Strengthening integration of chronic care in Africa: protocol for the qualitative process evaluation of integrated HIV, diabetes and hypertension care in a cluster randomised controlled trial in Tanzania and Uganda.

INTRODUCTION: In sub-Saharan Africa, the burden of non-communicable diseases (NCDs), particularly diabetes mellitus (DM) and hypertension, has increased rapidly in recent years, although HIV infection remains a leading cause of death among young-middle-aged adults. Health service coverage for NCDs remains very low in contrast to HIV, despite the increasing prevalence of comorbidity of NCDs with HIV. There is an urgent need to expand healthcare capacity to provide integrated services to address these chronic conditions. METHODS AND ANALYSIS: This protocol describes procedures for a qualitative process evaluation of INTE-AFRICA, a cluster randomised trial comparing integrated health service provision for HIV infection, DM and hypertension, to the current stand-alone vertical care. Interviews, focus group discussions and observations of consultations and other care processes in two clinics (in Tanzania, Uganda) will be used to explore the experiences of stakeholders. These stakeholders will include health service users, policy-makers, healthcare providers, community leaders and members, researchers, non-governmental and international organisations. The exploration will be carried out during the implementation of the project, alongside an understanding of the impact of broader structural and contextual factors. ETHICS AND DISSEMINATION: Ethical approval was granted by the Liverpool School of Tropical Medicine (UK), the National Institute of Medical Research (Tanzania) and TASO Research Ethics Committee (Uganda) in 2020. The evaluation will provide the opportunity to document the implementation of integration over several timepoints (6, 12 and 18 months) and refine integrated service provision prior to scale up. This synergistic approach to evaluate, understand and respond will support service integration and inform monitoring, policy and practice development efforts to involve and educate communities in Tanzania and Uganda. It will create a model of care and a platform of good practices and lessons learnt for other countries implementing integrated and decentralised community health services. TRIAL REGISTRATION NUMBER: ISRCTN43896688; Pre-results

In Vivo Validation of a Bioinformatics Based Tool to Identify Reduced Replication Capacity in HIV-1

Although antiretroviral drug resistance is common in treated HIV infected individuals, it is not a consistent indicator of HIV morbidity and mortality. To the contrary, HIV resistance-associated mutations may lead to changes in viral fitness that are beneficial to infected individuals. Using a bioinformatics-based model to assess the effects of numerous drug resistance mutations, we determined that the D30N mutation in HIV-1 protease had the largest decrease in replication capacity among known protease resistance mutations. To test this in silico result in an in vivo environment, we constructed several drug-resistant mutant HIV-1 strains and compared their relative fitness utilizing the SCID-hu mouse model. We found HIV-1 containing the D30N mutation had a significant defect in vivo, showing impaired replication kinetics and a decreased ability to deplete CD4+ thymocytes, compared to the wild-type or virus without the D30N mutation. In comparison, virus containing the M184V mutation in reverse transcriptase, which shows decreased replication capacity in vitro, did not have an effect on viral fitness in vivo. Thus, in this study we have verified an in silico bioinformatics result with a biological assessment to identify a unique mutation in HIV-1 that has a significant fitness defect in vivo

Potential of hybrid 18F-fluorocholine PET/MRI for prostate cancer imaging

To report the first results of hybrid (18)F-fluorocholine PET/MRI imaging for the detection of prostate cancer