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Advances in therapy have allowed children with perinatal HIV infection in the United States to survive into adolescence. We sought to describe the disease status of a large cohort of such children and identify predictors of their current CD4 count and HIV viral load (VL).The Pediatric HIV/AIDS Cohort Study AMP Protocol is an ongoing prospective study conducted at 15 sites in the United States. Between 2007 and 2009, we enrolled a population-based sample of 451 children with perinatal HIV who were 7-16 years of age at entry.The median age of subjects at entry was 12.2 years, 53% were female, 70% were African-American, and 24% Hispanic. Their median entry CD4% was 33%, and 78% had a CD4% ≥25%; 68% had a suppressed VL. The more recent birth cohorts (1994-2002) had a significantly higher CD4% over time than the earliest birth cohort (1991-1993). The significant independent predictors of a higher CD4% at entry were a suppressed entry VL, a higher nadir CD4%, and starting antiretroviral therapy at a younger age. The mean CD4% at entry for children with a nadir CD4% ≥25% was 9.5% higher than for those with a nadir CD4% <15% (P < 0.001). Independent predictors of a suppressed entry VL were membership in a recent birth cohort, male gender, highly active combination antiretroviral therapy use at entry, and fewer prior antiretroviral therapy regimens.Most children with perinatal HIV maintain virologic suppression and good CD4 values. Earlier treatment results in better immune outcome.