Epidemiological Research Europe Research Articles

Low compliance with hepatocellular carcinoma screening guidelines in hepatitis B/C virus co-infected HIV patients with cirrhosis.

The incidence of hepatocellular carcinoma (HCC) in patients co-infected with HIV and hepatitis B virus (HBV) or hepatitis C virus (HCV) is increasing. In patients with cirrhosis, guidelines recommend HCC screening every 6 months. We assessed compliance with HCC screening guidelines in cirrhotic HBV/HCV-HIV-co-infected patients. HBV/HCV-HIV-co-infected patients with cirrhosis were enrolled from 4 European prospective cohorts participating in the COHERE collaboration, followed from 1 January 2005-1 January 2015. Assessment of liver cirrhosis was based on clinical diagnosis and liver biopsy or Fibroscan. Compliance with HCC screening guidelines was defined as one ultrasound every 6 months. Generalized estimating equation models adjusted for repeated measurements were fitted to determine predictors of low compliance. Different sensitivity analyses were performed and validation of the data was carried out by randomly checking 10% of each cohort's data. 646 HIV-patients with the diagnosis of cirrhosis were included: 518 (80%) HCV-, 85 (13%) HBV- and 43 (7%) HBV/HCV-co-infected. Median age at cirrhosis diagnosis was 44 years, median follow-up time since diagnosis was 5.3 years. Screening </=6 months was performed in 6-18% of individuals from 2005-2015. If the screening interval was increased to 9 or 12 months, compliance improved to 7-24% and 7-30% respectively. Thus, compliance with HCC screening guidelines in cirrhotic HIV-patients co-infected with HBV and/or HCV in Europe is low. In light of an ageing population and the increasing prevalence of liver cirrhosis this situation needs to be addressed urgently. This article is protected by copyright. All rights reserved.

Cervical cancer risk in women living with HIV across four continents: A multicohort study.

We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person-years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382-523), 136 in Latin America (95% CI: 85-219), 76 in North America (95% CI: 48-119) and 66 in Europe (95% CI: 57-77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27-4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73-16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37-1.71). Overall, ICC rates increased with age (>50 years vs. 16-30 years, aHR: 1.57, 95% CI: 1.03-2.40) and lower CD4 cell counts at ART initiation (per 100 cell/μl decrease, aHR: 1.25, 95% CI: 1.15-1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities.

Non-Hodgkin lymphoma risk in adults living with HIV across five continents.

To compare non-Hodgkin lymphoma (NHL) incidence rates in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America. We included cohort data of adults living with HIV who started ART after 1995 within the framework of the International epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). We used flexible parametric survival models to compare regional NHL rates at 2 years after ART start and to identify risk factors for NHL. We included 210 898 adults with 1.1 million person-years (pys) of follow-up and 1552 incident NHL cases (raw overall incidence rate 142/100 000 pys). After adjusting for age at ART start, first-line ART regimen, calendar period of ART start, and especially current CD4 cell count, NHL rates were similar across regions for most population groups. However, South African women remained at increased risk of developing NHL compared with their European counterparts [adjusted hazard ratio [aHR] 1.79, 95% CI 1.19-2.70]. In Europe, Latin, and North America, NHL risk was highest in MSM (aHR 1.30, 95% CI 1.14-1.48), followed by heterosexual men (referent), and women (aHR 0.66, 95% CI 0.57-0.78). The risk of developing NHL is higher in women in South Africa than in Europe and higher in MSM compared with heterosexual men and women. Reasons for these differences remain unclear. Early ART access and regular patient monitoring to avert low CD4 cell counts remain key for NHL prevention.

Global temporal changes in the proportion of children with advanced disease at the start of combination antiretroviral therapy in an era of changing criteria for treatment initiation.

IntroductionThe CD4 cell count and percent at initiation of combination antiretroviral therapy (cART) are measures of advanced HIV disease and thus are important indicators of programme performance for children living with HIV. In particular, World Health Organization (WHO) 2017 guidelines on advanced HIV disease noted that >80% of children aged <5 years started cART with WHO Stage 3 or 4 disease or severe immune suppression. We compared temporal trends in CD4 measures at cART start in children from low‐, middle‐ and high‐income countries, and examined the effect of WHO treatment initiation guidelines on reducing the proportion of children initiating cART with advanced disease.MethodsWe included children aged <16 years from the International Epidemiology Databases to Evaluate acquired immunodeficiency syndrome (AIDS) (IeDEA) Collaboration (Caribbean, Central and South America, Asia‐Pacific, and West, Central, East and Southern Africa), the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE), the North American Pediatric HIV/AIDS Cohort Study (PHACS) and International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 219C study. Severe immunodeficiency was defined using WHO guidelines. We used generalized weighted additive mixed effect models to analyse temporal trends in CD4 measurements and piecewise regression to examine the impact of 2006 and 2010 WHO cART initiation guidelines.ResultsWe included 52,153 children from fourteen low‐, eight lower middle‐, five upper middle‐ and five high‐income countries. From 2004 to 2013, the estimated percentage of children starting cART with severe immunodeficiency declined from 70% to 42% (low‐income), 67% to 64% (lower middle‐income) and 61% to 43% (upper middle‐income countries). In high‐income countries, severe immunodeficiency at cART initiation declined from 45% (1996) to 14% (2012). There were annual decreases in the percentage of children with severe immunodeficiency at cART initiation after the WHO guidelines revisions in 2006 (low‐, lower middle‐ and upper middle‐income countries) and 2010 (all countries).ConclusionsBy 2013, less than half of children initiating cART had severe immunodeficiency worldwide. WHO treatment initiation guidelines have contributed to reducing the proportion of children and adolescents starting cART with advanced disease. However, considerable global inequity remains, in 2013, >40% of children in low‐ and middle‐income countries started cART with severe immunodeficiency compared to <20% in high‐income countries.

Global Trends in CD4 Cell Count at the Start of Antiretroviral Therapy: Collaborative Study of Treatment Programs.

Early initiation of combination antiretroviral therapy (cART), at higher CD4 cell counts, prevents disease progression and reduces sexual transmission of human immunodeficiency virus (HIV). We describe the temporal trends in CD4 cell counts at the start of cART in adults from low-income, lower-middle-income, upper-middle-income, and high-income countries (LICs, LMICs, UMICs, and HICs, respectively). We included HIV-infected individuals aged ≥16 years who started cART between 2002 and 2015 in a clinic participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) or the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). Missing CD4 cell counts at the start of cART were estimated through multiple imputation. Weighted mixed-effect models were used to smooth trends in median CD4 cell counts. A total of 951855 adults from 16 LICs, 11 LMICs, 9 UMICs, and 19 HICs were included. Overall, the modeled median CD4 cell count at the start of cART increased from 2002 to 2015, from 78/µL (95% confidence interval, 58-104/µL) to 287/µL (250-328/µL) in LICs, from 99/µL (71-140/µL) to 234/µL (192-285/µL) in LMICs, from 71/µL (49-104/µL) to 311/µL (255-379/µL) in UMICs, and from 161/µL (143-181/µL) to 327/µL (286-372/µL) in HICs. In LICs, LMICs, and UMICs, the increase was more pronounced in women; in HICs, the opposite was observed. Median CD4 cell counts at the start of cART increased in all income groups, but generally remained below 350/μL in 2015. Substantial additional efforts and resources are required to achieve earlier diagnosis, linkage to care, and initiation of cART.

Is response to anti-hepatitis C virus treatment predictive of mortality in hepatitis C virus/HIV-positive patients?

Long-term clinical outcomes after hepatitis C virus (HCV) treatment of HIV/HCV patients are not well described. We aimed to compare the risk of all-cause and liver-related death (LRD) according to HCV treatment response in HIV/HCV patients in the multicohort study Collaboration of Observational HIV Epidemiological Research in Europe. All patients who had started pegylated interferon + ribavirin (baseline) and followed for at least 72 weeks after baseline were included. Patients were categorized into three response groups depending on treatment duration and HCV-RNA measured in the window 24-72 weeks after baseline. Patients who received at least 24 weeks of therapy were defined as responders if their last HCV-RNA measured between 24 and 72 weeks after baseline was negative, and having 'unknown response' if HCV-RNA was unknown. Nonresponders were treated for less than 24 weeks or were HCV-RNA+ between 24 and 72 weeks after baseline. Mortality rates were compared using survival analysis, and Cox regression was used to compare hazard ratios of death between response groups. A total of 3755 patients were included: 1031 (27.5%) responders, 1639 (43.6%) nonresponders and 1085 (28.9%) with unknown response. Rates [per 1000 person-years of follow-up, 95% confidence interval (CI)] of all-cause death were 17.59 (14.88-20.78), 10.43 (7.62-14.28) and 11.00 (8.54-14.23) for nonresponders, responders and unknown responders, respectively. After adjustment, the relative hazard (nonresponders vs. responders) for all-cause death, LRD and nonliver-related death was 1.53 (95% CI 1.06-2.22), 3.39 (95% CI 1.32-8.75) and 1.22 (95% CI 0.80-1.84), respectively. HIV/HCV patients with a favourable virological response to pegylated interferon + ribavirin had reduced risk of all-cause and LRD, whereas there was no difference in risk of nonliver-related death when comparing responders and nonresponders.

Inequalities by educational level in response to combination antiretroviral treatment and survival in HIV-positive men and women in Europe

Socioeconomic inequality challenges population-level implementation of health interventions. We investigated differences by educational level in clinical, virological, and immunological responses to combined antiretroviral treatment (cART) in HIV-positive men and women in Collaboration of Observational HIV Epidemiological Research in Europe, a European collaboration. Data were pooled from 15 cohorts in eight countries of patients initiating cART in 1996-2013 with data on educational level categorized in UNESCO/ISCED classifications. Kaplan-Meier curves, Cox and piecewise linear mixed models were used. Of 24 069 HIV-positive patients, 9% had not completed primary education, 32% had completed primary, 44% secondary, and 15% tertiary education. Overall, 21% were women, who were overrepresented in lower educational strata. During 132 507 person-years of follow-up, 1081 individuals died; cumulative mortality decreased with higher educational level (P < 0.001). Over 122 765 person-years, new AIDS events or death occurred in 2598 individuals; differences by education were more marked than for death alone (P < 0.001). Virological response was achieved by 67% of patients without completed basic education, 85% with completed primary education, 82% with secondary, and 87% with tertiary (P < 0.001). Patients with higher education had higher CD4 cell count at cART initiation and at each time after cART but rate of CD4 cell count recovery did not differ. Differences in mortality and clinical responses were similar for men and women and were not entirely explained by delayed HIV diagnosis and late cART initiation. HIV-positive patients with lower educational level had worse responses to cART and survival in European countries with universal healthcare. To maximize the population impact of cART, Europe needs to decrease the socioeconomic divide.

Kaposi Sarcoma Risk in HIV-Infected Children and Adolescents on Combination Antiretroviral Therapy From Sub-Saharan Africa, Europe, and Asia.

The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS and the Collaboration of Observational HIV Epidemiological Research in Europe. We included HIV-infected children aged <16 years at cART initiation from 1996 onward. We used Cox models to calculate hazard ratios (HRs), adjusted for region and origin, sex, cART start year, age, and HIV/AIDS stage at cART initiation. We included 24 991 children from eastern Africa, southern Africa, Europe and Asia; 26 developed KS after starting cART. Incidence rates per 100 000 person-years (PYs) were 86 in eastern Africa (95% confidence interval [CI], 55-133), 11 in southern Africa (95% CI, 4-35), and 81 (95% CI, 26-252) in children of sub-Saharan African (SSA) origin in Europe. The KS incidence rates were 0/100 000 PYs in children of non-SSA origin in Europe (95% CI, 0-50) and in Asia (95% CI, 0-27). KS risk was lower in girls than in boys (adjusted HR [aHR], 0.3; 95% CI, .1-.9) and increased with age (10-15 vs 0-4 years; aHR, 3.4; 95% CI, 1.2-10.1) and advanced HIV/AIDS stage (CDC stage C vs A/B; aHR, 2.4; 95% CI, .8-7.3) at cART initiation. HIV-infected children from SSA but not those from other regions, have a high risk of developing KS after cART initiation. Early cART initiation in these children might reduce KS risk.

Association of Job Demands with Work Engagement of Japanese Employees: Comparison of Challenges with Hindrances (J-HOPE)

ObjectivesRecent epidemiological research in Europe has reported that two groups of job demands, i.e., challenges and hindrances, are differently associated with work engagement. The purpose of the present study was to replicate the cross-sectional association of workload and time pressure (as a challenge) and role ambiguity (as a hindrance) with work engagement among Japanese employees.MethodsBetween October 2010 and December 2011, a total of 9,134 employees (7,101 men and 1,673 women) from 12 companies in Japan were surveyed using a self-administered questionnaire comprising the Job Content Questionnaire, National Institute for Occupational Safety and Health Generic Job Stress Questionnaire, short 10-item version of the Effort-Reward Imbalance Questionnaire, short nine-item version of the Utrecht Work Engagement Scale, and demographic characteristics. Multilevel regression analyses with a random intercept model were conducted.ResultsAfter adjusting for demographic characteristics, workload and time pressure showed a positive association with work engagement with a small effect size (standardized coefficient [β] = 0.102, Cohen’s d [d] = 0.240) while role ambiguity showed a negative association with a large effect size (β = −0.429, d = 1.011). After additionally adjusting for job resources (i.e., decision latitude, supervisor support, co-worker support, and extrinsic reward), the effect size of workload and time pressure was not attenuated (β = 0.093, d = 0.234) while that of role ambiguity was attenuated but still medium (β = −0.242, d = 0.609).ConclusionsAmong Japanese employees, challenges such as having higher levels of workload and time pressure may enhance work engagement but hindrances, such as role ambiguity, may reduce it.

Is It Safe to Discontinue PrimaryPneumocystis jiroveciPneumonia Prophylaxis in Patients with Virologically Suppressed HIV Infection and a CD4 Cell Count &lt;200 Cells/μL?

Current guidelines suggest that primary prophylaxis for Pneumocystis jiroveci pneumonia (PcP) can be safely stopped in human immunodeficiency virus (HIV)-infected patients who are receiving combined antiretroviral therapy (cART) and who have a CD4 cell count >200 cells/microL. There are few data regarding the incidence of PcP or safety of stopping prophylaxis in virologically suppressed patients with CD4 cell counts of 101-200 cells/microL. The Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) included data from 23,412 patients from 12 European cohorts who started taking cART after 1997. Poisson regression was used to model incidence rate ratios (IRRs) of primary PcP. There were 253 PcP cases during 107,016 person-years of follow-up (PYFU). Prophylaxis significantly reduced the incidence of PcP among patients with current CD4 cell counts 100 cells/microL (adjusted IRR, 0.41; 95% confidence interval [CI], 0.27-0.60) but not significantly among those with current CD4 cell counts of 101-200 cells/microL (adjusted IRR, 0.63; 95% CI, 0.34-1.17). The incidence of PcP among patients who had a current CD4 cell count of 100-200 cells/microL, who had a viral load <400 copies/mL, and who were receiving prophylaxis was 2.1 cases per 1000 PYFU (95% CI, 0.8-4.3 cases per 1000 PYFU; 7 events occurred during 3363 PYFU), whereas 1.2 cases per 1000 PYFU (95% CI, 0.2-4.5 cases per 1000 PYFU; 2 events occurred during 1614 PYFU) occurred among persons who were not receiving prophylaxis (adjusted IRR, 1.65; 95% CI, 0.33-8.15). Among patients who discontinued PcP prophylaxis after starting cART, the incidence of primary PcP was 0 cases per 1000 PYFU (95% CI, 0.0-2.7 cases per 1000 PYFU; 0 events occurred during 1363 PYFU) for patients who had a current CD4 cell count of 101-200 cells/microL and who were receiving cART. The incidence of primary PcP among patients who had virologically suppressed HIV infection, were receiving cART, and who had CD4 cell counts >100 cells/microL was low irrespective of prophylaxis use. Discontinuation of prophylaxis may be safe in patients with CD4 counts of 101-200 cells/microL and suppressed viral load.

HIV-Related Hodgkin Lymphoma in the Era of Highly Active Antiretroviral Therapy: Incidence and Survival in a Prospective European Multi-Cohort Study On Behalf of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) Study Group.

Abstract 895 Introduction:HIV-infected patients are at increased risk to develop Hodgkin Lymphoma (HL). We examined the incidence and risk factors for HL, and the prognosis of patients with HIV-related HL in the era of highly active antiretroviral therapy (HAART) in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). Patients and Methods:40,168 adult HIV-1 infected patients who started HAART in one of 16 prospective cohort studies in Europe were included in the present analysis. Incidence rates per 100,000 person-years, Kaplan-Meier estimates of cumulative incidence and survival, and adjusted hazard ratios (HRs) from Weibull random-effects models, with 95% confidence intervals (CIs), were calculated. Results:During 159,133 person-years of follow-up, 78 patients were diagnosed with HL. The crude incidence rate of HL was 50.4 per 100,000 person-years for patients who developed HL before starting HAART (17 cases) and 48.7 per 100,000 person-years in patients who were already on HAART (61 cases). Age, gender, CDC clinical stage, CD4 cell counts and HIV-1 RNA viral load at baseline (start of observation) were not significantly associated with the risk of HL. At HL diagnosis median age was 38.9 years (inter quartile range (IQR) 35.3 - 45.9 years) and the median CD4 cell count was 158 cells/μL (IQR 54 – 281 cells/μL). During a median follow-up of 18 months (IQR 4.8 - 34.8 months) 12 of 78 patients with HL died (15%), six of them during the first 6 months after diagnosis. Survival was 88% (95% CI 77% - 94%) at one year and 81% (95% CI 68% - 89%) at two years. Restricting the analysis to patients aged 16-44 years, one year survival in our population (86%, 95% CI 73% - 93%) was less compared to a European population of male Hodgkin patients of similar age (97.7%) [1]. The figure shows Kaplan-Meier plots of cumulative incidence (upper panel) and survival (lower panel). Conclusions:HL incidence rates were similar in HAART treated and untreated patients. In contrast to HIV-related Non-Hodgkin's Lymphoma no clear association with baseline CD4 cell count was observed. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

The ESEMeD-WMH project: strenghtening epidemiological research in Europe through the study of variation in prevalence estimates

The European Study of the Epidemiology of Mental Disorders (ESEMeD) project is the first cross-national European survey to collect data on prevalence, risk factors, health-related quality of life and use of services associated with common mental disorders. Representative samples of the non-institutionalized populations of Belgium, France, Germany, Italy, the Netherlands and Spain were interviewed using the CIDI 3.0, totaling 21,425 adult individuals. There was important variation across countries in prevalence estimates of the disorders studied, with Belgium and France in the highest proportions and Italy and Spain the lowest. Comorbidity of mood and anxiety disorders was frequent in all countries. Use of services due to mental health is low in all European countries, but especially low in Italy. Remarkably, only about one in five participants with a mental disorder had consulted the health services in the prior year. We discuss about the possible explanations of cross-national differences in prevalence estimates of mental disorders, and some of the limitations of the data on alcohol abuse and dependence gathered in the study. We conclude that despite the advances in knowledge about determinants and treatment methods, the care of the mentally ill is rather limited in Europe.