Participation, retention and uptake in a multicentre pre-exposure prophylaxis cohort using online, smartphone-compatible data collection.

OBJECTIVES: The aim of the study was to assess the feasibility of a national pre-exposure prophylaxis (PrEP) programme using smartphone-compatible data collection. METHODS: This was a multicentre cohort study (NCT03893188) enrolling individuals interested in PrEP in Switzerland. All centres participate in the SwissPrEPared programme, which uses smartphone-compatible data collection. Feasibility was assessed after centres had enrolled at least one participant. Participants were HIV-negative individuals presenting for PrEP counselling. Outcomes were participation (number enrolled/number eligible), enrolment rates (number enrolled per month), retention at first follow-up (number with first follow-up/number enrolled), and uptake (proportion attending first visit as scheduled). Participant characteristics were compared between those retained after baseline assessment and those who dropped out. RESULTS: Between April 2019 and January 2020, 987 individuals were assessed for eligibility, of whom 969 were enrolled (participation: 98.2%). The median enrolment rate was 86 per month [interquartile range (IQR) 52-137]. Retention at first follow-up and uptake were both 80.7% (782/969 and 532/659, respectively). At enrolment, the median age was 40 (IQR 33-47) years, 95% were men who have sex with men, 47% had a university degree, and 75.5% were already taking PrEP. Most reported multiple casual partners (89.2%), previous sexually transmitted infections (74%) and sexualized drug use (73.1%). At baseline, 25.5% tested positive for either syphilis, gonorrhoea or chlamydia. Participants who dropped out were at lower risk of HIV infection than those retained after baseline assessment. CONCLUSIONS: In a national PrEP programme using smartphone-compatible data collection, participation, retention and uptake were high. Participants retained after baseline assessment were at considerable risk of HIV infection. Younger, less educated individuals were underrepresented in the SwissPrEPared cohort.

Trends in hepatitis C-related mortality in Switzerland.

In order to accurately assess the burden of hepatitis C (HCV) and develop effective interventions, we must understand the magnitude and trends of mortality related to the disease. In the United States, HCV-related mortality is continuously increasing. We have no comparable data for Switzerland and other European countries, although a modelling study predicted a similar increase. We analysed time trends (1 January 1995-31 December 2014) in HCV-specific mortality rates in the Swiss general population using the death registry of the Swiss Federal Statistical Office (SFSO). We compared HCV-related mortality to HIV-related and hepatitis B (HBV)-related mortality. To determine potential under-reporting in HCV-related mortality, we probabilistically linked the SFSO data to persons who died in the Swiss Hepatitis C Cohort Study (SCCS). SFSO data showed that HCV-related mortality more than doubled between 1995 and 2003, but has since stabilized at ~2.5/100 000 person-years. Since 2000, HCV-related mortality has been higher than HIV-related mortality and was about fivefold higher in 2014. HBV-related mortality remained low at ~0.5/100 000 person-years. Of 4556 persons in the SCCS, 421 have died and 86.2% could be linked to the death registry. According to the SCCS, 133 deaths were HCV-related. HCV was not mentioned on the SFSO death certificate of 45% of these (n = 60/133). In conclusion, HCV-related mortality remained constant, possibly because quality of care was high, or because of under-reporting or because mortality has not yet increased. However, HCV-related mortality is now much higher than HIV- and HBV-related mortality, and under-reporting was common.

Historical epidemiology of hepatitis C virus (HCV) in selected countries.

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Strategies to manage hepatitis C virus (HCV) disease burden.

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm.

The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.

Accessing Hepatitis C patients who are difficult to reach: it is time to overcome barriers.

With the arrival of simple, efficient and safe interferon-free treatment regimens, hepatitis C virus (HCV) therapy will have the potential to be successfully used for the majority of infected patients and prevent the associated morbidity and mortality. With the current treatment uptake rates, only a very small proportion of HCV-infected patients are reached. Paradoxically, treatment rates are lowest in the most affected at-risk group - people who inject drugs (PWID) - which is the major driving force behind the spread of HCV infection. To conquer the increasing problem of HCV-related liver disease, many existing but modifiable obstacles, which prevent detection, assessment and treatment uptake, have to be overcome in this population. This review article summarizes the existing literature on the most relevant barriers preventing HCV care and describes measures to overcome these obstacles.

Treatment outcome in relation to alcohol consumption during hepatitis C therapy: an analysis of the Swiss Hepatitis C Cohort Study.

BACKGROUND: Adherence to hepatitis C treatment is influenced by alcohol as is the action of interferon; yet the clinical significance of the latter remains unclear. The aim of our study was to investigate the influence of ongoing alcohol intake on sustained viral response (SVR) rates in adherent patients receiving hepatitis C treatment. METHODS: A retrospective analysis of patients treated with antiviral therapy for hepatitis C infection who were enrolled in the Swiss Hepatitis C Cohort Study was completed. Patients were eligible for the study if they had their HCV RNA tested 6 months following treatment completion and at least one cohort follow-up visit during HCV therapy, documenting the consumed amount of alcohol. They were assigned to three groups according to the amount of alcohol consumption: group A without alcohol consumption, group B < or =24 g/d alcohol and group C >24 g/d alcohol. RESULTS: 554 patients were included. Patients with at least 80% of the scheduled cumulative dose and duration did not significantly differ between the three groups. SVR rates according to alcohol consumption were 60% for non-drinkers (group A), 57% in group B and 50% in group C. No significant negative influence from alcohol consumption during therapy was observed in the multiple regression analysis for treatment success. CONCLUSION: In this evaluation, we demonstrated comparable SVR rates in non-drinkers and in patients with daily amounts of alcohol intake up to 24 g during hepatitis C therapy.

Active intravenous drug use during chronic hepatitis C therapy does not reduce sustained virological response rates in adherent patients.

SUMMARY: Reluctance has been expressed about treating chronic hepatitis C in active intravenous (IV) drug users (IDUs), and this is found in both international guidelines and routine clinical practice. However, the medical literature provides no evidence for an unequivocal treatment deferral of this risk group. We retrospectively analyzed the direct effect of IV drug use on treatment outcome in 500 chronic hepatitis C patients enrolled in the Swiss Hepatitis C Cohort Study. Patients were eligible for the study if they had their serum hepatitis C virus (HCV) RNA tested 6 months after the end of treatment and at least one visit during the antiviral therapy, documenting the drug use status. Five hundred patients fulfilled the inclusion criteria (199 were IDU and 301 controls). A minimum exposure to 80% of the scheduled cumulative dose of antivirals was reached in 66.0% of IDU and 60.5% of controls (P = NS). The overall sustained virological response (SVR) rate was 63.6%. Active IDU reached a SVR of 69.3%, statistically not significantly different from controls (59.8%). A multivariate analysis for treatment success showed no significant negative influence of active IV drug use. In conclusion, our study shows no relevant direct influence of IV drugs on the efficacy of anti-HCV therapy among adherent patients.

Adherence to the Swiss guidelines for management of COPD: experience of a Swiss teaching hospital.

QUESTIONS UNDER STUDY: Swiss guidelines for the management of chronic obstructive pulmonary disease (COPD) were published in 2002. We aimed at assessing adherence to the proposed guidelines by the physicians in charge for all patients referred to our hospital for acute exacerbations of COPD over a one year period. METHODS: In a prospective observational study, data from a questionnaire and from records of all patients referred to our hospital with acute exacerbation of COPD were collected. Diagnostic steps as well as therapeutic and prophylactic interventions were reviewed. Where applicable, interventions were stratified according to proposed levels of evidence A-D. RESULTS: 45 patients in whom the diagnosis of COPD had been made before were included. Diagnosis was established by spirometry in 71%, in the remaining diagnosis was based on clinical grounds only. Non-smoking advice was given to 69%, and 16% were offered a nicotine-replacement trial (level A). Information about a disease management plan was given in 40% of the patients (level B), 22% had done a six minute walking distance test. 27% of the patients had participated in a pulmonary rehabilitation program (level A). 93% were on regular bronchodilator therapy (level B), and 56% had regular inhaled corticosteroids (level B). CONCLUSION: Confirmation of the diagnosis of COPD by spirometry is lacking in a significant number of patients. Most patients were treated with regular bronchodilators, however, relevant over-treatment with beta-adrenergic substances and overuse of inhaled corticosteroids in mild disease stages are common. Efforts for disease prevention and education as well as awareness of the potential benefits of pulmonary rehabilitation programs are still insufficient. Efforts to improve the adherence to the Swiss guidelines for the management of COPD should be intensified.