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Objective: To assess the impact of HIV-1 infection on mortality over five years in a rural Ugandan population., Design: Longitudinal cohort study followed up annually by a house to house census and medical survey., Setting: Rural population in south west Uganda., Subjects: About 10,000 people from 15 villages who were enrolled in 1989-90 or later., Main Outcome Measures: Number of deaths from all causes, death rates, mortality fraction attributable to HIV-1 infection., Results: Of 9777 people resident in the study area in 1989-90, 8833 (90%) had an unambiguous result on testing for HIV-1 antibody; throughout the period of follow up adult seroprevalence was about 8%. During 35,083 person years of follow up, 459 deaths occurred, 273 in seronegative subjects and 186 in seropositive subjects, corresponding to standardised death rates of 8.1 and 129.3 per 1000 person years. Standardised death rates for adults were 10.4 (95% confidence interval 9.0 to 11.8) and 114.0 (93.2 to 134.8) per 1000 person years respectively. The mortality fraction attributable to HIV-1 infection was 41% for adults and was in excess of 70% for men aged 25-44 and women aged 20-44 years. Median survival from time of enrollment was less than three years in subjects aged 55 years or more who were infected with HIV-1. Life expectancy from birth in the total population resident at any time was estimated to be 42.5 years (41.4 years in men; 43.5 years in women), which compares with 58.3 years (56.5 years in men; 60.5 years in women) in people known to be seronegative., Conclusions: These data confirm that in a rural African population HIV-1 infection is associated with high death rates and a substantial reduction in life expectancy.