The role of HIV/hepatitis B virus/hepatitis C virus RNA+ triple infection in end-stage liver disease and all-cause mortality in Europe.

BACKGROUND: There are limited data on end-stage liver disease (ESLD) and mortality in people with HIV (PWH) coinfected with both hepatitis B virus (HBV) and hepatitis C virus (HCV). METHODS: All PWH aged greater than 18 under follow-up in EuroSIDA positive for HBsAg (HBV), and/or HCVRNA+, were followed from baseline (latest of 1 January 2001, EuroSIDA recruitment, known HBV/HCV status) to ESLD, death, last visit, or 31 December 2020. Follow-up while HCVRNA- was excluded. In two separate models, Poisson regression compared three groups updated over time; HIV/HBV, HIV/HCV, and HIV/HBV/HCV. RESULTS: Among 5733 included individuals, 4476 (78.1%) had HIV/HCV, 953 (16.6%) had HIV/HBV and 304 (5.3%) had HIV/HBV/HCV. In total, 289 (5%) developed ESLD during 34 178 person-years of follow-up (PYFU), incidence 8.5/1000 PYFU [95% confidence interval (CI) 7.5-9.4] and 707 deaths occurred during 34671 PYFU (incidence 20.4/1000 PYFU; 95% CI 18.9-21.9). After adjustment, compared with those with HIV/HCV, persons with HIV/HBV had significantly lower rates of ESLD [adjusted incidence rate ratio (aIRR) 0.53; 95% CI 0.34-0.81]. Those with HIV/HBV/HCV had marginally significantly higher rates of ESLD (aIRR 1.49; 95% CI 0.98-2.26). Those under follow-up in 2014 or later had significantly lower rates of ESLD compared with 2007-2013 (aIRR 0.65; 95% CI 0.47-0.89). Differences in ESLD between the three groups were most pronounced in those aged at least 40. After adjustment, there were no significant differences in all-cause mortality across the three groups. CONCLUSION: HIV/HBV-coinfected individuals had lower rates of ESLD and HIV/HBV/HCV had higher rates of ESLD compared with those with HIV/HCV, especially in those aged more than 40. ESLD decreased over time across all groups. CLINICALTRIALSGOV IDENTIFIER: NCT02699736.

Variation in antiretroviral treatment coverage and virological suppression among three HIV key populations.

OBJECTIVES: We assessed differences in antiretroviral treatment (ART) coverage and virological suppression across three HIV key populations, as defined by self-reported HIV transmission category: sex between men, injection drug use (IDU) and heterosexual transmission. DESIGN: A multinational cohort study. METHODS: Within the EuroSIDA study, we assessed region-specific percentages of ART-coverage among those in care and virological suppression (<500 copies/ml) among those on ART, and analysed differences between transmission categories using logistic regression. RESULTS: Among 12 872 participants followed from 1 July 2014 to 30 June 2016, the percentages of ART-coverage and virological suppression varied between transmission categories, depending on geographical region (global P for interaction: P = 0.0148 for ART-coverage, P = 0.0006 for virological suppression). In Western [adjusted odds ratio (aOR) 1.41 (95% confidence interval 1.14-1.75)] and Northern Europe [aOR 1.68 (95% confidence interval 1.25-2.26)], heterosexuals were more likely to receive ART than MSM, while in Eastern Europe, there was some evidence that infection through IDU [aOR 0.60 (95% confidence interval 0.31-1.14)] or heterosexual contact [aOR 0.58 (95% confidence interval 0.30-1.10)] was associated with lower odds of receiving ART. In terms of virological suppression, people infected through IDU or heterosexual contact in East Central and Eastern Europe were around half as likely as MSM to have a suppressed viral load on ART, while we observed no differences in virological suppression across transmission categories in Western and Northern Europe. CONCLUSION: In our cohort, patterns of ART-coverage and virological suppression among key populations varied by geographical region, emphasizing the importance of tailoring HIV programmes to the local epidemic.

A Population-Based Surveillance Study on the Epidemiology of Hepatitis C in Estonia.

Background and objective: The hepatitis C virus (HCV)-infected patients serve as a reservoir for transmission of the disease to others and are at risk of developing chronic hepatitis C, cirrhosis, and hepatocellular carcinoma. Although the epidemiological data of high rate HCV infection have been obtained in many countries, such data are insufficient in Estonia. Therefore, the aim of the study was to analyze country-specific data on HCV patients. Materials and methods: Data about age, gender, diagnosis, possible risk factors, coinfections, HCV genotypes, liver fibrosis stages and extrahepatic manifestations were collected from 518 patients. Results: The most common risk factors for hepatitis C were injection drug use and tattooing in the 30⁻39 and 40⁻49 year age groups, and blood transfusion in the 50⁻59 and 60⁻69 year age groups. The other risk factors established were profession-related factors and sexual contact. The prevailing viral genotype among the HCV infected patients was genotype 1 (69% of the patients) followed by genotype 3 (25%). Genotypes 1 and 3 correlated with blood transfusions before 1994, drug injections and tattooing. Conclusions: Our study provides the best representation of genotype distribution across Estonia. As a result of the study, valuable data has been collected on hepatitis C patients in Estonia.

Aging and the evolution of comorbidities among HIV-positive individuals in a European cohort.

OBJECTIVES: To describe changes in the prevalence of comorbidities and risk factors among HIV-positive individuals in the EuroSIDA study. DESIGN: Comparison of two cross-sectional cohorts of HIV-positive adults under active follow-up in 2006 and 2014. METHODS: Baseline demographics and prevalence of comorbidities were described. Factors associated with the prevalence of chronic kidney disease (CKD) and cardiovascular disease (CVD) were assessed by logistic regression modelling using generalized estimating equations. RESULTS: Nine thousand, seven hundred and ninety-eight individuals were under active follow-up in EuroSIDA during 2006 and 12 882 during 2014. Compared with study participants in 2006, those in 2014 were older [median age 48.6 years (IQR 40.3-55.1) vs. 43.1 years (37.2-50.0) in 2006] and had higher prevalence of hypertension (59.6 vs. 47% in 2006), diabetes (6.3 vs. 5.4%), CKD (6.9 vs. 4.1%) and CVD (5.0 vs. 3.7%). Individuals in the 2014 cohort had higher odds for CKD (unadjusted OR 2.62, 95% CI 2.30-2.99, P < 0.0001) and CVD (OR 1.88, CI 1.68-2.10, P < 0.0001), but after multivariable adjustment for age group, comorbidities and other factors, year of cohort was no longer significantly associated with the odds of CKD [adjusted OR (aOR) 0.97, CI 0.52-1.82, P = 0.92) or of CVD (aOR 0.94, CI 0.54-1.63, P = 0.82). CONCLUSION: Between 2006 and 2014, the population aged and experienced an overall higher prevalence of non-AIDS comorbidities, including CKD and CVD. The increase in CVD could be explained by the aging population, and the increase in CKD by aging and changes in other factors. Treatment strategies balancing HIV outcomes with long-term management of comorbidities remain a priority.

Uptake of tenofovir-based antiretroviral therapy among HIV-HBV-coinfected patients in the EuroSIDA study.

BACKGROUND: According to guidelines all HIV-HBV-coinfected patients should receive tenofovir-based combination antiretroviral therapy (cART). We aimed to investigate uptake and outcomes of tenofovir-based cART among HIV-HBV patients in the EuroSIDA study. METHODS: All hepatitis B surface antigen (HBsAg)+ patients followed up after 1 March 2002 were included. Changes in the proportion taking tenofovir-based cART over time were described. Poisson regression was used to investigate the relationship between tenofovir use and clinical events. RESULTS: 953 HIV-HBV patients were included. Median age was 41 years and patients were predominantly male (85%), White (82%) and ART-experienced (88%). 697 and 256 were from Western and Eastern Europe, respectively. 55 started cART during follow-up, the proportion starting with CD4+ T-cell count <350 cells/mm3 decreased from 85% to 52% in the periods 2002-2006 to 2007-2015. Tenofovir use, among those taking cART, increased from 4% in 2002 to 73% in 2015. Compared to West, tenofovir use was lower in East in 2005 (7% versus 42%), and remained lower in 2015 (63% versus 76%). Among 602 patients taking tenofovir-based cART during follow-up, 155 (26%) discontinued tenofovir. 27 of all discontinuations were due to adverse effects. Only 14 started entecavir and/or adefovir after tenofovir discontinuation, whereas 10 started pegylated interferon. Tenofovir use was not significantly associated with lower risk of liver-related clinical events (n=51), adjusted incidence rate ratio (IRR) 0.64 (95% CI 0.35, 1.18) for comparing patients on tenofovir with those off tenofovir. CONCLUSIONS: Although use of tenofovir-based cART among HIV-HBV patients has increased across Europe, a substantial proportion are still starting cART late and are receiving suboptimal HBV therapy.

Antiretroviral therapy (ART) adherence and correlates to nonadherence among people on ART in Estonia.

There are little data on antiretroviral therapy (ART) adherence among patients in Eastern Europe, despite the high incidence of HIV infection and the growing number of HIV-infected individuals who are being prescribed ART. The aim of this study was to measure rates of adherence to ART and factors associated with nonadherence among patients receiving care at an outpatient HIV clinic in Estonia. The study was based on cross-sectional data from a convenience sample of 144 patients receiving outpatient HIV care. Data were obtained via interviewer-administered surveys and data abstraction from clinical records. Adherence was measured from a 3-day patient self-report. Among 144 participants (mean age 33.8 years), two-thirds (63%) had been infected with HIV through intravenous drug use. Most (74%) were co-infected with hepatitis C (HCV). Perfect adherence over the last 3 days was commonly reported (88% [95% CI 81-92%]) with nonperfect adherence associated with greater concerns about the potential adverse consequences of taking ART (adjusted odds ratio [AOR] 4.8, 95% CI 1.2-34.0) and average (versus good/very good) self-reported health status (AOR 4.7, 95% CI 1.2-31.4). Self-reported ART adherence in this sample of Estonian HIV-positive patients in clinical care was similar to rates observed in Western Europe and other developed countries. Results suggest that adherence education and support may be most helpful if they specifically target the development of positive beliefs, reduction of negative expectancies towards ART.