Acceptability of advanced Controlled Human Infection Models: The case of a pneumococcal challenge in people living with HIV and mycobacterial challenge with Bacillus Calmette Guerin in Malawi.

Controlled Human Infection Models (CHIM) in which volunteers are experimentally exposed to pathogens are used to study pathogenesis and down select among treatment and vaccine candidates. Scientifically, CHIM studies are best conducted among at-risk populations in which the infection is endemic, and who are likely to benefit from new interventions tested. Ethically, the perspectives of these communities should be carefully considered in designing such research. CHIM studies are often conducted among healthy adults, but we wished to understand study participant's and community views on conducting CHIM studies in groups other than healthy adults, particularly people living with HIV (PLHIV). We also wished to explore community perceptions of a tuberculosis CHIM (TB CHIM), initially using Bacillus Calmette Guerin (BCG) as a safe intermediate step. We conducted fourteen focus group discussions (FGD) and eight in-depth interviews (IDI) among a wide range of stakeholders including participants, health workers, community advisory groups, religious leaders and medical opinion leaders in Malawi. Discussions and interviews were recorded, transcribed and analysed using thematic and framework analysis. Four themes were described in the data, showing engaged stakeholder acceptance of CHIM studies, and confidence in the research practice and motivation. In the specific examples discussed in this work at-risk populations specifically PLHIV and complex pathogens specifically TB-CHIM, there was concern for safety, proper consent and community consultation. In addition, cultural views on gender roles in Malawi, tissue sampling and residential stays for research study were discussed. Overall, there was support for CHIM among PLHIV, and CHIM working through a BCG CHIM towards safe TB CHIM in future. Appropriate safety caveats and regulatory measures were suggested. Advice on wide, public awareness campaign methods was offered to researchers.