INTRODUCTION: In settings with low literacy levels ensuring that participants are fully-informed before they consent to participate in clinical trials is a challenge. We explored the experiences and concerns of key actors in the informed consent process in two HIV clinical trials. METHOD: Semi-structured interviews were conducted with 46 respondents including trial participants, research study team and research ethics committee members about their experiences during the informed consent process. Three focus group discussions were conducted with 14 Community Advisory Board (CAB) members and 17 trial participants. Data were analysed to identify key themes. FINDINGS: The consent process was highlighted as an important procedure by all the key actors however each group had a particular area of emphasis. Signing a consent form was given importance by research team and ethics committee members, because it provided documented evidence of a participant's willingness to join a clinical trial. Participants did not welcome the presence of a witness for a non-literate participant because understanding study information was not closely related to an ability to read and write. CONCLUSION: This study's findings indicated that obtaining a volunteer's signature or thumbprint on a consent form did not necessarily mean that the participant was fully-informed about the information relevant to their taking part nor that they understood all the information shared with them. Informed consent requires sufficient time in the research process to have staff trained well enough before research begins. Ensuring and gaining informed consent should be understood and treated as a relation-centred, dynamic supportive process throughout the duration of a research study.