OBJECTIVE: To assess the impact of clinical and social factors unique to HIV-infected adults in Saskatoon, Saskatchewan, regarding the rate of CD4+ count change, and to identify factors associated with a risk of CD4+ count decline.METHODS: A retrospective longitudinal cohort study from medical chart reviews at two clinics was conducted in Saskatoon. Univariate and multivariate linear mixed effects models were used to assess the impact of selected factors on CD4+ count change.RESULTS: Four hundred eleven HIV-infected patients were identified from January 1, 2003 to November 30, 2011. Two hundred eighteen (53%) were male, mean (± SD) age was 35.6 ±10.1 years, 257 (70.8%) were First Nations or Métis, 312 (80.2%) were hepatitis C virus (HCV) coinfected and 300 (73.3%) had a history of injection drug use (IDU). In univariate models, age, ethnicity, HCV, IDU, antiretroviral therapy and social assistance were significant. Using ethnicity, HCV and IDU, three multivariate models (models 1, 2, 3) were built due to high correlation. First Nations or Métis ethnicity, HCV coinfection and a history of IDU were associated with significantly lower CD4+ counts in multivariate models. Older age and social assistance were associated with significantly lower CD4+ counts in models 1 and 3. Age was marginally significant in model 2 (P=0.055). Not prescribed antiretroviral therapy was associated with a significantly negative CD4+ count slope in all multivariate models.CONCLUSION: The unique epidemiology of this HIV-infected population may be contributing to CD4+ count change. Increased attention and resources focused on this high-risk population are needed to prevent disease progression and to improve overall health and quality of life.