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Introduction: In resource-limited countries, people with disabilities seem to be particularly vulnerable to HIV infection due to barriers to accessing information and services, frequent exposure to sexual violence and social exclusion. However, they have often been left behind in the HIV response, probably because of the lack of reliable epidemiological data measuring this vulnerability. Multiple challenges in conducting good quality epidemiological surveys on people with disabilities require innovative methods to better understand the link between disability and HIV. This paper describes how the design and methods of the HandiVIH study were adapted to document the vulnerability of people with disabilities to HIV, and to compare their situation with that of people without disabilities. Methods and analysis: The HandiVIH project aims to combine quantitative and qualitative data. The quantitative component is a cross-sectional survey with a control group conducted in Yaoundé (Cameroon). A two-phase random sampling is used (1) to screen people with disabilities from the general population using the Washington Group questionnaire and, (2) to create a matched control group. An HIV test is proposed to each study participant. Additionally, a questionnaire including a life-event interview is used to collect data on respondents' life-course history of social isolation, employment, sexual partnership, HIV risk factors and fertility. Before the cross-sectional survey, a qualitative exploratory study was implemented to identify challenges in conducting the survey and possible solutions. Information on people with disabilities begging in the streets and members of disabled people's organisations is collected separately. Ethics and dissemination: This study has been approved by the two ethical committees. Special attention has been paid on how to adapt the consenting process to persons with intellectual disabilities. The methodological considerations discussed in this paper may contribute to the development of good practices for conducting quantitative health surveys on people with disabilities. [ABSTRACT FROM AUTHOR]