EuroSIDA - Clinical and Virological Outcome of European Patients Infected With HIV

Study Overview
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Brief Summary
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The EuroSIDA study is a prospective observational cohort study of 23,000+ patients followed in 100+ clinics in 35 European countries, Israel and Argentina. The study is the largest pan-European cohort study and few studies of a comparable design are available on a global scale. The EuroSIDA study is an ongoing collaboration and patients have been enrolled into the study through 11 cohorts since 1994. The main objective of the study remains the same as in 1994: to prospectively study, clinical, therapeutic, demographic, virological and laboratory data from HIV-1 positive persons across Europe in order to determine their long-term virological, immunological and clinical outcomes. Historically, EuroSIDA has been crucial in reporting key changes in the HIV epidemic, such as the dramatic changes in morbidity and mortality when combination anti-retroviral therapy (cART) was first introduced. As new anti-HCV treatment is introduced to HIV/HCV co-infected patients, it is important for EuroSIDA to remain in the forefront of investigating the treatment benefits and adverse effects. All study documents, study status, newsletters, scientific publications and presentations are available online and are updated continuously at project website. In general terms, the objective of the EuroSIDA study is to continue a long-term, prospective collection of clinical, laboratory and therapeutic data as well as plasma on a large cohort of consecutive HIV infected patients from across Europe in order to (1) assess the factors associated with the clinical, immunological and virological course of HIV infection and HIV-related co-infections and co-morbidities, and (2) continue to provide and develop a surveillance system to describe temporal changes and regional differences in the clinical course of HIV and HIV-related co-infections and co-morbidities in Europe.

Detailed Description
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Abstract: There are currently over 1½ million people across Europe infected with HIV. The epidemic continues to intensify in the Eastern European region where prevalence of HIV will continue to increase in the years to come. There are significant problems with the management of this public health crisis. Available antiretroviral therapy (ART) - although extremely effective - does not eradicate HIV and hence has to be continued for life. Other limitations are the development of resistance, adverse effects of treatment, and the requirement for strict adherence. Despite these limitations, the widespread use of potent ART has resulted in a dramatic decrease in HIV-related mortality across Europe. As the incidence of AIDS has declined, the relative importance of co-morbidities and co-infections, such as chronic viral hepatitis and tuberculosis (TB), has increased. Around a third of all EuroSIDA patients are co-infected with hepatitis C virus (HCV), and liver-related death is now the second most common cause of death after AIDS. With the introduction of new more potent and better tolerated oral direct acting antivirals (DAAs) against HCV, major changes in the management and outcome HCV co-infection is anticipated in the coming years. However due to the high cost of DAAs, access to new treatment could vary substantially across Europe. Over 23,000 consecutively enrolled HIV-1 positive patients from over 100 clinical centres in 35 European countries, Israel and Argentina - one quarter from the eastern region - are currently enrolled in EuroSIDA. New cohorts of patients are normally enrolled every 2-3 years to ensure all regions of Europe where the epidemic is prevalent are represented so the study will give timely information on the clinical presentation and outcome of European HIV-1 positive patients. In 2012, 2500 additional patients were enrolled into EuroSIDA cohort IX. To be at the forefront of investigating the benefits and adverse effects of new HCV treatment in co-infected patients, the EuroSIDA cohort X enrolled in 2014, consisted of 4000 HIV-1 patients positive for antibodies against HCV. The next cohort to be enrolled (cohort XI) in 2019 will consist of 1500 HIV-1 positive patients. The EuroSIDA study group has now been working on the EuroSIDA study since 1994 and has several notable accomplishments to date, including publication of more than 200 papers in peer-reviewed journals (including the New England Journal of Medicine and the Lancet among others). The focus of EuroSIDA has naturally changed over this period, which demonstrates an eagerness to be flexible, dynamic, and focus on contemporary issues, and the study group is committed to continue working with such principles. In recent years, EuroSIDA has, in addition to the scientific publications, prioritized capacity building in Eastern Europe with HIV seminars, hosting clinicians from Eastern Europe as European AIDS Clinical Society (EACS) students in the office of Copenhagen HIV Programme and sponsoring 2-3 young physicians from Eastern Europe to participate in a statistical course in London every year. Most of the data are collected from the clinics as part of routine care. Additionally, the central plasma repository will be used to extend earlier studies of the viral epidemiology of HIV (resistance and subtypes). Primary study objective: To prospectively study, clinical, therapeutic, demographic, virological and laboratory data from HIV-1 positive persons across Europe in order to determine the long-term virological, immunological and clinical outcome. The specific objectives, falling into four main categories, are as follows: To examine the efficacy of ART and factors that limits this To detect current or emerging late onset adverse events among patients on ART To continue surveillance of HIV in clinics around Europe to describe temporal changes and regional difference To monitor the uptake and outcome of HCV therapy and development of direct acting antivirals and compare differences between EuroSIDA regions Study visits: Enrolment + follow-up Data collection: For all HIV-1 positive patients enrolled and under follow up, laboratory, therapeutic and clinical data on HIV, viral hepatitis and serious non-AIDS clinical events are collected, as well as demographic data and possible data on pregnancy and the HIV status of the newborn baby. The patients are seen within their clinics as required and according to their local physician. EuroSIDA does not involve patient interviews or study visits, the information is collected from patient notes twice a year until 2017 hereafter once a year.

Official Title
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EuroSIDA Prospective Observational Cohort Study on Clinical and Virological Outcome of European Patients Infected With HIV

Conditions
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HIV, Hepatitis B, Hepatitis C, AIDS, Coinfection, Cardiovascular Diseases, Diabetes Mellitus, Acidosis, Lactic, Renal Insufficiency, Fractures, Bone, End Stage Liver Disease, Kidney Failure, Chronic, Proteinuria

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 infected patients regardless of CD4 cell count and ART status Must be positive for antibodies against HCV regardless of HCV-RNA status, fibrosis stage and prior HCV therapy Exclusion Criteria: Patients under 16 years of age Already enrolled in EuroSIDA through earlier cohort Predefined number of patients has been reached

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort I<br>Enrolled from August 1994. Patients to be included were those attending the out-patient clinic for a scheduled visit (i.e. appointment made more than 2 weeks before time of visit). For patients included in the study from 1994-1997, it was requested that the patients had a cluster of differentiation 4 (CD4) count < 500 cells/µL within the last 5 months before inclusion. For all HIV patients enrolled and under follow up, laboratory, therapeutic and clinical data are collected twice annually. Demographic data, date on pregnancy and serological evidence for infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are collected once annually. | |
| Cohort II<br>Enrolled from January 1996. Patients to be included were those attending the out-patient clinic for a scheduled visit (i.e. appointment made more than 2 weeks before time of visit). For patients included in the study from 1994-1997, it was requested that the patients had a cluster of differentiation 4 (CD4) count < 500 cells/µL within the last 5 months before inclusion. For all HIV patients enrolled and under follow up, laboratory, therapeutic and clinical data are collected twice annually. Demographic data, date on pregnancy and serological evidence for infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are collected once annually. | |
| Cohort III<br>Enrolled from February 1997. Patients to be included were those attending the out-patient clinic for a scheduled visit (i.e. appointment made more than 2 weeks before time of visit). For patients included in the study from 1994-1997, it was requested that the patients had a cluster of differentiation 4 (CD4) count < 500 cells/µL within the last 5 months before inclusion. For all HIV patients enrolled and under follow up, laboratory, therapeutic and clinical data are collected twice annually. Demographic data, date on pregnancy and serological evidence for infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are collected once annually. | |
| Cohort IV<br>Enrolled from March 1999. Patients to be included were those attending the out-patient clinic for a scheduled visit (i.e. appointment made more than 2 weeks before time of visit). The eligibility criteria of a cluster of differentiation 4 (CD4) count < 500 cells/µL within the last 5 months before inclusion has been removed for patients joining the study in 1999 and beyond, since the intention of the study is to include most patients eligible for antiretroviral therapy. For all HIV patients enrolled and under follow up, laboratory, therapeutic and clinical data are collected twice annually. Demographic data, date on pregnancy and serological evidence for infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are collected once annually. | |
| Cohort V<br>Patients to be included were those aged 16 years or older attending the out-patient clinic for a scheduled visit (i.e. appointment made more than 2 weeks before time of visit), regardless of cluster of differentiation 4 (CD4) cell count. For all HIV patients enrolled and under follow up, laboratory, therapeutic and clinical data are collected twice annually. Demographic data, date on pregnancy and serological evidence for infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are collected once annually. | |
| Cohort VI<br>Patients to be included were those aged 16 years or older attending the out-patient clinic for a scheduled visit (i.e. appointment made more than 2 weeks before time of visit), regardless of cluster of differentiation 4 (CD4) cell count. For all HIV patients enrolled and under follow up, laboratory, therapeutic and clinical data are collected twice annually. Demographic data, date on pregnancy and serological evidence for infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are collected once annually. | |
| Cohort VII<br>Patients to be included were those aged 16 years or older attending the out-patient clinic for a scheduled visit (i.e. appointment made more than 2 weeks before time of visit), regardless of cluster of differentiation 4 (CD4) cell count. For all HIV patients enrolled and under follow up, laboratory, therapeutic and clinical data are collected twice annually. Demographic data, date on pregnancy and serological evidence for infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are collected once annually. | |
| Cohort VIII<br>Patients to be included were those aged 16 years or older attending the out-patient clinic for a scheduled visit (i.e. appointment made more than 2 weeks before time of visit), regardless of cluster of differentiation 4 (CD4) cell count. For all HIV patients enrolled and under follow up, laboratory, therapeutic and clinical data are collected twice annually. Demographic data, date on pregnancy and serological evidence for infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are collected once annually. | |
| Cohort IX<br>Enrolled from December 2011. Patients to be included were those aged 16 years or older attending the out-patient clinic for a scheduled visit (i.e. appointment made more than 2 weeks before time of visit), regardless of cluster of differentiation 4 (CD4) cell count. For all HIV patients enrolled and under follow up, laboratory, therapeutic and clinical data are collected twice annually. Demographic data, date on pregnancy and serological evidence for infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are collected once annually. | |
| Cohort X<br>All patients should be consecutive patients (except those already enrolled in EuroSIDA), or patients who had a scheduled visit (i.e. those who made an appointment >2 weeks prior to their visit) in the outpatient clinic regardless of cluster of differentiation 4 (CD4) cell count and ART status). Enroll patients of 16 years or older and positive for antibodies against hepatitis C virus (regardless of HCV-RNA status, fibrosis stage and prior treatment against hepatitis C). For all HIV patients enrolled and under follow up, laboratory, therapeutic and clinical data are collected twice annually. Demographic data, date on pregnancy and serological evidence for infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are collected once annually. | |
| Cohort XI<br>HIV-1 positive persons ≥18 years of age, not already enrolled in EuroSIDA, are eligible for inclusion. Participants should be enrolled consecutively in one of the following two groups: Participants who have started integrase inhibitor (INSTI) based antiretroviral therapy (ART) after 1/1/2012 and have a CD4 cell count and HIV-RNA available in the 12 months prior to starting INSTI or within 3 months after starting INSTI If participants have not started INSTI, they should be included providing they have a CD4/HIV-RNA in the 12 months prior to baseline or within 3 months after baseline. For all patients enrolled and under follow up, laboratory, therapeutic, clinical and demographic data, date on pregnancy and data on hepatitis B virus (HBV) and hepatitis C virus (HCV) are collected once annually. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of long-term virological, immunological and morbidity and mortality outcomes across different regions in Europe; and demographic, clinical, therapeutic and viral factors associated with these outcomes | EuroSIDA is a non-interventional epidemiological cohort study that collects structured data. Data is not collected real time, but in 6-monthly intervals. The clinical data is centered on collecting laboratory variables and ascertaining predefined meaningful clinical events as well as reasons for changing and or stopping treatment regimens. The observational cohort study concept means that EuroSIDA does not collect Adverse Events, Adverse Reactions, Serious Adverse Reactions or Suspected Unexpected Serious Adverse Reactions as defined by pharmacovigilance requirements for marketing authorization holders. However, EuroSIDA often analyses and reports specific clinical events of interest, occasionally related to drug classes, but more regularly with a focus on regional differences in treatment and care. | From date of enrollment until the date of progression, lost to follow-up or death, whichever came first, assessed up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients experiencing HIV-related events over time |  | From date of enrollment until the date of progression, lost to follow-up or death, whichever came first, assessed up to 5 years | 
| Number of participants experiencing HIV-related events by region |  | From date of enrollment until the date of progression, lost to follow-up or death, whichever came first, assessed up to 5 years | 
| Proportion of HCV infected patients who start treatment with direct acting antiretrovirals |  | From date of enrollment until the date of progression, lost to follow-up or death, whichever came first, assessed up to 5 years | 
| Rate of sustained virologic response 12 (SVR12) in HCV-infected patients | Share of patients with undetectable viral load 12 weeks after cessation of therapy targeting HCV infection | From date of enrollment until the date of progression, lost to follow-up or death, whichever came first, assessed up to 5 years | 
| Incidence of liver-related clinical outcomes in HCV-infected patients receiving HCV therapy |  | From date of enrollment until the date of progression, lost to follow-up or death, whichever came first, assessed up to 5 years | 
| Incidence of non-liver-related clinical outcomes in HCV-infected patients receiving HCV therapy |  | From date of enrollment until the date of progression, lost to follow-up or death, whichever came first, assessed up to 5 years | 
| Incidence of liver-related clinical outcomes in HCV-infected patients not receiving HCV therapy |  | From date of enrollment until the date of progression, lost to follow-up or death, whichever came first, assessed up to 5 years | 
| Incidence of non-liver-related clinical outcomes in HCV-infected patients not receiving HCV therapy |  | From date of enrollment until the date of progression, lost to follow-up or death, whichever came first, assessed up to 5 years | 
| Incidence of toxicities related to direct acting antivirals by regions |  | From date of enrollment until the date of progression, lost to follow-up or death, whichever came first, assessed up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, HIV-1, Hepatitis C, HCV, prospective, cohort, coinfection