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To examine changes over a 2-year period in both the mortality rate and the causes of death in a geographically defined HIV-infected population.A database search of primary care information for the dates and causes of death for all patients documented with HIV infection and living in Southern Alberta between 1984 and 2003 was undertaken. Sociodemographic and clinical characteristics were obtained. Causes of death were then individually confirmed by reviewing the patients' hospital charts, autopsy reports, or death certificates and coded using the International Classification of Diseases, 9th Revisions. AIDS deaths were reconciled with Public Health Reports. The time span was divided into pre-highly active antiretroviral therapy (HAART) (1984–1996) and current HAART (1997–2003) periods.Between 1984 and 2003, there were 560 deaths in the 1987 individuals living with HIV infection in Southern Alberta. Of these, 436 deaths (78%) occurred pre-HAART and 124 (22%) in the current HAART period. The crude mortality rate declined from 117 deaths per 1000 patient-years pre-HAART to 24 in the current HAART period. In the pre-HAART era, 90% of all deaths were AIDS related whereas only 67% were AIDS related in the current HAART era. The leading causes of AIDS deaths were AIDS multiple causes (31%), Mycobacterium avium complex (18%), Pneumocystis pneumonia (10%) and non-Hodgkin's lymphoma (7%). The proportion of non-AIDS related deaths increased from 7% pre-HAART to 32% in the current HAART era. Accidental deaths, including drug overdose (29%), suicide (7%) and violence (3%), hepatic disease (19%), non-AIDS related malignancies (19%), and cardiovascular disease (16%) accounted for the majority of non-AIDS related deaths. No deaths directly caused by drug toxicity were found. Overall, 21% of patients who died were antiretroviral (ARV)-naïve. A total of 14% of patients dying from AIDS were ARV-naïve in contrast to 35% dying from non-HIV related conditions. Of all those dying from AIDS, 23% died<3 months after their initial diagnosis, reflecting late presentation. In the current HAART era, 87% of patients who died from AIDS were extensively treated, reflecting HAART treatment failures due mostly to multiclass drug resistance (42%), inexorable disease progression despite ARV (32%), lack of ability or interest to be maintained on a lifelong HAART programme (21%) and, rarely, drug intolerance (<1%).Deaths from AIDS-related causes have decreased significantly, but deaths from non-AIDS related conditions have increased, both as an absolute number of deaths and as a proportion of all deaths in HIV-infected patients. The increasing age of the HIV population, and the increased mean CD4 count, increased proportion of intravenous drug users, increased hepatitis B virus and hepatitis C virus coinfection rate, and increased history of smoking seen in our population also influenced the mortality rate and causes of death. These factors must also be considered in projecting future trends in mortality of an HIV-infected population.