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To estimate the burden of HIV disease in Uganda and the effect of HIV/AIDS control programmes to mitigate it.Mathematical modelling and projecting using surveillance and census data.Using antenatal clinic surveillance (1986–2002) and a recent population-based survey (2004–2005) data, we modelled the adult national HIV prevalence over time (1981–2004), and kept prevalence constant at 6.4% for the years 2004–2010. Using Spectrum software and census data, we estimated the national burden of HIV disease and the effect of selected HIV-related prevention and treatment programmes.In 2005, we estimated that there were 135 300 new HIV infections (adult HIV incidence 0.96%), 691 900 asymptomatic prevalent infections, 88 100 AIDS cases, and 76 400 AIDS deaths. An estimated 647 000 (80%) HIV-infected adults were unaware of their infection; one third of all adult deaths were HIV related. As a result of population growth, by 2008 a similar number of people will be HIV infected (1.1 million) as during the peak of the epidemic in 1994. Although antiretroviral therapy (ART) coverage is expected to rise from 67 000 (2005) to 160 000 (2010), the number of persons needing but not receiving ART will decrease only slightly from 127 600 (2005) to 111 100 (2010). The use of single-dose in 2005 nevirapine probably averted only 4% of the estimated 20 400 vertical infections.HIV/AIDS continues to be a leading cause of adult disease and death in Uganda. Universal ART access is probably unachievable. With the absolute burden of HIV disease approaching the historic peak in the early 1990s, more effective prevention programmes are of paramount importance.