over time. Separate estimates are made for urban and rural prevalence and then combined to produce a national estimate. The epidemic model uses four parameters to determine the prevalence trend over time: the start year of the epidemic, the initial force of infection, the proportion of the population at risk of infection and the rate of replenishment of the population at risk when it is depleted by AIDS deaths. EPP generates 50,000 to 200,000 epidemic curves by randomly selecting values of these four parameters from plausible distributions. Each of these curves is tested to see how well it fits the surveillance and survey data. A sample of curves is drawn from the full set with the likelihood of selection proportional to the goodness of fit. The result is a most likely curve that provides a point estimate of prevalence in each year and a range around the point estimate. The estimates of adult HIV prevalence are used in the AIDS module of Spectrum [8] to estimate the other indicators of interest such as the number of people living with HIV, new infections, AIDS deaths, need for treatment and the number of orphans. HIV prevalence among adults 15–49 is combined with information on the age and sex distribution of prevalence from the national survey to estimate the distribution of prevalent adult infections by age and sex. The trend in prevalence is combined with information on the distribution of time from infection to AIDS death from cohort studies to estimate the number of new adult infections by age and sex. New infant infections are estimated from prevalence among pregnant women and the rate of mother-to-child transmission, which is dependent on infant feeding practices and the coverage of prophylaxis with ARVs. New infections progress over time to a symptomatic stage where ART is needed. The rate of progression from infection to AIDS death for adults is a distribution drawn from cohort studies in sub-Saharan Africa [9]. The median time from infection to AIDS death without treatment is 11 years. Eligibility for ART is assumed to occur at a median of three years before AIDS death [10]. Those who receive first- and/or second-line ART experience extended survival. In Botswana, program data are available on the proportion of ART patients who are known to be alive by time since the initiation of therapy. As of December 2007 information is available on 75,393 patients. These data show that after 12 months, 91.3% of ART patients are known to be still alive, and after five year 86% of ART patients are still alive. These rates mayoverstate the true survival since some of those who were lost to follow-up (i.e. their status is unknown) have probably died. The UNAIDS Reference Group on Estimates, Models and Projections assumes that for most new programs the annual survival rates are 85% for the first year on ART and 95% for subsequent years [10]. However, the first year survival is likely to be lower in new programs with low ART coverage since most patients get started on ART very late, with low CD4 counts. When coverage is high as in Botswana patients are identified as being in need earlier and generally start ART at higher CD4 counts which should result in better first year survival. People at any stage are subject to non-AIDS mortality at the same rates as those who are not infected. The progression of children from infection to AIDS death is modeled as a double Weibull curve fitted to longitudinal data [11]. AIDS and non- AIDS orphans are estimated from the number of adult deaths each year, the fertility history of those who die and the rates of child survival. Spectrum estimates the uncertainty around the estimate of each indicator by using a Monte Carlo approach. One thousand projections are calculated using different prevalence curves provided by EPP and drawing random values of other key parameters (such as the progression time to AIDS death, and the effectiveness of ART) for each projection. The results are analyzed HIV in Botswana Table 1. Key HIV/AIDS Indicators and Plausibility Bounds, 2007 Indicator HIV Adults+Children HIV Adults 15+ HIV population-Children Prevalence Adult New HIV infections-Adult New HIV Infections-Children Annual AIDS deaths-Adult Annual AIDS deaths-Children Need for ART-Adult (15+) Need for ART-Children Mothers needing PMTCT AIDS orphans Value in 2007 Plausibility Bounds 330,000 311,000 19,561 25.7 18,000 890 7,400 790 120,000 7,400 15,000 90,000 318000–345000 299000–325000 18000–21000 24.8–26.7 12000–26000 810–980 5000–11000 600–1020 101000–136000 6800–7800 13000–16000 76000–103000 doi:10.1371/journal.pone.0003729.t001 to produce 5% and 95% plausibility bounds around each point estimate. (These are not true confidence intervals since the errors around the input assumptions are not measured directly and we cannot include all sources of error.) Results Results for key HIV/AIDS indicators are shown in Table 1. The plausibility bounds for prevalence and number of adults infected are narrow because the national survey provided an accurate estimate of the level of infection in 2004. Bounds for other indicators rely on additional assumptions, such as the progression period from infection to death and the effects of ART and PMTCT and, therefore, are wider. Prevalent Adult HIV Infections HIV trends at antenatal surveillance sites are shown for urban and rural sites in Figure 1. The best fitting curves to these data suggest that HIV prevalence has declined somewhat in urban areas since 2000 and has remained stable in rural areas. These curves need to be adjusted to match the national population survey Figure 1. HIV prevalence among women attending antenatal clinics, 1991–2007. Data from urban clinics (Figure 1a) and rural clinics (Figure 1b) are shown in the gray lines. The smooth curve produced by EPP is shown in the dark dashed line for each region. doi:10.1371/journal.pone.0003729.g001 PLoS ONE | www.plosone.org 2 November 2008 | Volume 3 | Issue 11 | e3729