In developed countries, 2 patterns of symptomatic infection have been recognized in children who are not treated. Some children become symptomatic quickly and die before 4 years of age, with a median age of death of 11 months (15–20%, termed rapid progressors). The majority (80–85%) of untreated children, on the other hand, have delayed onset of milder symptoms and survive beyond 5 years of age (termed slow progressors). Only a minority of patients remain asymptomatic by 8 years. Clinical and laboratory factors associated with poor prognosis include being born to mothers with low CD4+ counts or high viral load (ie, >100,000 copies/mL), high virus copy number in the cord blood, and early manifestation of symptoms (opportunistic infections, encephalopathy, severe wasting, and hepatosplenomegaly). Use of HAART has substantially reduced both mortality and morbidity and improved quality of life in HIV-infected children. Children with HIV infection acquired through blood transfusion tend to have a prolonged asymptomatic period. In the United States, mortality in HIV-infected children has declined from 7.2 per 100 person years in 1993 to 0.8 per 100 person years in 2006. In resource-limited developing countries, before the use of ARDs, the prognosis is much worse with one study showing 89% of the infected children having died by 3 years of age, 10% having been in HIV disease category B or C, and only ∼1% having remained without HIV symptoms. With availability of ARDs to some developing countries, the prognosis is significantly improving. Recent studies from South Africa showed that implementation of a national antiretroviral treatment program resulted in 1 year and 3 year mortality rates of 4.6 and 7.7%, respectively.