Cohort Profile: PISCIS, a population-based cohort of people living with HIV in Catalonia and Balearic Islands

Abstract

The PISCIS Cohort is a prospective, population-based, longitudinal study of people living with HIV (PLWH) in Catalonia and the Balearic Islands (Spain), active since 1998 and with a coverage of HIV-diagnosed patients of 82% and 60%, respectively. In Catalonia, the PISCIS Cohort is part of the formal, longitudinal, public health surveillance system and can be anonymously linked to other strategic sources of programmatic data for research purposes. As of December 2020, 28 017 PLWH were enrolled in the cohort (273 488 person-years of follow-up), of whom 3948 died and 5715 were lost to follow-up (LTFU). The cohort is largely male (80.9%), the main route of HIV transmission was through sex between men (43.9%), and migrants (non-Spanish origin) contribute 28.8%. Out of all PLWH, 7020 (25.1%) had AIDS at cohort inclusion and 5961 (21.3%) developed AIDS during follow-up. Data are solicited from 17 participating centres annually. Patients’ visits are between every 6 and 12 months. Sociodemographic, clinical, laboratory and antiretroviral treatment (ART) data are collected longitudinally, and treatment prescriptions are extracted for the Catalan Healthcare System database. PISCIS has collaborated or continues to collaborate in international cohort consortia such as COHERE, HIV-Causal, ART-CC and RESPOND. Dataset for specific research questions and analysis is available to the scientific community upon formal request. Further information can be found at [www.pisciscohort.org] or by contacting [[email protected]]. The PISCIS Cohort was initiated in 1998 with the aims of enhancing formal HIV surveillance and facilitating clinical-epidemiological applied research by means of standardizing programmatic data collection and management from HIV units in participating hospitals in Catalonia and Balearic Islands, Spain. In Catalonia, the cohort is formally recognized as part of the longitudinal public health surveillance (under the Decree 203/2015 of 15 September 15, 20151) and is part of the Catalan AIDS/HIV/sexually transmitted infections (STI) Integrated Surveillance System (SIVES).2 The PISCIS cohort is coordinated and managed by the Centre for Epidemiological Studies of Sexually Transmitted Infections and HIV/AIDS in Catalonia (CEEISCAT) as the responsible unit of HIV/STI surveillance and monitoring and evaluation of these infections for the Catalan Health Department. Moreover, the PISCIS cohort has received support through specific research project grants from different agencies, including the Foundation for Innovation and Prospective Health in Spain (FIPSE), Health Research Fund (FIS), Fundació La Marató de TV3, Obra Social La Caixa and funds received from international collaborations such as RESPOND, HIV-CAUSAL, ART-CC and COHERE. Finally, it depends on the voluntary dedication of clinicians and research coordinators in the participating hospitals who support the sending and maintenance of data. Therefore, the PISCIS Cohort is a national strategic information source, with the current objective of carrying out clinical-epidemiological and longitudinal surveillance of patients diagnosed with HIV, optimizing the comprehensive management of people living with HIV (PLWH) and answering clinical and epidemiological questions through nested research projects. Over the years, the PISCIS Cohort has increased its coverage from 51% of all PLWH in Catalonia in 1998 to 82% in 2020 (the coverage of the Balearics will increase after the 2021 data collection), has been linked with several other strategic information systems like the Spanish Mortality Registry (Índice Nacional de Defunciones—INDEF) and Public Data Analysis Program for Health Research and Innovation (PADRIS) and has been part of several international initiatives and cohort consortia such as COHERE, ART-Consortium Collaboration, HIV-Causal and RESPOND. To adapt to the changing patterns and necessities of PLWH, in recent years we have fostered new studies and analyses embedded within the original cohort. Among them, PISCIS has implemented the Vive+ project which describes the health-related quality of life (HRQoL) of PLWH and identifies potential HRQoL determinants among the PISCIS population, as well as satisfaction with the current health system, within a gender perspective.3 Moreover, other studies are addressing aging and the burden of multimorbidity patterns and polypharmacy in PLWH over 60 years.4 Because of the importance of patient attrition to meeting the Sustainable Development Goal (SDG-3) of ending the HIV/AIDS epidemic by 2030, PISCIS, with a retention rate of 85%5, has also been committed to identifying determinants for attrition among PLWH lost to follow-up and to pilot strategies to re-engage them to care. Last, the potential impact of SARS-CoV-2 on PLWH has been a crucial area of research within the cohort during the past 2 years.6 The PISCIS cohort study has conducted studies to understand the differences in clinical outcomes between the general population and among PLWH7 and contributed to valuable knowledge regarding the sociodemographic, clinical and immunological factors associated with SARS-CoV-2 infection and severe COVID-19 outcomes among PLWH.8 Additionally, the cohort is currently working actively to bring clarity to other matters, including the impact of ART on outcomes, benefits of COVID-19 vaccines in this population and long-term implications of COVID-19. The PISCIS Cohort is an open, population-based, longitudinal, systematic, prospective and multicentric HIV cohort study, ongoing since 1998, of PLWH in care in Catalonia and the Balearic Islands, Spain. In 1998, prior to the commencement of the cohort study, an invitation to participate was sent to the Regional Catalan Hospitals network that belonged to the HIV/AIDS Working Group in Spain and subsequently to all other regional hospitals in Catalonia and the Balearic Islands, as well as HIV units of hospitals in the Madrid, Seville and San Sebastian. Hospitals that initially agreed to participate were sent a questionnaire to evaluate their data collection systems and hardware availability. By the end, only 10 hospitals in Catalonia and one from the Balearic Islands were included through the implementation of a three-phase plan: the creation and distribution of patient data management software, the validation of the software through the collection of retrospective data between 1998 and 2000, and prospective data collection henceforth. Between 2000 and 2016, five other centres from Catalonia and one from the Balearic Islands were incorporated, providing retrospective data of participants meeting the inclusion criteria. Currently, the cohort annually collects data on all PLWH aged ≥16 years with a first visit after 1 January 1998 at any of the 17 participating HIV hospital outpatient clinics. Although not all hospitals in the region are included, those contained within the cohort cover approximately 82% of all PLWH in Catalonia and an estimated 60% of those in the Balearic Islands. All patients who meet the inclusion criteria and are visited in one of the Catalan hospitals’ outpatient clinics are included in the cohort, as per Decree 203/2015 (article 3.3.3).1 Patients can request the Catalan Department of Health to remove their personal and clinical information from the government health database. Patients from the Balearic Islands are asked to participate, sign a consent form if they agree and can request to be excluded at any time upon request. As of December 2020, 28 017 PLWH had been enrolled into the cohort, contributing to 273 488 person-years of follow-up. Baseline information of the PISCIS cohort is presented in Table 1. The PISCIS population is 80.9% male (n = 22 653), 28.8% migrants (n = 8059) and median age of the cohort at enrolment 35.4 years (Table 1). Out of all participants at cohort enrolment, 67.7% (n = 18 972) were naive to ART and 52.7% (n = 14 133) of those with valid CD4 count (n = 26 818) were late presenters (persons with CD4 <350 cells/mm3 or AIDS-defining illness), of whom 65.4% (n = 9244) had advanced HIV disease (CD4 <200 cells/mm3 or AIDS-defining illness). In terms of mode of transmission groups, men who have sex with men (MSM) represented the largest proportion (54.3%, n = 12 303) among men and infection through sexual contact was the most common transmission route among women (67.2%, n = 3604). Among all participants, the mode of transmission among people who inject drugs (PWID) was 18% (n = 5034). At enrolment, 1.5% (n = 430) of patients had an active hepatitis C virus (HCV) co-infection and 10.3% (n = 2873) had been previously infected. Median CD4 count at entry was 361 cells/mm3 and median plasma HIV viral load was 24 811 copies/mL at cohort entry. In the most recent laboratory results of the patients currently in follow-up, 91.7% of participants presented with undetectable viral loads defined as values below 50 copies/mL. Characteristics of people with HIV included in the PISCIS cohort 1998–2020 IQR, interquartile range; HCV, hepatitis C virus; HBV, hepatitis B virus; NRTI, nucleoside reverse transcriptase inhibitors; NNRTI, non-nucleoside reverse transcriptase inhibitors; PI, protease inhibitors; INSTI, integrase strand transfer inhibitor; ART, antiretroviral treatment. For difference between men and women. At enrolment: time when participant was first visited at a participating centre and so was enrolled in the cohort. CD4 <200 cells/mm3 or AIDS-defining illness. CD4 <350 cells/mm3. PISCIS collects patient-level information of all participants annually from collaborating hospital HIV units. Hospital units continuously collect participants’ information as they attend clinical visits, and at the beginning of every year individual patient data are sent by the technicians or clinicians of each participating centre to CEEISCAT, where the PISCIS coordinating unit is located. Each hospital uses its own data management software, so when all data are collected at the coordinating centre, it first undergoes standardization and harmonization into one common data model, to later undergo quality control and statistical analyses. As errors in the crude data might be corrected by each centre retrospectively, all data since the start of the cohort follow-up are collected every year. All patient data received are effectively anonymized and de-identified, complying with Article 89 of the European Union General Data Protection Regulation (GDPR),9 so that the individuals cannot be identified. Since 2020, PISCIS data have been anonymously linked to the Public Data Analysis Program for Health Research and Innovation (PADRIS),10 an administrative electronic repository which accesses all health records of any individual seen through the Catalan Health System, therefore providing data on primary care visits and emergency unit and hospital admissions, as well as laboratory tests and pharmacy dispensation data. In the PISCIS Cohort, lost to follow-up (LTFU) is defined as not having a clinical visit, laboratory test or treatment within the past year before the closing collection date from the corresponding hospital. Patients with new data after being previously considered LTFU are deemed back in follow-up. It is either reported by the centres or assigned when patients met the set criteria. Furthermore, patients lost to follow-up are cross-referenced with the INDEF to find out if they have died somewhere outside the PISCIS’s scope. LTFU show a rise since 2008 with a sharp increase in the year 2020 due to the COVID-19 pandemic. Mortality is confirmed through the INDEF and has been stable between 1998 and 2020 (Figure 1). This cross-reference was done by the clinicians at each participating centre, and as the requested information was of deceased patients, no consent was required. Number of participants enrolled, lost to follow-up and deceased in each year in the PISCIS cohort, stratified by sex, 1998–2020 As of 31 December 2020, 3948 (14.1%) patients had died and 5715 (20.4%) patients were LTFU. LTFU patients were enrolled at an earlier stage in the epidemic and were more likely to be PWID or of non-Spanish origin when compared with those patients currently still in follow-up (Table 2). Characteristics of participants in follow-up, lost to follow-up and deceased in the PISCIS cohort, 1998–2020 IQR, interquartile range; HCV, hepatitis C virus; HBV, hepatitis B virus; NRTI, nucleoside reverse transcriptase inhibitors; NNRTI, non-nucleoside reverse transcriptase inhibitors; PI, protease inhibitors; INSTI, integrase strand transfer inhibitor; ARV, antiretrovirus; ART, antiretroviral treatment. For difference between status groups. At enrolment: time when participant was first visited at a participating centre and so was enrolled in the cohort. CD4 <200 cells/mm3 or AIDS-defining illness. CD4 <350 cells/mm3. Missing or incongruent data are evaluated through quality control reports sent to each hospital centre, so appropriate corrections can be made. Data received each year include all retrospective data since the beginning of the cohort, so any modifications will be included in future data packages. Missing data needed for certain projects were collected by way of an online form created by the coordinating centre and accessible by each clinician exclusively for their patients. Duplicate patient registries were cross-referenced with each other through the patient registry within the Catalan Epidemiological Repository (REC) of the Catalan Department of Health, where all patients are categorized with a single identifiable number. In the PISCIS cohort, data have been harmonized according to a standardized protocol. Baseline sociodemographic (date of birth, gender and country of birth), socioeconomic (employment situation, level of education and country of residence), epidemiological (transmission group, date of first HIV-positive serology, date of last HIV-negative serology and previous antiretroviral treatment), clinical (AIDS-defining and related diseases, CD4 and CD8 lymphocyte count and percentage, plasma HIV viral load, hepatitis B virus (HBV), hepatitis C virus (HCV), Toxoplasma gondii, cytomegalovirus and syphilis serology, tuberculin skin reactivity, and pharmacological treatment data [antiretroviral treatment (ART), chemoprophylaxis of opportunistic infections, adverse effects of ART, and antiretroviral resistance test] are reported. At each follow-up visit, the following variables were reported: opportunistic infections, co-infection with sexually transmitted infections (STIs), HBV and HCV serology (when clinically indicated), and HBV and pneumococcal vaccination data. Laboratory analysis (all of which pertain to the standard of care for an HIV-positive patient) were collected at first and at each follow-up visit. Any results related to CD4 and CD8 cell counts and plasma viral load are reported. Data from the Catalan Health System central database outside the sphere of the HIV clinical unit were extracted to supplement PISCIS, such as visits to other hospital units, primary care centres and emergency care, registered as a 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) code. Pharmacy information is also obtained by way of the Anatomical Therapeutic Chemical (ATC) Classification System (ATC) codes from the World Health Organization (WHO). Hospital and primary care diagnosis and procedures, as well as drug prescriptions, are crucial for ongoing studies on the burden of comorbidities and polypharmacy in this population. This data source has also contributed vitally to studies conducted to assess the impact of COVID-19 in the population and factors associated with severe outcomes. Data on health-related quality of life, sexual behaviours, smoking, alcohol and drug use, perception of stigma and satisfaction with the current health system have been obtained from an opportunistic sample from the cohort, through autocompleted electronic surveys in relation to the Vive+ subproject. All 17 PISCIS centres participated in the project and included 1060 participants, proportionally distributed among the different centres depending on their overall number of PISCIS individuals. Vive+ is planned to be repeated every 3 to 5 years. As part of CEEISCAT, the PISCIS cohort plays a strategic role within the surveillance systems of Catalonia, contributing to the understanding of the HIV epidemic and its clinical management in Catalonia by collecting robust regional data from HIV-positive persons in care11,12 for publications within the Catalan Health Department. PISCIS has a strong focus on public health and identifying trends in vulnerable populations13,14 as well as the general PLWH.15–19 The cohort data have also helped to estimate the HIV continuum of care in Catalonia,5,14 showing that 91% of PLWH is diagnosed, 85% is in clinical follow-up, 82% is receiving ART and 75% of all PLWH has achieved viral suppression in 2020. This indicates that Catalonia achieves all the 90–90–90 objectives, over the European and North American average20 (Figure 2). HIV testing and treatment cascade in Catalonia, 2020 During the past 20 years, the PISCIS Study Group has made substantial clinical to the of in we that late HIV-diagnosed individuals with an of CD4 2 years after had no of individuals In relation to the quality of life in PLWH, the Vive+ was in In this study, out of the 1060 people men and (n = that they were in (n = and (n = the (n = reported having general health and (n = having The that health that or were women people people 60 years of age or and people through drug from the studies are currently Data from the PISCIS were crucial to that during the first year of the COVID-19 in Catalonia, PLWH for had a test care unit and and COVID-19 compared with the general HIV-negative analyses that PLWH with suppression (CD4 <200 HIV and and people aged be at increased of severe Since its PISCIS has contributed data to international HIV cohort consortia collaborating in or research in HIV treatment ART and patient and AIDS-defining and immunological and and HIV drug resistance and All publications can be found at PISCIS has been implemented in different Spanish and therefore collects information corresponding to formal health with a population, facilitating and more the cohort, the to be population with a of PLWH in ART from the Catalan Health System it is estimated that the hospital centres participating in PISCIS cover over 82% of PLWH in treatment living in In the Balearic Islands, currently 60% of the population is are being made in the data and it is that all PLWH from the Balearic Islands will be included by the of Further of this cohort are a and to with new study and control data quality in a and an coordinating centre, clinicians from administrative and data management as HIV patients attend follow-up clinical visits to ART, participants are lost in follow-up patients which is in a cohort PISCIS has a in participating with the main international cohort collaborations like COHERE, and RESPOND, facilitating HIV research where single cohort might not be to is that PISCIS is a of HIV units within 17 different hospitals with different administrative systems and of different patient data management This and in data management and quality control as each will a different data treatment. not all hospitals can the due to the or and this can to in the rate of other variables such as and are to due to time in clinical PISCIS coordinating centre with each unit to these through a quality control and to data from the hospitals’ registries to data Additionally, as the coordinating centre the regional Health patient data from registries are available to be linked with PISCIS a of data and quality and individual data entry time for The PISCIS Study Group with the coordinating (CEEISCAT) research the PISCIS from all centres can to with the cohort which will be subsequently evaluated by the PISCIS January for international will be also available upon request according to the criteria. and can be sent to [[email and information can be found at PISCIS Cohort Group of Data and Data management and statistical of and Diseases Research of Hospital de AIDS and Diseases de of Diseases Research Diseases Hospital de AIDS and Diseases de Hospital de Hospital of de Health de Hospital of de Hospital in General Data support and statistical analysis in de Hospital and Health Health and Foundation de General de AIDS and Diseases of de Hospital in Health de Hospital in General of the of The PISCIS cohort is by the of the coordinating centre Additionally, the cohort has been into the Catalan Epidemiological Surveillance the Decree 203/2015 (article it a strategic source of HIV surveillance in the All participating patients outside Catalonia and not by this have consent The of the included in the study is in with of the Regulation of the European and of the of on the of persons with to the of personal data and on the of such data and the national on Protection of Data of Data Protection of the and developed the of the and out the the and from and All and the of the The PISCIS cohort has received support through the of Public Health of the Catalan Health Department as well as specific research project grants from different research including the Foundation for Innovation and Prospective Health in Spain (FIPSE), Health Research Fund (FIS), Fundació La Marató de TV3, Obra Social La and funds received from international collaborations such as RESPOND, HIV-CAUSAL, ART-CC and COHERE. The like to the and Program of the Catalan Public Health de the Public Data Analysis Program for Health Research and Catalan Health Department and all from the PISCIS Study Group hospitals participants as well as all patients who to their received a personal research during from de Madrid, Spain and a personal research from the Spain during has received research grants from and outside the has received for from and as well as research from and

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