Periodic Reporting for period 1 - CARE (COMMON ACTION AGAINST HIV/TB/HCV ACROSS THE REGIONS OF EUROPE)
Reporting period: 2019-01-01 to 2019-12-31
Human immunodeficiency virus, HIV
An estimated 2.3 million people are living with HIV in the WHO European Region today. In 2017, nearly 160 000 people were newly diagnosed with HIV in the WHO European Region, the majority (82%) of them being from the eastern part of the Region.
Although most HIV patients under modern antiretroviral therapy (ART) respond well to therapy, a minority still experience virological failure or have to change their successful regimen due to drug resistance, toxicity, drug-drug interactions or comorbidity.
Recently, the modern class of antivirals called “integrase strand transfer inhibitors” (InSTI) is being introduced into low/middle-income countries, requiring specific surveillance particularly in eastern Europe, where a specific viral population is present (including the HIV-1 A6 variant).
TB causes 10.4 million new cases globally. With just over 280 000 cases reported in 2017, TB remains a major public health problem in the WHO European Region.
TB diagnosis is difficult and, more significantly, reliable prognostic markers (i.e. cure, relapse, failure, etc.) are missing. Multi-drug resistant TB (MDR-TB) requires long, expensive, often ineffective treatments. Patients from eastern Europe show specifically high rates of second-line MDR-TB.
Hepatitis C, HCV
The size of the HCV-infected population in the eastern region of Europe is around 14 million, and in combination with excessive alcohol consumption is a major cause of excess morbidity and mortality.
With the availability of direct acting oral anti-HCV drugs (DAA), communitywide eradication of HCV appears possible, but to define an optimal treatment strategy under public health perspective is necessary.
Why is it important for society?
CARE activities will define tools, paradigms and interventions aiming at improving clinical care and treatment outcomes and reducing the burden of the three diseases in the short, medium and long term.
What are the overall objectives?
The overall objective of CARE is to analyse and combat the HIV, TB and HCV epidemics across the European Region with a specific focus on the Russian Federation (Fig. 1).
The short-term objective of the project within the 2-year framework is to generate novel research findings with potential short term application on the most relevant issues, based on existing biological material and data already collected by the consortium partners as well as on new samples and data gathering.
The longer-term objective of the CARE project is to implement the necessary collaborative research infrastructure to sustain and fuel the established scientific cooperation, allowing the expansion of activities beyond the funding frame.
This allowed the scientific work to start both in labs, on already and newly collected samples, and on data analysis.
Training sessions, with Russian young researchers coming to Europe, have already been held (Fig. 3).
Four scientific papers have been produced and five posters presented at international conferences.
The conference “Joint efforts against infectious diseases: HIV, TB, HCV”, planned in Moscow, 27th January 2020, is being co-organised with EU and Russian Federation Ministries, within a joint Programme Committee, aiming at communicating the project’s objectives and first results to a highly relevant audience of stakeholders (Fig. 4).
Details of major results obtained so far are given below.
With regard to TB diagnostic and MDR-TB biomarkers:
• Preliminary analysis of the results from urine samples yielded a high number of variables associated with TB, that permitted to distinguish TB patients not only from healthy subjects but also from patients with other pulmonary infections.
• The analysis of TB trans-renal DNA by our methodology appears successful for very low DNA concentration.
As per effective MDR-TB management based on TB genotyping:
• A first version of the decision making support tool for the choice of second line therapy in case of suspected MDR-TB has been implemented showing improvement in drug resistance prediction
• DNA samples from MDR-TB patients under the new bedaquiline treatment have been isolated and are under investigation to clarify the molecular basis of drug resistance.
Regarding HIV molecular epidemiology and new treatment strategies in the region:
• The Eastern European Database for molecular HIV epidemiological analysis has been set-up
• A high-through put sequencing assay for HIV-1 A6 strains has been established
• Samples from HIV+ A6 patients have been shipped from Russia to Europe and the creation of recombinant A6 viruses has started.
About host genomic effects on clinical outcome:
• Existing platform of 10000 HIV+ patients have already been analysed
• Over 2800 patients have been recruited in Georgia, Ukraine and Russia for the set-up of a prospective HIV Eastern European cohort for human genomic studies, recruitment in progress.
With regard to prioritisation of DAA treatment in HCV infected individuals
• Data on 122466 HCV-infected patients have been collected from Georgia, Italy, Sweden and the EuroSIDA study, thus establishing a larger than expected multicenter HCV datalake for retrospective studies.
• 1020 HIV/HCV co-infected persons enrolled to set-up a large multicenter prospective cohort of HIV/HCV co-infected persons from Russia and Ukraine, recruitment in progress.
The proposed methods for early TB urine based diagnosis so as the biomarkers for early identification of MDR-TB will be pivotal, innovative result with the potential to favorably impact the burden of the whole TB epidemic.
Personalised MDR-TB treatment based on TB genotypic analysis, together with the groundbreaking innovation of a machine learning tool to support clinical choice will increase TB cure rates.
The eastern European database of HIV patients data and the Strategic Plan for HIV molecular epidemiology surveillance are ambitious and novel tools that will support targeted public health interventions.
Advances in the study of Russian HIV variants, and the adaptation to them of diagnostic tools will increase treatment success rate in Russia.
Understanding the role of host genetic variants will allow for personalization of treatment approach as this area matures.
Overall CARE will contribute to decreasing the burden of HIV disease.
Comparative study of prioritisation strategies for HCV curative DAA medications will be of the highest relevance for European healthcare policies.
Finally, CARE large cohorts and data collections have the potential to be exploited for prospective and retrospective studies, thus attracting funding and contributing to the European competitiveness.