- Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA, United States of America
| | - Natasha K Martin
- Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA, United States of America
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28
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O'Shea J, Oliver N, Cartwright EJ. Diagnosis and Clinical Manifestations of Acute Hepatitis C Infection in People Living with HIV. AIDS Patient Care STDS 2022; 36:172-177. [PMID: 35507325 DOI: 10.1089/apc.2022.0021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
HIV/hepatitis C virus (HCV) coinfection is a global health problem with overlapping modes of transmission. We performed a single-center retrospective case series of acute HCV infections at the Atlanta Veterans Affairs Health Care System between January 2001 and June 2020 to better characterize the presentation and clinical course of acute HCV among veterans with HIV. Cases were discovered through routine clinical care. We identified 29 cases of acute HCV: all men. Risk for HCV acquisition included men who have sex with men (MSM; 93%) and injection drug use (17%). Thirteen (45%) had a concurrent sexually transmitted infection (STI). Symptoms were seen in 76% of acute HCV cases and resulted in hospitalization in 59% of symptomatic cases. Seven (24%) presented as HCV antibody seronegative. Three never seroconverted, all with CD4 T cell counts <200. Spontaneous HCV clearance occurred in 21% (n = 6) and was more common in those who developed jaundice (p = 0.01). Time to treatment was significantly reduced in the direct-acting antivirals (DAAs) era versus the interferon era (300 vs. 1631 days, p < 0.01). Of those who did not spontaneously clear, 87% were treated (n = 20/23) and 95% (n = 19/20) achieved sustained virological response. Three patients died before HCV treatment, all in the pre-DAA period (one death was liver related). In this case series of acute HCV infection in persons with HIV, many were symptomatic MSM who had a concurrent STI, suggesting sexual HCV transmission. Some presented as HCV antibody negative, highlighting the role of enhanced HCV screening and treatment in MSM with HIV to prevent HCV transmission in sexual networks.
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Affiliation(s)
- Jesse O'Shea
- Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Nora Oliver
- Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA
- Infectious Diseases, Atlanta VA Health Care System, Decatur, Georgia, USA
| | - Emily J. Cartwright
- Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA
- Infectious Diseases, Atlanta VA Health Care System, Decatur, Georgia, USA
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29
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Chromy D, Bauer DJM, Simbrunner B, Jachs M, Hartl L, Schwabl P, Schwarz C, Rieger A, Grabmeier‐Pfistershammer K, Trauner M, Ferenci P, Mandorfer M, Gschwantler M, Reiberger T. The 'Viennese epidemic' of acute HCV in the era of direct-acting antivirals. J Viral Hepat 2022; 29:385-394. [PMID: 35274399 PMCID: PMC9415118 DOI: 10.1111/jvh.13665] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Accepted: 02/15/2022] [Indexed: 01/01/2023]
Abstract
The recently reported epidemic of acute hepatitis C virus (HCV) infections -observed predominantly among men who have sex with men (MSM)-may now decline due to wide availability of direct-acting antivirals (DAAs). This study aimed to investigate the current trends of acute hepatitis C in Vienna. Patients presenting with acute hepatitis C between 01/2007 and12/2020 at the Vienna General Hospital were retrospectively enrolled and followed after virologic clearance/eradication. The introduction of unrestricted DAA access after 09/17 defined the 'DAA era', as compared to the 'pre-DAA era' prior to 09/17. We identified 134 acute hepatitis C cases in 119 patients with a mean age of 39 ± 9 years at inclusion. The majority of patients were male (92%), HIV-positive (88%) and MSM (85%). In the DAA era, a history of prior chronic HCV infection at inclusion was found in 24% (11/46) compared to 7% (5/73) in the pre-DAA era (p = .012). The annual rate of acute hepatitis C cases increased in the DAA era (17.11 per year) compared to the pre-DAA era (7.76 per year). The DAA era included an AHC-genotype-2 cluster and more HIV-negative acute hepatitis C cases (0% (0/73) vs. 30% (14/46), p < .001). Patients were followed after spontaneous clearance or sustained virologic treatment response (SVR) for a total of 251.88 patient-years (median 1.39 years per patient). In the DAA era, we recorded 15 acute hepatitis C-reinfections - corresponding to an incidence rate of 5.96 (95% CI: 3.57-9.66) reinfections per 100-patient-years. We continue to observe a high incidence of acute hepatitis C in Vienna in the DAA era-primarily among HIV-positive MSM, but increasingly also in HIV-negative MSM.
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Affiliation(s)
- David Chromy
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna HIV & Liver Study GroupViennaAustria
- Department of DermatologyMedical University of ViennaViennaAustria
| | - David J. M. Bauer
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna HIV & Liver Study GroupViennaAustria
| | - Benedikt Simbrunner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna HIV & Liver Study GroupViennaAustria
| | - Matthias Jachs
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna HIV & Liver Study GroupViennaAustria
| | - Lukas Hartl
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna HIV & Liver Study GroupViennaAustria
| | - Philipp Schwabl
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna HIV & Liver Study GroupViennaAustria
| | - Caroline Schwarz
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna HIV & Liver Study GroupViennaAustria
- Department of Internal Medicine IVWilhelminenspitalWiener Gesundheitsverbund (WiGeV) der Stadt WienViennaAustria
| | - Armin Rieger
- Vienna HIV & Liver Study GroupViennaAustria
- Department of DermatologyMedical University of ViennaViennaAustria
| | - Katharina Grabmeier‐Pfistershammer
- Vienna HIV & Liver Study GroupViennaAustria
- Center for Pathophysiology, Infectiology and ImmunologyInstitute of ImmunologyMedical University ViennaViennaAustria
| | - Michael Trauner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna HIV & Liver Study GroupViennaAustria
| | - Peter Ferenci
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna HIV & Liver Study GroupViennaAustria
| | - Michael Gschwantler
- Vienna HIV & Liver Study GroupViennaAustria
- Department of Internal Medicine IVWilhelminenspitalWiener Gesundheitsverbund (WiGeV) der Stadt WienViennaAustria
| | - Thomas Reiberger
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
- Vienna HIV & Liver Study GroupViennaAustria
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30
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Di Marco L, La Mantia C, Di Marco V. Hepatitis C: Standard of Treatment and What to Do for Global Elimination. Viruses 2022; 14:505. [PMID: 35336911 PMCID: PMC8954407 DOI: 10.3390/v14030505] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 02/09/2022] [Accepted: 02/21/2022] [Indexed: 12/04/2022] Open
Abstract
Hepatitis C virus infection has a substantial effect on morbidity and mortality worldwide because it is a cause of cirrhosis, hepatocellular carcinoma, liver transplantation, and liver-related death. Direct acting antiviral drugs available today have high efficacy and excellent safety and can be used in all patients with clinically evident chronic liver disease and in groups that demonstrate risk behaviors to reduce the spread of infection. The Global Health Strategy of WHO to eliminate hepatitis infection by 2030 assumes "a 90% reduction in new cases of chronic hepatitis C, a 65% reduction in hepatitis C deaths, and treatment of 80% of eligible people with HCV infections". In this review effective models and strategies for achieving the global elimination of HCV infection are analyzed. The screening strategies must be simple and equally effective in high-risk groups and in the general population; fast and effective models for appropriate diagnosis of liver disease are needed; strategies for direct acting antiviral drug selection must be cost-effective; linkage to care models in populations at risk and in marginalized social classes must be specifically designed and applied; strategies for obtaining an effective vaccine against HCV infection have yet to be developed.
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Affiliation(s)
- Lorenza Di Marco
- Gastroenterology Unit, Department of Medical Specialties, University of Modena & Reggio Emilia, 41100 Modena, Italy;
- Clinical and Experimental Medicine PhD Program, University of Modena & Reggio Emilia, 41100 Modena, Italy
| | - Claudia La Mantia
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy;
| | - Vito Di Marco
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy;
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31
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Cheng CY, Ku SY, Lin YC, Chen CP, Cheng SH, Lin IF. Incidence and Risk Factors of Reinfection with HCV after Treatment in People Living with HIV. Viruses 2022; 14:v14020439. [PMID: 35216032 PMCID: PMC8874599 DOI: 10.3390/v14020439] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 02/08/2022] [Accepted: 02/17/2022] [Indexed: 02/04/2023] Open
Abstract
Infection with hepatitis C virus (HCV) does not induce protective immunity, and re-exposure to HCV can reinfect the population engaging in high-risk behavior. An increasing incidence of acute hepatitis C infection in people living with HIV (PLWH) has been described in recent years. This retrospective cohort study was conducted in PLWH who completed HCV therapy between June 2009 and June 2020 at an HIV care hospital, to analyze their basic characteristics and risky behavior. Of 2419 patients, 639 were diagnosed with HCV infection and 516 completed the HCV therapy with a sustained virologic response. In total, 59 patients (11.4%) were reinfected with acute hepatitis C, and the median time to reinfection was 85.3 weeks (IQR: 57–150). The incidence of reinfection was 6.7 cases/100 person-years. The factors associated with reinfection were being male (AHR, 8.02; 95% CI 1.08–59.49), DAA (direct-acting antiviral) treatment (AHR, 2.23; 95% CI 1.04–4.79), liver cirrhosis (AHR, 3.94; 95% CI 1.09–14.22), heroin dependency (AHR: 7.41; 95% CI 3.37–14.3), and HIV viral loads <50 copies/mL at the follow-up (AHR: 0.47, 95% CI 0.24–0.93) in the subgroup of people who inject drugs (PWID). Amphetamine abuse (AHR: 20.17; 95% CI 2.36–172.52) was the dominant factor in the subgroup of men who have sex with men (MSM). Our study suggests that education and behavioral interventions are needed in this population to prevent reinfection.
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Affiliation(s)
- Chien-Yu Cheng
- Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan City 330, Taiwan; (C.-Y.C.); (Y.-C.L.); (C.-P.C.); (S.-H.C.)
- Institute of Public Health, School of Medicine, National Yang-Ming Chiao Tung University, Taipei City 112, Taiwan
| | - Shin-Yen Ku
- Department of Nursing, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan City 330, Taiwan;
| | - Yi-Chun Lin
- Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan City 330, Taiwan; (C.-Y.C.); (Y.-C.L.); (C.-P.C.); (S.-H.C.)
| | - Cheng-Pin Chen
- Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan City 330, Taiwan; (C.-Y.C.); (Y.-C.L.); (C.-P.C.); (S.-H.C.)
- School of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei City 112, Taiwan
| | - Shu-Hsing Cheng
- Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan City 330, Taiwan; (C.-Y.C.); (Y.-C.L.); (C.-P.C.); (S.-H.C.)
- School of Public Health, Taipei Medical University, Taipei City 110, Taiwan
| | - I-Feng Lin
- Institute of Public Health, School of Medicine, National Yang-Ming Chiao Tung University, Taipei City 112, Taiwan
- Correspondence:
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32
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Abstract
In the 1970s, an unknown virus was suspected for documented cases of transfusion-associated hepatitis, a phenomenon called non-A, non-B hepatitis. In 1989, the infectious transmissible agent was identified and named hepatitis C virus (HCV) and, soon enough, the first diagnostic HCV antibody test was developed, which led to a dramatic decrease in new infections. Today, HCV infection remains a global health burden and a major cause of liver cirrhosis, hepatocellular carcinoma and liver transplantation. However, tremendous advances have been made over the decades, and HCV became the first curable, chronic viral infection. The introduction of direct antiviral agents revolutionized antiviral treatment, leading to viral eradication in more than 98% of all patients infected with HCV. This Perspective discusses the history of HCV research, which reads like a role model for successful translational research: starting from a clinical observation, specific therapeutic agents were developed, which finally were implemented in national and global elimination programmes.
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Affiliation(s)
- Michael P. Manns
- grid.10423.340000 0000 9529 9877Hannover Medical School, Hannover, Germany
| | - Benjamin Maasoumy
- grid.10423.340000 0000 9529 9877Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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33
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Wyles DL, Kang M, Matining RM, Murphy RL, Peters MG. Continued Low Rates of Hepatitis C Virus (HCV) Recurrence in HCV/HIV- and HCV-Infected Participants Who Achieved Sustained Virologic Response After Direct-Acting Antiviral Treatment: Final Results From the AIDS Clinical Trials Group A5320 Viral Hepatitis C Infection Long-term Cohort Study (V-HICS). Open Forum Infect Dis 2021; 8:ofab511. [PMID: 34926713 PMCID: PMC8677564 DOI: 10.1093/ofid/ofab511] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 10/12/2021] [Indexed: 01/03/2023] Open
Abstract
Final results from the long-term Viral Hepatitis C Infection Long-term Cohort Study (V-HICS) found low rates of hepatitis C virus (HCV) recurrence after direct-acting antiviral therapy in both HCV/human immunodeficiency virus (HIV)-coinfected (0.67/100 person-years) and HCV-infected (0.2/100 person-years) groups with >500 person-years of follow-up. Confirmed reinfections were in participants with HIV who reported high-risk behaviors.
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Affiliation(s)
- David L Wyles
- Department of Medicine, Denver Health Medical Center, Denver Colorado, USA
| | - Minhee Kang
- Center for Biostatistics in AIDS Research in the Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Roy M Matining
- Center for Biostatistics in AIDS Research in the Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Robert L Murphy
- Department of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Marion G Peters
- Department of Medicine, University of California, San Francisco, San Francisco, California, USA
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34
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Huang MH, Sun HY, Ho SY, Chang SY, Hsieh SM, Sheng WH, Chuang YC, Huang YS, Su LH, Liu WC, Su YC, Hung CC. Recently acquired hepatitis C virus infection among people living with human immunodeficiency virus at a university hospital in Taiwan. World J Gastroenterol 2021; 27:6277-6289. [PMID: 34712032 PMCID: PMC8515799 DOI: 10.3748/wjg.v27.i37.6277] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 07/13/2021] [Accepted: 09/02/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Little is known about the engagement in hepatitis C virus (HCV) care and completion of HCV treatment in people living with human immunodeficiency virus (HIV) (PLWH) who have HCV coinfection in the Asia-Pacific region. Examining the HCV care cascade can identify barriers to the completion of HCV treatment and facilitate achievement of HCV micro-elimination in PLWH.
AIM To investigate the care cascade of incident HCV infections among PLWH in Taiwan.
METHODS PLWH with incident HCV infections, defined as HCV seroconversion, were retrospectively identified by sequential anti-HCV testing of all archived blood samples at National Taiwan University Hospital between 2011 and 2018. All PLWH with incident HCV infections were followed until December 31, 2019. The care cascade of HCV examined included all incident HCV-infected patients, the percentages of anti-HCV antibodies detected by HIV-treating physicians in clinical care, plasma HCV RNA load tested, HCV RNA positivity diagnosed, referral to treatment assessment made, anti-HCV treatment initiated, and sustained virologic response achieved. Those who had HCV seroconversion during the interferon (IFN) era (2011–2016) and the direct-acting antiviral (DAA) era (2017–2018) were analyzed separately. The duration of HCV viremia—from the date of seroconversion to viral clearance by treatments or until the end of observation—and the incidence of sexually transmitted infections (STIs) during the HCV viremic period were estimated.
RESULTS During the study period, 287 of 3495 (8.2%) PLWH (92.3% being men who have sex with men) who were HCV-seronegative at baseline developed HCV seroconversion by retrospective testing of all archived blood samples. Of the 287 incident HCV infections, 277 (96.5%) had anti-HCV antibodies detected by HIV-treating physicians, 270 (94.1%) had plasma HCV RNA determined and 251 (87.5%) tested positive for HCV RNA. Of those with HCV viremia, 226 (78.7%) were referred to treatment assessment, 215 (74.9%) initiated anti-HCV treatment, and 202 (70.4%) achieved viral clearance. Compared with that in the IFN era, the median interval from HCV seroconversion by retrospective testing to detection of HCV seropositivity by HIV-treating physicians was significantly shorter in the DAA era {179 d [interquartile range (IQR) 87-434] vs 92 d (IQR 57-173); P < 0.001}. The incidence rate of STIs in the DAA vs the IFN era was 50.5 per 100 person-years of follow-up (PYFU) and 38.5 per 100 PYFU, respectively, with an incidence rate ratio of 1.31 (95% confidence interval 0.96-1.77), while the duration of HCV viremia was 380 d (IQR 274-554) and 735 d (IQR 391-1447) (P < 0.001), respectively.
CONCLUSION While anti-HCV therapies are effective in achieving viral clearance, our study suggests more efforts are needed to expedite the linkage of PLWH diagnosed with incident HCV infections to HCV treatment.
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Affiliation(s)
- Miao-Hui Huang
- Department of Internal Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien 970410, Taiwan
| | - Hsin-Yun Sun
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100008, Taiwan
| | - Shu-Yuan Ho
- Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100008, Taiwan
| | - Sui-Yuan Chang
- Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100008, Taiwan
- Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei 100233, Taiwan
| | - Szu-Min Hsieh
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100008, Taiwan
| | - Wang-Huei Sheng
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100008, Taiwan
| | - Yu-Chung Chuang
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100008, Taiwan
| | - Yu-Shan Huang
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100008, Taiwan
| | - Li-Hsin Su
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100008, Taiwan
| | - Wen-Chun Liu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100008, Taiwan
| | - Yi-Ching Su
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100008, Taiwan
| | - Chien-Ching Hung
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100008, Taiwan
- Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine, Taipei 100233, Taiwan
- Department of Medical Research, China Medical University Hospital and China Medical University, Taichung 404394, Taiwan
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Rockstroh JK. Hepatitis C Micro-elimination in Human Immunodeficiency Virus-Coinfected Men Who Have Sex With Men: A Low Hanging Fruit? Clin Infect Dis 2021; 73:e2203-e2204. [PMID: 32756972 DOI: 10.1093/cid/ciaa1113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Accepted: 07/29/2020] [Indexed: 11/13/2022] Open
Affiliation(s)
- Jürgen Kurt Rockstroh
- Department of Medicine I, University Hospital Bonn, Bonn, Germany.,German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany
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36
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Liu CH, Kao JH. Last Mile to Microelimination of Hepatitis C Virus Infection Among People Living With Human Immunodeficiency Virus. Clin Infect Dis 2021; 73:e2172-e2174. [PMID: 33005954 DOI: 10.1093/cid/ciaa1499] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 09/29/2020] [Indexed: 04/16/2025] Open
Affiliation(s)
- Chen-Hua Liu
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Douliou, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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37
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Simoncini GM, Hou Q, Carlson K, Buchacz K, Tedaldi E, Palella F, Durham M, Li J. Disparities in Treatment with Direct-Acting Hepatitis C Virus Antivirals Persist Among Adults Coinfected with HIV and Hepatitis C Virus in US Clinics, 2010-2018. AIDS Patient Care STDS 2021; 35:392-400. [PMID: 34623891 PMCID: PMC10951816 DOI: 10.1089/apc.2021.0087] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection carries substantial risk for all-cause mortality and liver-related morbidity and mortality, yet many persons coinfected with HIV/HCV remain untreated for HCV. We explored demographic, clinical, and sociodemographic factors among participants in routine HIV care associated with prescription of direct-acting antivirals (DAAs). The HIV Outpatient Study (HOPS) is an ongoing longitudinal cohort study of persons with HIV in care at participating clinics since 1993. There are currently eight study sites in six US cities. We analyzed medical records data of HOPS participants diagnosed with HCV since June 2010. Sustained virological response (SVR) was documented with first undetectable HCV viral load (VL). We assessed factors associated with being prescribed DAAs by multi-variable logistic regression and described the cumulative rate of SVR. Among 306 eligible participants, 131 (43%) were prescribed DAA therapy. Factors associated with greater odds of being prescribed DAA were older age, private health insurance, higher CD4 cell count, being a person who injects drugs, and receiving care at publicly funded sites (p < 0.05). Of 127 (97%) participants with at least 1 follow-up HCV VL, 110 (87%) achieved SVR at 12 weeks. Of the total 131 participants, 123 (94%) eventually achieved SVR. Less than half of HIV/HCV coinfected patients in HOPS have been prescribed DAAs. Interventions are needed to address deficits in DAA prescription, including among patients with public or no health insurance, younger age, and lower CD4 cell count.
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Affiliation(s)
- Gina M. Simoncini
- Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA
| | | | | | - Kate Buchacz
- Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Ellen Tedaldi
- Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA
| | - Frank Palella
- Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Marcus Durham
- Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Jun Li
- Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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38
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Factors associated with testing for HIV and hepatitis C among behaviorally vulnerable men in Germany: a cross-sectional analysis upon enrollment into an observational cohort. AIDS Res Ther 2021; 18:52. [PMID: 34399787 PMCID: PMC8365908 DOI: 10.1186/s12981-021-00378-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 08/04/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND HIV and hepatitis C virus (HCV) have shared routes of transmission among men who have sex with men (MSM). Routine testing facilitates early diagnosis and treatment, thereby preventing morbidity and onward transmission. We evaluated factors associated with HIV and HCV testing in a behaviorally vulnerable cohort of predominantly MSM. METHODS From June 2018 through June 2019, the BRAHMS study enrolled adults at ten German outpatient clinics that serve gender and sexual minority populations. Participants completed behavioral questionnaires that captured prior experience with HIV and HCV testing. Multivariable robust Poisson regression was used to evaluate factors potentially associated with testing in the previous 6 months. RESULTS Among 1017 participants with median age 33 (interquartile range 28-39) years, 1001 (98.4%) reported any lifetime history of HIV testing and 787 (77.4%) reported any HCV testing, including 16 (1.6%) known to be living with HCV. Testing within the last 6 months was reported by 921 (90.6%) and 513 (50.4%) for HIV and HCV, respectively. Recent HIV testing was more common among participants with higher education level and recent HCV testing. Recent HCV testing was more common among participants with non-cisgender identity, lifetime history of illicit drug use, hepatitis B immunity or infection, and recent HIV testing. CONCLUSION Prior testing for HIV was common in this cohort, but interventions are needed to improve HCV risk stratification and access to testing. HIV testing infrastructure can be successfully leveraged to support HCV testing, but differentiated preventive care delivery is needed for some vulnerable populations.
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39
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Newsum AM, Matser A, Schinkel J, van der Valk M, Brinkman K, van Eeden A, Lauw FN, Rijnders BJA, van de Laar TJW, van de Kerkhof M, Smit C, Boyd A, Arends JE, Prins M. Incidence of HCV Reinfection Among HIV-Positive MSM and Its Association With Sexual Risk Behavior: A Longitudinal Analysis. Clin Infect Dis 2021; 73:460-467. [PMID: 32459339 DOI: 10.1093/cid/ciaa645] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Accepted: 05/21/2020] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) are at high risk of hepatitis C virus (HCV) reinfection following clearance of HCV, but risk factors specifically for reinfection have never been comprehensively assessed. METHODS Using data from a prospective observational cohort study among HIV-positive MSM with an acute HCV infection (MOSAIC), the incidence of HCV reinfection following spontaneous clearance or successful treatment was assessed. A univariable Bayesian exponential survival model was used to identify risk factors associated with HCV reinfection. RESULTS In total, 122 HIV-positive MSM who had a spontaneously cleared or successfully treated HCV infection between 2003 and 2017 were included. During a median follow-up of 1.4 years (interquartile range [IQR] 0.5-3.8), 34 HCV reinfections were observed in 28 patients. The incidence of HCV reinfection was 11.5/100 person-years and among those with reinfection, median time to reinfection was 1.3 years (IQR 0.6-2.7). HCV reinfection was associated with receptive condomless anal intercourse, sharing of sex toys, group sex, anal rinsing before sex, ≥10 casual sex partners in the last 6 months, nadir CD4 cell count <200 cells/mm3, and recent CD4 cell count <500 cells/mm3. CONCLUSIONS Incidence of HCV reinfection was high and strongly associated with sexual risk behavior, highlighting the need for interventions to reduce risk behavior and prevent HCV reinfections among HIV-positive MSM.
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Affiliation(s)
- Astrid M Newsum
- Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands.,Division of Infectious Diseases, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Amy Matser
- Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands
| | - Janke Schinkel
- Department of Medical Microbiology, Laboratory of Clinical Virology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Marc van der Valk
- Division of Infectious Diseases, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Kees Brinkman
- Department of Internal Medicine and Infectious Diseases, OLVG, Amsterdam, the Netherlands
| | - Arne van Eeden
- HIV Focus Center, DC Kliniek Lairesse, Amsterdam, The Netherlands
| | - Fanny N Lauw
- Department of Internal Medicine, Medical Center Jan van Goyen, Amsterdam, the Netherlands
| | - Bart J A Rijnders
- Department of Internal Medicine and Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, the Netherlands
| | - Thijs J W van de Laar
- Department of Donor Medicine Research, Laboratory of Blood-Borne Infections, Sanquin Research, Amsterdam, the Netherlands.,Laboratory of Medical Microbiology, OLVG, Amsterdam, the Netherlands
| | - Marita van de Kerkhof
- Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands.,Division of Infectious Diseases, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Colette Smit
- Stichting HIV Monitoring, Amsterdam, the Netherlands
| | - Anders Boyd
- Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands.,Stichting HIV Monitoring, Amsterdam, the Netherlands
| | - Joop E Arends
- Department of Internal Medicine, Section Infectious Diseases, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Maria Prins
- Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands.,Division of Infectious Diseases, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
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40
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Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I, Reno H, Zenilman JM, Bolan GA. Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep 2021; 70:1-187. [PMID: 34292926 PMCID: PMC8344968 DOI: 10.15585/mmwr.rr7004a1] [Citation(s) in RCA: 1053] [Impact Index Per Article: 263.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
These guidelines for the treatment of persons who have or are at risk for sexually transmitted infections (STIs) were updated by CDC after consultation with professionals knowledgeable in the field of STIs who met in Atlanta, Georgia, June 11-14, 2019. The information in this report updates the 2015 guidelines. These guidelines discuss 1) updated recommendations for treatment of Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; 2) addition of metronidazole to the recommended treatment regimen for pelvic inflammatory disease; 3) alternative treatment options for bacterial vaginosis; 4) management of Mycoplasma genitalium; 5) human papillomavirus vaccine recommendations and counseling messages; 6) expanded risk factors for syphilis testing among pregnant women; 7) one-time testing for hepatitis C infection; 8) evaluation of men who have sex with men after sexual assault; and 9) two-step testing for serologic diagnosis of genital herpes simplex virus. Physicians and other health care providers can use these guidelines to assist in prevention and treatment of STIs.
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41
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Koopsen J, Parker E, Han AX, van de Laar T, Russell C, Hoornenborg E, Prins M, van der Valk M, Schinkel J. Hepatitis C Virus Transmission Among Men Who Have Sex With Men in Amsterdam: External Introductions May Complicate Microelimination Efforts. Clin Infect Dis 2021; 72:e1056-e1063. [PMID: 33289036 DOI: 10.1093/cid/ciaa1830] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND It is unclear whether unrestricted access and high uptake of direct-acting antivirals (DAAs) is sufficient to eliminate hepatitis C virus (HCV) in high-risk populations such as men who have sex with men (MSM). This study presents historic trends and current dynamics of HCV transmission among MSM in Amsterdam based on sequence data collected between 1994 and 2019. METHODS Hypervariable region 1 sequences of 232 primary HCV infections and 56 reinfections were obtained from 244 MSM in care in Amsterdam. Maximum-likelihood phylogenies were constructed for HCV genotypes separately, and time-scaled phylogenies were constructed using a Bayesian coalescent approach. Transmission clusters were determined by Phydelity and trends in the proportion of unclustered sequences over time were evaluated using logistic regression. RESULTS Seventy-six percent (218/288) of sequences were part of 21 transmission clusters and 13 transmission pairs. Transmission cluster sizes ranged from 3 to 44 sequences. Most clusters were introduced between the late 1990s and early 2010s and no new clusters were introduced after 2012. The proportion of unclustered sequences of subtype 1a, the most prevalent subtype in this population, fluctuated between 0% and 20% in 2009-2012, after which an increase occurred from 0% in 2012 to 50% in 2018. CONCLUSIONS The proportion of external introductions of HCV infections among MSM in Amsterdam has recently increased, coinciding with high DAA uptake. Frequent international transmission events will likely complicate local microelimination efforts. Therefore, international collaboration combined with international scale-up of prevention, testing, and treatment of HCV infections (including reinfections) is warranted, in particular for local microelimination efforts.
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Affiliation(s)
- Jelle Koopsen
- Department of Medical Microbiology, Laboratory of Applied Evolutionary Biology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Edyth Parker
- Department of Medical Microbiology, Laboratory of Applied Evolutionary Biology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.,Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Alvin X Han
- Department of Medical Microbiology, Laboratory of Applied Evolutionary Biology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Thijs van de Laar
- Department of Donor Medicine Research, Laboratory of Blood-borne Infections, Sanquin Research, Amsterdam, The Netherlands.,Laboratory of Medical Microbiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | - Colin Russell
- Department of Medical Microbiology, Laboratory of Applied Evolutionary Biology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Elske Hoornenborg
- Sexually Transmitted Infections Outpatient Clinic, Public Health Service of Amsterdam, Amsterdam, The Netherlands.,Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, The Netherlands
| | - Maria Prins
- Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, The Netherlands.,Division of Infectious Diseases, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Marc van der Valk
- Division of Infectious Diseases, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Janke Schinkel
- Department of Medical Microbiology, Section of Clinical Virology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
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Ohata PJ, Su Lwin HM, Han WM, Khwairakpam G, Tangkijvanich P, Matthews GV, Avihingsanon A. Elimination of hepatitis C among HIV-positive population in Asia: old and new challenges. Future Virol 2021. [DOI: 10.2217/fvl-2021-0015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Hepatitis C virus (HCV) prevalence is high among people living with HIV co-infected with HCV, people who inject drugs, men who have sex with men and inmates in correctional settings. The barriers to eliminate HCV among these key populations include diagnosis challenges, lack of awareness, discrimination and stigmatization. In addition, scaling up of HCV treatment has been a challenge in Asia–Pacific with the lack of national policies, targets and unavailability of appropriate direct-acting antivirals regimens. In order to achieve HCV micro elimination within these high-risk populations, novel strategies to improve the cascade of care from diagnosis to treatment with direct-acting antivirals, complemented by behavioral change interventions, harm reduction services for people who inject drugs, civil society led advocacy and policies from the government, will be necessary.
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Affiliation(s)
- Pirapon June Ohata
- HIV-NAT, Thai Red Cross – AIDS Research Centre, 104 Ratchadamri Road, Pathumwan, Bangkok, 10330, Thailand
| | - Hay Mar Su Lwin
- HIV-NAT, Thai Red Cross – AIDS Research Centre, 104 Ratchadamri Road, Pathumwan, Bangkok, 10330, Thailand
| | - Win Min Han
- HIV-NAT, Thai Red Cross – AIDS Research Centre, 104 Ratchadamri Road, Pathumwan, Bangkok, 10330, Thailand
| | - Giten Khwairakpam
- TREAT Asia, Exchange Tower, 388 Sukhumvit Road, Suite 2104, Klongtoey, Bangkok, 10110, Thailand
| | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis & Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand
| | - Gail V Matthews
- The Kirby Institute, University of New South Wales, NSW, Sydney, 2052, Australia
| | - Anchalee Avihingsanon
- HIV-NAT, Thai Red Cross – AIDS Research Centre, 104 Ratchadamri Road, Pathumwan, Bangkok, 10330, Thailand
- Tuberculosis Research Unit (TB RU), Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand
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Sarrazin C, Boesecke C, Golsabahi‐Broclawski S, Moog G, Negro F, Silaidos C, Patel P, Lohmann K, Spinner CD, Walcher S, Wedemeyer H, Wörns M. Hepatitis C virus: Current steps toward elimination in Germany and barriers to reaching the 2030 goal. Health Sci Rep 2021; 4:e290. [PMID: 34136654 PMCID: PMC8177898 DOI: 10.1002/hsr2.290] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 02/24/2021] [Accepted: 04/13/2021] [Indexed: 11/25/2022] Open
Abstract
Hepatitis C virus (HCV) affects over 70 million people globally, with an estimated 399 000 HCV-related deaths in 2016. The World Health Organization (WHO) has set a goal to eliminate HCV by 2030. Despite the availability of direct-acting antivirals-highly effective and well-tolerated therapies for HCV-many patients infected with HCV in Germany have not initiated treatment, including a majority of those who are aware of their positive diagnosis. Barriers to screening, diagnosis, and treatment are major factors taking many countries off track for HCV elimination by 2030. Identifying country-specific barriers and challenges, particularly in at-risk populations such as people who inject drugs or men who have sex with men, has the potential to create tailored programs and strategies to increase access to screening or treatment and engage at-risk populations. This review aims to report the current steps toward HCV elimination in Germany, the country-specific barriers and challenges that will potentially prevent reaching the 2030 HCV elimination goal and describe good practice examples to overcome these barriers.
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Affiliation(s)
- Christoph Sarrazin
- Department of Internal Medicine and Liver CenterSt. Josefs‐Hospital Wiesbaden and Viral Hepatitis Research Group, Goethe‐University Hospital FrankfurtFrankfurtGermany
| | - Christoph Boesecke
- Department of Medicine IUniversity Hospital BonnBonnGermany
- German Centre for Infection Research (DZIF)Partner‐site Bonn‐CologneBonnGermany
| | | | - Gero Moog
- Gastroenterologische Praxis im MarienkrankenhausKasselGermany
| | - Francesco Negro
- Divisions of Gastroenterology and Hepatology and of Clinical PathologyGeneva University HospitalsGenevaSwitzerland
| | | | | | | | - Christoph D. Spinner
- Department of Internal Medicine II, School of Medicine, University Hospital Rechts der IsarTechnical University of MunichMunichGermany
- German Centre for Infection Research (DZIF), Partner Site MunichMunichGermany
| | | | - Heiner Wedemeyer
- Department of GastroenterologyHepatology and Endocrinology, Hannover Medical SchoolHannoverGermany
- Leberstiftungs‐GmbH DeutschlandHannoverGermany
| | - Marcus‐Alexander Wörns
- First Department of MedicineUniversity Medical Centre of the Johannes Gutenberg‐UniversityMainzGermany
- Cirrhosis Centre Mainz (CCM)University Medical Centre of the Johannes Gutenberg‐UniversityMainzGermany
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Impact of Sexualized Substance Use and Other Risk Practices on HCV Microelimination in gbMSM Living with HIV: Urgent Need for Targeted Strategies. Results of a Retrospective Cohort Study. Infect Dis Ther 2021; 10:1253-1266. [PMID: 33914265 PMCID: PMC8322221 DOI: 10.1007/s40121-021-00448-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 04/10/2021] [Indexed: 10/28/2022] Open
Abstract
INTRODUCTION The objective of the present study is to describe the incidence of recently acquired hepatitis C (RAHCV) in a large cohort of people living with HIV (PLWHIV) and sexualized drug use and other related risk behaviours. METHODS Observational study including all PLWHIV with a RAHCV episode between June 2005 and December 2019 at the Hospital Clinic of Barcelona, Spain. Incidence of RAHCV was determined per person calendar year (py) in those patients who were HCV RNA negative. Data were collected on high-risk sexual practices for HCV transmission focused on gay, bisexual and other men having sex with men (gbMSM). RESULTS A total of 340 RAHCV were diagnosed in 290 PLWHIV; 274 (94%) of them were gbMSM and developed 324 RAHCV, mainly since 2010 (90%). Overall incidence rate (IR) of RAHCV in gbMSM was 0.10 py (95% CI 0.09-0.11), with a 40% decreased observed since 2017 (IR 0.06, 95% CI 0.03-0.09 in 2019). Sixty reinfections were detected in 50 gbMSM (n = 244, 20%). The overall reinfection IR was 0.17 per py (95% CI 0.12-0.23) and the proportion of reinfection among total RAHCV increased to 47% cases in 2019, mainly in patients engaged in sexualized substance use (76%), unprotected anal intercourse (94%), sex partying (80%), fisting (43%), slamming (14%) and 60% of concomitant sexually transmitted infections (STIs). CONCLUSIONS Despite RAHCV incidence decline in our cohort since 2017, HCV reinfection increased. High sexualized substance use and other risk behaviours are described in this context, indicating the need for public health tailored strategies to reduce this transmission and achieve HCV microelimination in gbMSM living with HIV.
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Ingiliz P, Wehmeyer MH, Boesecke C, Schulze Zur Wiesch J, Schewe K, Lutz T, Baumgarten A, Simon KG, Hueppe D, Rockstroh JK, Mauss S, Christensen S. Reinfection With the Hepatitis C Virus in Men Who Have Sex With Men After Successful Treatment With Direct-acting Antivirals in Germany: Current Incidence Rates, Compared With Rates During the Interferon Era. Clin Infect Dis 2021; 71:1248-1254. [PMID: 31562816 DOI: 10.1093/cid/ciz949] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Accepted: 09/23/2019] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Micro-elimination of the hepatitis C virus (HCV) includes treatment in populations at risk of ongoing HCV transmission, such as men who have sex with men (MSM) or people who inject drugs (PWID). We analyzed the HCV reinfection incidence rates of participants in the German hepatitis C cohort (GECCO) and compared our data to previous findings from the interferon era. METHODS Patients with HCV reinfections in the multi-centric GECCO cohort were compared to patients in whom no reinfection occurred. The HCV reinfection incidence rate in MSM was also compared to the incidence rate in the interferon era (using data from the European Acquired Immunodeficiency Syndrome Treatment Network [NEAT]). RESULTS Between January 2014 and April 2018, 48 HCV reinfections occurred in 2298 individuals (2%), with 2346 cured HCV episodes. The median time to reinfection was 500 days (range 16-1160) and the overall HCV reinfection incidence rate was 1.89 per 100 person-years (py; 95% confidence interval [CI], 1.41-2.48). In a multivariate analysis, the transmission risk in MSM was the only independent risk factor of HCV reinfection (odds ratio, 39.3; 95% CI, 4.57-334.40; P = .001). The incidence rate in MSM was 9.02 (95% CI, 6.48-12.26) per 100 py, compared to 1.14 per 100 py in PWID (95% CI, .56-2.09). The incidence rate for a first HCV reinfection in MSM was similar in the direct-acting antiviral era, compared to the interferon era, with a hazard ratio of 1.05 (95% CI, .64-1.74; P = .831). CONCLUSIONS HCV reinfection remains a frequent finding among MSM in Germany. In addition to behavioral interventions, early HCV treatment and retreatment should be implemented for this subgroup to prevent HCV transmission.
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Affiliation(s)
- Patrick Ingiliz
- Center for Infectiology, Berlin, Germany.,Department of Gastroenterology and Hepatology, Charité University Medical Center, Berlin, Germany
| | - Malte H Wehmeyer
- Medical Department, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christoph Boesecke
- Department of Medicine I, University Hospital Bonn, Bonn, Germany.,German Centre for Infection Research, Partner Site Cologne-Bonn, Bonn, Germany.,Infectious Diseases, European Acquired Immunodeficiency Syndrome Treatment Network, Brussels, Belgium
| | - Julian Schulze Zur Wiesch
- Medical Department, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.,German Centre for Infection Research, Partner Site Cologne-Bonn, Bonn, Germany
| | - Knud Schewe
- Infectiology Center Hamburg Study Center, Hamburg, Germany
| | | | | | | | | | - Juergen K Rockstroh
- Department of Medicine I, University Hospital Bonn, Bonn, Germany.,German Centre for Infection Research, Partner Site Cologne-Bonn, Bonn, Germany.,Infectious Diseases, European Acquired Immunodeficiency Syndrome Treatment Network, Brussels, Belgium
| | - Stefan Mauss
- Center for Human Immunodeficiency Virus and Hepatogastroenterology, Duesseldorf, Germany
| | - Stefan Christensen
- Infectious Diseases, Center for Interdisciplinary Medicine, Muenster, Germany.,Department of Gastroenterology and Hepatology, Muenster University Hospital, Muenster, Germany
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46
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Chromy D, Schmidt R, Mandorfer M, Lang GF, Bauer D, Schwabl P, Popow-Kraupp T, Reiberger T, Mayer F. Hepatitis C Virus RNA Is Commonly Detectable in Rectal and Nasal Fluids of Patients With High Viremia. Clin Infect Dis 2021; 71:1292-1299. [PMID: 31562817 DOI: 10.1093/cid/ciz948] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 09/23/2019] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Increasing numbers of hepatitis C virus (HCV) infections among men who have sex with men (MSM) are being observed in the Western world. The actual routes of HCV transmission during high-risk sex practices and associated drug use remain poorly understood. METHODS Forty-seven patients with HCV were prospectively enrolled. Rectal and nasal swabs were collected to quantify HCV-RNA levels within rectal and nasal fluids. Contamination by occult rectal bleeding was excluded by guaiac paper test. Risk behavior was assessed by standardized questionnaires. RESULTS Median age was 41.9 years, 89% were HIV positive (+) (42/47) and 85% (40/47) were male, 58% (23/40) of whom were MSM. Acute HCV infection was diagnosed in 32% (15/47) ,with all patients being HIV+MSM and 93% (14/15) having a documented history of sexually transmitted disease. Thirty-three (70%) patients had ≥1 HCV+ swab sample (HCV+SS; 48%, 22/46 rectal; 62%, 29/47 nasal), and contamination with blood was excluded in all patients. Individuals with HCV+SS had significantly higher serum HCV-RNA levels than patients with HCV-negative SS (6.28 [IQR, 0.85] log IU/mL vs 4.08 [2.45] log IU/mL; P < .001). Using ROC-curve analysis, serum HCV-RNA cutoffs for ruling in/out any HCV+SS were established at 6.02 log IU/mL and 4.02 log IU/mL, respectively. CONCLUSIONS HCV-RNA is commonly detectable in rectal and nasal fluids of both HIV+ and HIV-negative HCV patients with high serum HCV-RNA, independently of the suspected route of HCV transmission. Accordingly, high-risk sex practices and sharing of nasal drug-sniffing "tools" might be important HCV transmission routes, especially in patients with high serum HCV-RNA.
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Affiliation(s)
- David Chromy
- Department of Dermatology, Medical University of Vienna, Vienna, Austria.,Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna HIV and Liver Study Group, Vienna, Austria
| | - Ralf Schmidt
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Mattias Mandorfer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna HIV and Liver Study Group, Vienna, Austria
| | | | - David Bauer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna HIV and Liver Study Group, Vienna, Austria
| | - Philipp Schwabl
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna HIV and Liver Study Group, Vienna, Austria
| | | | - Thomas Reiberger
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.,Vienna HIV and Liver Study Group, Vienna, Austria
| | - Florian Mayer
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
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47
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Rockstroh JK, Boesecke C. Hepatitis C Virus Treatment as Prevention: Challenges and Opportunities in Men Who Have Sex With Men. J Infect Dis 2021; 222:S782-S788. [PMID: 33245348 DOI: 10.1093/infdis/jiaa096] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Since 2002, a global epidemic of acute hepatitis C virus (HCV) infection has been noted in men who have sex with men (MSM). Transmission of HCV, particularly in the context of traumatic sex practices that increase the risk of blood-blood contacts (eg, anal sex and fisting), was initially found in human immunodeficiency virus (HIV)-coinfected and more recently in HIV-uninfected MSM, especially those receiving pre-exposure prophylaxis (PrEP). Early HCV treatment with all-oral direct-acting antiviral combination therapy has been associated with very high HCV cure rates of up to 100%. Indeed, immediate treatment of recently acquired HCV directly after new HCV diagnosis, or after 4 weeks if no 2-log10 drop in HCV RNA level occurs, promises rapid HCV elimination. Reports from the Netherlands, Switzerland, and the United Kingdom all show that with increased treatment uptake in this particular patient group, dramatic reductions in new HCV infections can be achieved. A general consensus on how to best screen for and manage acute HCV infections, along with broad access to rapid HCV therapy initiation, is crucial to attaining HCV elimination, a goal that is challenged by high HCV reinfection rates among MSM.
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Affiliation(s)
- Jürgen Kurt Rockstroh
- Department of Medicine I, University Hospital Bonn, Germany.,German Centre for Infection Research, partner site Bonn-Cologne, Bonn, Germany
| | - Christoph Boesecke
- Department of Medicine I, University Hospital Bonn, Germany.,German Centre for Infection Research, partner site Bonn-Cologne, Bonn, Germany
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48
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Abstract
PURPOSE OF REVIEW The WHO has set ambitious targets for hepatitis C virus (HCV) elimination by 2030. In this review, we explore the possibility of HCV micro-elimination in HIV-positive (+) MSM, discussing strategies for reducing acute HCV incidence and the likely interventions required to meet these targets. RECENT FINDINGS With wider availability of directly acting antivirals (DAAs) in recent years, reductions in acute HCV incidence have been reported in some cohorts of HIV+ MSM. Recent evidence demonstrates that treatment in early infection is well tolerated, cost effective and may reduce the risk of onward transmission. Modelling studies suggest that to reduce incidence, a combination approach including behavioural interventions and access to early treatment, targeting both HIV+ and negative high-risk groups, will be required. HCV vaccine trials have not yet demonstrated efficacy in human studies, however phase one and two studies are ongoing. SUMMARY Some progress towards the WHO HCV elimination targets has been reported. Achieving sustained HCV elimination is likely to require a combination approach including early access to DAAs in acute infection and reinfection, validated and reproducible behavioural interventions and an efficacious HCV vaccine.
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49
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Adu PA, Rossi C, Binka M, Wong S, Wilton J, Wong J, Butt ZA, Bartlett S, Jeong D, Pearce M, Darvishian M, Yu A, Alvarez M, Velásquez García HA, Krajden M, Janjua NZ. HCV reinfection rates after cure or spontaneous clearance among HIV-infected and uninfected men who have sex with men. Liver Int 2021; 41:482-493. [PMID: 33305525 DOI: 10.1111/liv.14762] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 11/13/2020] [Accepted: 11/26/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Hepatitis C virus (HCV) reinfection among high-risk groups threatens HCV elimination goals. We assessed HCV reinfection rates among men who have sex with men (MSM) in British Columbia (BC), Canada. METHODS We used data from the BC Hepatitis Testers Cohort, which includes nearly 1.7 million individuals tested for HCV or HIV in BC. MSM who had either achieved sustained virologic response (SVR) after successful HCV treatment, or spontaneous clearance (SC) and had ≥1 subsequent HCV RNA measurement, were followed from the date of SVR or SC until the earliest of reinfection, death, or last HCV RNA measurement. Predictors of reinfection were identified by Cox proportional modelling. The earliest study start date was 6 November 1997 and latest end date was 13 April 2018. RESULTS Of 1349 HCV-positive MSM who met the inclusion criteria, 493 had SC while 856 achieved SVR. 349 (25.65%) had HIV coinfection. We identified 98 reinfections during 5203 person-years (PYs) yielding a reinfection rate of 1.88/100PYs. The reinfection rate among SC (2.74/100PYs) was more than twice that of those with SVR (1.03/100 PYs). Problematic alcohol use (aHR 1.73, 95% CI 1.003-2.92), injection drug use (aHR 2.60, 95% CI 1.57-4.29) and HIV coinfection (aHR 2.04, 95% CI 1.29-3.23) were associated with increased risk of HCV reinfection. Mental health counselling history (aHR 0.24, 95% CI 0.13-0.46) was associated with reduced HCV reinfection risk. CONCLUSIONS There is the need to engage MSM in harm reduction and prevention services following treatment to reduce reinfection risk.
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Affiliation(s)
- Prince A Adu
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Carmine Rossi
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,Analysis Group, Inc., Montreal, Quebec, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Mawuena Binka
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Stanley Wong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - James Wilton
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Jason Wong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Zahid A Butt
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.,School of Public Health and Health Systems, University of Waterloo, Waterloo, Ontario, Canada
| | - Sofia Bartlett
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Dahn Jeong
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Margo Pearce
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Maryam Darvishian
- British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada
| | - Amanda Yu
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | - Maria Alvarez
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada
| | | | - Mel Krajden
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Naveed Z Janjua
- British Columbia Centre for Disease Control, Vancouver, British Columbia, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
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50
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Nguyen T, Valantin MA, Delaugerre C, Amiel C, Netzer E, L'Yavanc T, Ohayon M, Valin N, Day N, Kreplak G, Pialoux G, Calvez V, Molina JM, Marcelin AG, Todesco E. Low level of baseline resistance in recently HCV-infected men who have sex with men with high-risk behaviours. J Glob Antimicrob Resist 2021; 24:311-315. [PMID: 33540082 DOI: 10.1016/j.jgar.2021.01.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 12/11/2020] [Accepted: 01/23/2021] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVES Presence of baseline hepatitis C virus (HCV) resistance-associated substitutions (RASs) can impair treatment outcome of direct-acting antivirals. We investigated the prevalence of pre-treatment HCV resistance among recently HCV-infected men who have sex with men (MSM) with high risk behaviours, either human immunodeficiency virus (HIV) co-infected or at high risk of HIV acquisition and under pre-exposure prophylaxis (PrEP). METHODS NS5A and NS3 fragments were deep sequenced on pre-treatment samples of 72 subjects using Illumina MiSeq paired-end sequencing technology. Ultra-deep sequencing data were analysed by SmartGene® platform. RASs mentioned in the literature were analysed and interpreted depending on genotype (GT) at 10% cut-off. RESULTS HCV genotyping showed 36 (50.0%) GT1a, 31 (43.1%) GT4d and 5 (6.9%) GT3a infections. Fifty-five patients (76.4%) were co-infected with HIV and 15 (20.8%) received PrEP. In GT1a viruses, NS3 RASs were found in 4/30 viruses (13.3%; S122 G/N, R155 K and I170 V) and Q80 K polymorphism was present in 14/30 viruses (46.7%). No NS3 RASs were detected in GT4d and GT3a viruses. NS5A RASs were detected in 3/36 GT1a viruses (8.3%; Q30E/R, L31 M and H58 L). NS5A subtype-specific polymorphisms L30R and T58 P were found at high frequencies in 31/31 (100%) and 16/31 (51.6%) GT4d viruses, respectively. One RAS M31 L was also observed along with the polymorphisms L30R and T58 P. No NS5A RASs were detected in GT3a viruses. CONCLUSION A low level of RASs to NS3 and NS5A inhibitors in pre-treatment samples was detected in the study population. Our findings reassure the clinical management of HCV infection in this high-risk population.
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Affiliation(s)
- Thuy Nguyen
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie, F-75013 Paris, France
| | - Marc-Antoine Valantin
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Services de maladies infectieuses et tropicales, F-75013 Paris, France
| | - Constance Delaugerre
- AP-HP, Hôpital Saint-Louis, Laboratoire de virologie, Paris, France; INSERM UMR 941, Université de Paris Diderot, Paris, France
| | - Corinne Amiel
- Sorbonne Université, Centre d'Immunologie et de Maladies Infectieuses (CIMI) UMRS CR7, Persistent Viral Infection (PVI) Team, Inserm U1135, AP-HP, Groupe Hospitalier Paris Est, Hôpital Tenon, Laboratoire de virologie, F-75020 Paris, France
| | | | - Thomas L'Yavanc
- Centre de santé sexuelle Le 190, Paris, France; Sorbonne Université, AP-HP, Hôpital Tenon, Department of Infectious Diseases, Paris, France
| | - Michel Ohayon
- Centre de santé sexuelle Le 190, Paris, France; Sorbonne Université, AP-HP, Hôpital Tenon, Department of Infectious Diseases, Paris, France
| | - Nadia Valin
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Saint Antoine, Department of Infectious Diseases, F-75012 Paris, France
| | | | | | - Gilles Pialoux
- Sorbonne Université, AP-HP, Hôpital Tenon, Department of Infectious Diseases, Paris, France
| | - Vincent Calvez
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie, F-75013 Paris, France
| | - Jean-Michel Molina
- INSERM UMR 941, Université de Paris Diderot, Paris, France; AP-HP, Hôpital Saint-Louis, Department of Infectious Diseases, Paris, France
| | - Anne-Geneviève Marcelin
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie, F-75013 Paris, France
| | - Eve Todesco
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Laboratoire de virologie, F-75013 Paris, France.
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