Improved understanding of host immunity in immunocompromised patients can improve the prediction, prevention and treatment of infectious complications in this setting. Immunocompromised patients develop frequent infective/inflammatory complications, which leads to worse outcomes and can impair their quality of life. Working with well-characterised cohorts of People living with HIV (PLWH), haematopoietic stem cell transplantation (HSCT) recipients and patients with primary/secondary immune deficiencies, Sheffield BRC investigates the impact of vaccines and antimicrobial prophylaxis on disease development and progression, and treatment complications such as the development of antimicrobial resistance.

There are three primary areas of focus within this sub-theme:

1. The development and evolution of chronic lung disease (CLD) driven by recurrent infection in immunocompromised hosts (e.g. bronchiectasis, graft-versus-host disease, interstitial lung disease in HSCT/immune deficiency, and CMV-associated CLD in perinatally-acquired HIV infection). We use innovative imaging approaches (optical coherence tomography and hyperpolarised gas MRI) to examine infectious and immune complications in these cohorts, in conjunction with the Imaging & Engineering Theme.

2. The management of renal complications and bone disease in people living with HIV. Renal complications are increased in HIV patients of African heritage with variants of the APOL-1 gene, which is an active area of research within Sheffield. Bone disease will be assessed in longitudinal studies of bone health evaluated by the Sheffield FRAX score.

3. Improving vaccine efficacy in immunocompromised populations. We develop early diagnostic and predictive parameters in immunocompromised populations, identify the risks/benefits associated with preventative strategies and evaluate novel therapeutic interventions.

Aims

• To improve the length and quality of life for people living with HIV, including those of African heritage, and young adults with HIV-associated Chronic Lung Disease.

• To improve outcomes of HSCT with improved strategies to identify and prevent infectious complications.

• To improve the lives of patients with primary and secondary immunodeficiency through better understanding of underlying defects and the various prevention and treatment strategies necessary for each.