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In August 2005, the World Health Organization declared the tuberculosis (TB) epidemic in Africa to be a regional emergency. Current TB-control measures are failing, largely as a result of the human immunodeficiency virus (HIV) epidemic. Evaluation of additional control interventions requires detailed understanding of the epidemiological relationship between these diseases at the community level.We examined age- and sex-specific trends in TB notifications and their association with the prevalence of HIV infection in a peri-urban township in South Africa during 1996–2004. Denominators for TB notifications were derived from population census data. The local TB-control program used the World Health Organization directly observed treatment, short-course (DOTS) strategy.TB notification rates increased 2.5-fold during the period, reaching a rate of 1468 cases per 100,000 persons in 2004 (P = .007, by test for trend); the estimated population prevalence of HIV infection increased from 6% to 22% during the same period. After stabilization of prevalence of HIV infection, the TB notification rate continued to increase steeply, indicating ongoing amplification of the TB epidemic. In 2004, at least 50% of children aged 0–9 years who developed TB were HIV infected. Annual TB notification rates among adolescents increased from 0 cases in 1996–1997 to 436 cases per 100,000 persons in 2003–2004, and these increases were predominantly among female. However, 20–39-year-old persons were affected most, with TB notification rates increasing from 706 to 2600 cases per 100,000 persons among subjects in their 30s. In contrast, TB rates among persons aged >50 years did not change.HIV infection is driving the TB epidemic in this population, and use of the DOTS strategy alone is insufficient. TB notifications have reached unprecedented levels, and additional targeted, age-specific interventions for control of TB and HIV infection in such populations are needed.