Host factors can have important consequences for HIV risk and disease progression. Two separate projects relevant to Aboriginal populations in Manitoba were undertaken. The Solvent Use Project investigated solvent use in Winnipeg through an interdisciplinary multi-phase approach that integrated community based research and basic science. From interviews with solvent users and key informants we learned that solvent users experience many health and social disparities. We demonstrated that there is support within the community to work with solvent users and study solvent use further. The HLA-B*35 Project aimed to identify the diversity of HLA-B*35 allele subtypes, in HIV+ patients that presented to care between 2007 and 2010 in Manitoba. We observed 11 distinct HLA-B*35 allele subtypes. Case studies reflected the overrepresentation of Aboriginal people infected with HIV in Manitoba, and the pressing issues of either late presentation to care or rapid disease progression within patients who are HLA B*35.