# Considerations in planning a controlled human infection model in at-risk groups in sub-Saharan Africa: the case for pneumococcal challenge in people living with HIV in Malawi and a report of stakeholder consultation

## TL;DR

This paper discusses the ethical and practical considerations of using controlled human infection models in high-risk populations like people living with HIV in Malawi.

## Contribution

The paper proposes a framework for safely conducting pneumococcal challenge studies in people living with HIV in sub-Saharan Africa.

## Key findings

- Most CHIMs focus on healthy young adults, who differ from high-risk populations like those with HIV.
- A pneumococcal carriage model in people living with HIV in Malawi is proposed as a case example.
- Safety, ethics, and stakeholder consultation are emphasized for CHIMs in vulnerable populations.

## Abstract

Controlled human infection models offer a unique opportunity to understand infectious disease pathogenesis and have accelerated vaccine development and evaluations in malaria and typhoid. One major limitation of most CHIMs is that they are typically conducted in healthy young adults who are generally the population least affected by infectious disease, and who exhibit distinct disease profiles to more at-risk populations such as people living with HIV, young children, and older adults. However, the added value of studying these populations with high relevance is only desirable if it can be done safely, robustly and acceptably. We present a framework to guide the conduct of a controlled human infection model in people living with HIV using a case-example of an experimental human pneumococcal carriage model in a setting of high disease-burden and transmission.

Controlled human infection models (CHIMs) are a research method in which an infection is safely introduced into volunteer participants to better in order to understand the infection and test vaccines against it. These models are more efficient than traditional clinical studies because they require fewer participants. Most CHIMs have focused on healthy young adults, who are not the ones most affected by infectious diseases and have a distinct infection profile and vaccine response compared to population with a greater burden of infectious disease such as older adults and people living with HIV. Recently researchers have started to include these high-burden populations in CHIMs but safety and ethics are critical considerations before embarking on such studies. We propose a framework for safely and ethically conducting CHIMs in people living with HIV in order to advance research in this key population. We use a case example of a CHIM of pneumococcal carriage in the nose of people living with HIV in Malawi.