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REACH: Russian European Alliance for research among women, Children and adolescents impacted by HIV, TB and HCV

Periodic Reporting for period 3 - REACH (REACH: Russian European Alliance for research among women, Children and adolescents impacted by HIV, TB and HCV)

Reporting period: 2021-01-01 to 2021-06-30

Pregnant women, children and adolescents are priority populations in the global public health response to the epidemics of HIV, TB and HCV. The global health goals of ending AIDS, reducing TB deaths and new HCV cases by 90% by 2030 can only be realized if the health needs of these populations are considered and targeted research undertaken to optimize innovations in diagnostics and treatment. REACH builds on a long-standing collaboration between European clinical research networks with leading collaborators from 4 centres of excellence in Siberian, North-western and Central districts of the Russian Federation.
Within REACH, we conducted studies on epidemiology, management and outcomes of children, adolescents and pregnant women with HIV, HCV and TB, TB diagnostics and HCV treatment practices in children in Russia. REACH partners harmonised research methods and conducted training courses on HIV, TB, HCV and research methodology. We developed future studies on cardiovascular disease among children living with HIV, TB diagnostics and new HCV treatment for children thus building a strong foundation for collaborative research with broad and long-lasting impact. Working closely with young people living with HIV, we supported youth activity groups for a meaningful patient and public involvement in the research studies and training activities. Overall, REACH promoted collaborative research in maternal and child health in Europe and Russia and strenghtened capacity for further research beyond 2021.
Early outputs from REACH studies in children living with HIV include paediatric HIV cascade of care analyses highlighting poorer outcomes in patients diagnosed with HIV during adolescence (aged 10-19 years) compared to those diagnosed in childhood (aged<10 years). Those diagnosed in adolescence were highlighted as a key population who would benefit from targeted interventions..

The REACH paediatric work on hepatitis C reports on the increasing access direct acting antivirals in adolescents including those with HIV/HCV coinfection, , and highlights the need to expand the access for younger children. Our work on tuberculosis includes pooling individual level data on ~4000 children referred for tuberculosis screening and care, allowing to assess the performance of tuberculin skin test compared to Diaskintest.

The REACH work on pregnant women and their infants demonstrates that the overall vertical transmission rate has decreased to 1.8% in 2017-2019. Among the small number of pregnancies where vertical transmission occurred, around half of women were diagnosed in pregnancy or at delivery. Overall, the proportion of pregnant women with HIV who have moderate to severe immunosuppression and thus at high risk of developing serious illnesses ranged from 7-16% across participating centres. There remains a substantial HCV coinfection burden among pregnant women living with HIV, predominated by women with an injection drug use history. These findings highlight the need for improvement of HIV case finding among pregnant late presenting women and call for timely diagnosis and treatment of chronic HCV in women of reproductive age and HCV screening of their infants.
Young people born with HIV and surviving into adulthood are at risk of premature cardiovascular disease, which may result in myocardial infarction or stroke. With partners in Irkutsk, we assessed the feasibility of using ultrasound to measure carotid intima-media thickness, providing an opportunity for earlier detection of cardiovascular disease in this population.
Our work with the team at the Republican Hospital of Infectious Diseases on neurocognitive assessment showed that a quarter of children living with HIV may have neuroradiological abnormalities with possible impossible impact on cognitive function. This was associated with older age at treatment initiation, calling for earlier diagnosis and treatment for children infected with HIV.
Over the life-time of the REACH project, over 500 healthcare professionals have been trained on the clinical management and treatment of children, adolescents and pregnant women with HIV, TB and/or HCV, molecular epidemiology and research methodology through residential & online courses.. New clinical and research training modules were developed. Detailed standard operating procedures were produced to enable the data merger of individual patient level data across the three disease areas as well as COVID-19/SARS CoV-2. Laboratory training was undertaken for the joint future collaborative study on TB biomarkers in children.

REACH has engaged with young people living with HIV in Russia and created youth activity groups
(Project Next Generation+) to ensure meaningful patient involvement in the research and training activities. The PNG+ members participated in REACH meetings and training courses, created visual materials for the REACH project and developed tools to help communicate research findings to youth communities and care givers affected by HIV.
Our priorities focus on maternal and child health. Our results address important research gaps regarding risk of onward transmission, disease progression, ART toxicity, drug resistance, comorbidities and coinfections, and contribute to capacity strengthening in key areas to advance future research, treatment and prevention of HIV, HCV and TB.

To date, 7 abstracts have been accepted and most have already been presented at international conferences (see https://alliance-reach.eu/). Further analyses will continue over the next year.

There are eight ongoing and planned manuscripts addressing priority research questions for children and pregnant women affected with HIV, HCV and TB. In addition, data from the Russian data merger will contribute to the planned Europe-wide paediatric and pregnancy analyses to be conducted from this year onwards (see https://penta-id.org/hiv/eppicc/) to inform public health and clinical management policies for children and pregnant women affected with HIV, HCV and TB and impact of COVID-19 on HIV outcomes.
Building on the collaborative research work in REACH, four research protocols have been developed to enable future prospective studies on diagnostic TB biomarkers, advanced imaging for early recognition of atherosclerosis, neurocognitive health in HIV-infected youth and new direct antiviral treatment of HCV in children.

Multi-modal Russian language training materials on HIV, HCV and TB, molecular epidemiology and research methods have been developed by international teams to provide up-to-date information to health care professionals. The Russian/European School established by the Republican Hospital of Infectious Diseases, St Petersburg and Penta will continue to run training sessions for 80+ AIDS centres in Russia.
The established youth group in Russia will continue their work in collaboration with a newly formed UK-based group, providing ongoing involvement of patient community in paediatric research studies.
During the life-time of the project, REACH consortium improved evidence bases to prevent, diagnose, treat and care for pregnant women and children living with HIV, TB and HCV and built a strong west-east research collaboration to identify effective interventions for reduction of the morbidity and mortality associated with these infections over the long term.
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